Pharmacokinetic analyses using absorption kinetics in low-alcohol dose cases of drunken driving

In Japan, low-alcohol dose cases of drunken driving, where drivers drink just before getting behind the wheel, are increasing for expert witnesses since the penalties for drunken driving have become stricter. Widmark’s equation has generally been used for the pharmacokinetic analysis of blood alcohol concentration, which encompasses the one-compartment model with zero-order elimination kinetics but ignores absorption kinetics. We therefore propose that the formula might not be applicable to the analysis of low-alcohol dose cases of drunken driving because the issue is focused on the absorption phase. In this paper, we present two representative low-alcohol dose cases, which were analyzed using the one-compartment model with first-order absorption and zero-order elimination kinetics. This formula is thought to be more suitable and useful for medicolegal practice than Widmark’s formula.     

Characteristics of sauna deaths in Korea in relation to different blood alcohol concentrations

Although the benefits of sauna bathing have been demonstrated in epidemiological studies, sauna deaths have been reported. The aim of this study was to determine the demographic and forensic characteristics associated with different blood alcohol concentrations (BACs) in sauna deaths in Korea. In this retrospective analysis, data were collected from a nationwide pool in Korea between January 2008 and December 2015 to determine the role of alcohol intoxication in sauna deaths based on the subjects’ BAC and to evaluate the demographic and forensic characteristics associated with different BACs. One hundred and three deaths were classified into 2 groups: the non-intoxication (NI) group (BAC,<0.08%; n =?27) and the intoxication (I) group (BAC,≥0.08%; n =?76). Demographic and forensic characteristics were compared between the groups using a multinomial logistic regression analysis. The proportions of decedents who were male (odds ratio: 17.4, 95.0% confidence interval: 3.8–79.8) and in a prone position at the scene of death (odds ratio: 11.3, 95.0% confidence interval: 2.1–60.1) were significantly higher (P <?0.001 and P <?0.05, retrospectively) in the I group than in the NI group. However, no significant differences were observed with respect to obesity, coronary artery narrowing, and liver pathology. Sauna deaths exhibited different characteristics according to BACs detected at autopsy. The differences in sauna deaths between the I and NI groups may have implications for the targeted prevention of sauna deaths associated with alcohol consumption.     

Ultra-rapid rate of ethanol elimination from blood in drunken drivers with extremely high blood-alcohol concentrations

The rate of alcohol elimination from blood was determined in drunken drivers by taking two blood samples about 1 h apart. These cases were selected because the individuals concerned had reached an extremely high blood-alcohol concentration (BAC) when they were apprehended. This suggests a period of continuous heavy drinking leading to the development of metabolic tolerance. Use of double blood samples to calculate the elimination rate of alcohol from blood is valid provided that drunken drivers are in the post-absorptive phase of the BAC curve, the time between sampling is not too short, and that zero-order elimination kinetics operates. Evidence in support of this came from other drunken drivers in which three consecutive blood samples were obtained at hourly intervals. The mean BAC (N = 21) was 4.05 g/l (range, 2.71–5.18 g/l), and the average rate of alcohol elimination from blood was 0.33 g l⁻¹ h⁻¹ with a range of 0.20–0.62 g l⁻¹ h⁻¹. The possibility of ultra-rapid rates of ethanol elimination from blood in drunken drivers having extremely high BAC deserves to be considered in forensic casework, e.g., when retrograde extrapolations and other blood-alcohol calculations are made. The mechanism accounting for more rapid metabolism is probably related to induction of the microsomal enzyme (CYP2E1) pathway for ethanol oxidation, as one consequence of continuous heavy drinking. However, the dose of alcohol and the duration of drinking necessary to boost the activity of CYP2E1 enzymes in humans have not been established.     

The estimation of blood alcohol concentration

Expert witnesses and others involved in toxicology are frequently asked to perform retrograde extrapolation of blood alcohol concentration (BAC) or to estimate BAC based on a proposed drinking scenario. Although many individuals are reluctant to perform these calculations and some jurisdictions expressly prohibit them, a significant number of practitioners routinely estimate BAC based on this type of calculation, using as a basis the fundamental work of Widmark. Although improvements to the Widmark formula and other data pertaining to the pharmacology of alcohol have been published, these improvements are frequently ignored when estimating BAC. This article summarizes five published models for the estimation of BAC and proposes a sixth model that incorporates recent data on the rate of absorption of alcohol from the GI tract into the existing five models. The five improved models can be computerized and used to construct comparative snapshots of the BACs calculated by the different algorithms. This will allow practitioners to provide a more balanced picture of the variability in BAC calculations.     

Toxicology,circumstances and pathology of deaths from acute alcohol toxicity

Alcohol consumption makes a large contribution to premature mortality. In order to extend our understanding of the characteristics, circumstances, toxicology and pathology of alcohol toxicity deaths, all cases presenting to the Department of Forensic Medicine Sydney between 1/1/1997–31/12/2011 with blood alcohol concentrations (BACs) ≥0.300 g/100 ml and where the direct cause of death was acute alcohol toxicity were retrieved (n = 83). The mean age was 47.2 yrs and 77.1% were male. The majority (81.9%) of deaths occurred in a home environment, and did not vary across month or day of the week. In 91.6% of cases, a history of alcoholism or heavy alcohol consumption was reported. None were in any form of substance dependence treatment at the time of death. The mean BAC was 0.420 g/100 ml (range 0.300–0.741 g/100 ml). In 33.7% of cases, other substances were detected, predominantly diazepam (28.9%). BACs did not vary significantly by gender, age or BMI. Urine/BAC ratios of >1.25 were seen in 6/43 cases where both samples were available. Cardiac disease was noted in 75.9% of cases and hepatic disease in 91.6%. The only alcohol-related organic brain syndrome pathology identified at autopsy was vermal cerebellar degeneration.     

"Cognac alibi" as a drunk-driving defense and medico-legal challenge

Some drivers with positive forensic ethanol analyses, offer an explanation that they consumed alcohol a short time before a traffic accident or after driving. In medico legal practice this is commonly known as hip-flask defense, but to us as "cognac alibi" defense. In these cases, the lawyers require the medico legal experts to offer as much information as possible so that the court may come to the most reliable conclusions about the driver's blood alcohol concentration at the moment of the traffic accident (BAC(Acc)). At the Institute of Forensic Medicine our own analytical approach was established to study this medico legal problem. It consists of three inter-related phases in which it combines the obtained BAC values, with testimonies of the drunk driving suspect andalso witnesses. A specific algorithm was designed for calculating absorption and elimination of consumed alcohol. All the above-mentioned elements and blood-ethanol values calculated according to Widmark's method were inserted into appropriate cells of MS Excel software in order to calculate BAC in the function of time. The result is a relevant analysis of the drunk driving suspect's BAC in 5-minute intervals, as well as a graphic representation in chart form.     

Cycling under the influence of alcohol-criminal offenses in a German metropolis

Introduction

Real or simulated cycling tests under the influence of alcohol might be biased by laboratory settings. Accident analyses consider incidents with injuries only. Herein, criminal offenses consisting of drunk cycling are evaluated in detail to fill this gap.

Material and methods

All police-recorded cases of cycling under the influence of alcohol that took place in Düsseldorf, Germany, from 2009 to 2018 were identified. A total of 388 respective prosecutor’s files were available for analyses.

Results

Mean blood alcohol concentrations were approximately 2 g/kg in both men and women. Men were overrepresented (6:1). Almost 60% of the cases were recorded between Friday and Sunday (the “weekend”). The average blood alcohol concentration (BAC) at night (01:00–05:59) was 0.39 g/kg lower than that during the day (06:00–17:59). Drinking after cycling allegations appear almost irrelevant among (German) cyclists. On average, the legal outcomes show 33 daily rates (median: 30). Additionally, the presented data raise doubts about whether the utilized medical tests or the ways in which they are carried out reliably discriminate between different grades of intoxication. Negative tests did not exclude high BACs, nor did positive tests correlate well with BACs.

Discussion/Conclusion

In practice, CUI is seen with BACs above 1.60 g/kg in most cases. BACs below 1.60 g/kg either seem to be a minor problem or they have been incompletely addressed thus far. In summary, to be prosecuted, drunk cyclists have to ride their bikes in either a highly insecure or rude manner or they must cause an accident.

     

Pilot performance with blood alcohol concentrations below 0.04%.

The effects of a low (less than 0.04%) BAC on pilot performance were investigated in a series of four experiments in which pilots flew a light aircraft simulator under alcohol and placebo conditions. The mean BACs of subjects when starting and finishing the test sessions were 0.037% and 0.028%, respectively. Two of the experiments involved demanding flight tasks under instrument meteorological conditions: complicated departure, holding, and approach procedures in one case; and VOR-use intersection problems in the other. The other two experiments involved ILS approaches under turbulence, cross wind, and simulated wind shear conditions that imposed heavy control-task loads on the pilots. Significant alcohol effects were found, but only under the heaviest workload conditions. During posttest interviews 75% of the pilots reported physical and/or mental effects due to alcohol.     

Determination of phosphatidyl ethanol (PEth) 16:0/18:1 in dried blood samples of drivers involved in traffic accidents: A pilot study

In routine forensic toxicology practices, blood alcohol concentration (BAC) levels are measured in traffic accidents that ended up in emergency departments. Nevertheless, since the elimination of ethanol from the blood is fast and the detection time is short, BAC cannot indicate the occurrence of chronic excessive alcohol consumption. Phosphatidylethanol (PEth) is a unique ethanol direct biomarker that occurs only in the presence of phospholipase D enzyme in erythrocyte membranes during alcohol intake, and it indicates alcohol intake.In this study, both whole blood and dried blood samples were collected from 50 patients who were admitted to Cukurova University Hospital Emergency Department due to a traffic accident. While studying BAC in whole blood samples, PEth 16:0/18:1 analysis was performed on dried blood samples by LC-MS/MS.According to the BAC (50 mg/dL) value, the legal limit in Turkey, the optimal threshold PEth 16:0/18:1 value was set as 160 ng/mL and over. This study determined that 15 people with above PEth 16:0/18:1 concentrations above 160 ng/mL were classified as excessive alcohol consumption.The data obtained in this study showed a positive correlation between BAC and PEth concentration when driving under the influence of ethanol.     

脾虚证大鼠甘草甜素药物动力学特征及其机制的探讨

 目的探讨脾虚证大鼠甘草甜素(Glycyrrhizin,GL)的药物动力学(Pharmacokinetics,PK)特征及其在胃肠机械运动方面的机制.方法利血平作用于大鼠14 d,制成实验性脾虚证模型,用四君子汤和六味地黄汤反证;用高效液相色谱(HPLC)法测定大鼠体内GL的血药浓度;用高灵敏传感器记录胃和十二指肠运动波.结果与正常对照组比较(1)脾虚模型组血药-时曲线下面积(AUC),血药最高峰浓度(Cmax);半吸收期(T1/2ka)消除速度常数(β)均减小,转运速度常数(K12)增大(P＜0.01);(2)脾虚模型组胃、十二指肠运动功能均减弱(P＜0.01);(3)经四君子汤预防性治疗的大鼠胃肠运动和GL的PK参数与正常对照组比较差异无显著性意义(P＞0.05),但经六味地黄汤治疗组的大鼠各值与正常对照组比较差异有较显著性意义(P＜0.05).结论脾虚大鼠对经口服GL后的吸收、分布、转运和消除均存在异常;血药浓度和生物利用度降低,GL的有效吸收低;胃肠运动功能减弱,可能是脾虚GL的有效吸收降低的机制之一.     

A regression model applied to gender-specific ethanol elimination rates from blood and breath measurements in non-alcoholics

As elimination rates for alcohol are suggested to be gender specific, a novel regression model has been applied to estimate these rates for both men and women using experimentally measured data from 81 female and 96 male volunteers described in previous papers. Breath alcohol measurements were done with the Alcotest 7110 Evidential device and were coupled with concomitant sampling of venous blood. Statistical analyses involved use of a mixed linear model for blood alcohol concentration (BAC) and breath alcohol concentration (BrAC), respectively. The model takes regression lines for each test subject into account with an individual starting value (2 h after the end of drinking) and with an individual alcohol elimination rate per hour (coincidental effects). Further, the data was modeled so that an average alcohol elimination rate per hour could be estimated separately for both genders (constant effects). This enables us to methodically correctly estimate the back calculation. The elimination rates β ₆₀, which can be used for minimum and maximum back calculations for the BAC, were 0.115 g/kg/h and 0.260 g/kg/h, respectively, for women and 0.096 g/kg/h and 0.241 g/kg/h, respectively, for men. These figures widely deviate from gender-unspecific values commonly used in Germany (0.1 and 0.2 g/kg/h, respectively). The corresponding values for the BrAC were 0.061 mg/l/h and 0.124 mg/l/h for women and 0.049 mg/l/h and 0.112 mg/l/h for men. The probability of an over- or underestimation of the abovementioned extreme values is 0.3% in each case.     

Blood alcohol levels in suicide by hanging cases in the state of Sao Paulo, Brazil

Suicide is one of the main causes of violent death worldwide, and has become a public health issue. Since alcohol consumption is associated with the increase in the number of suicides and hanging is one of the main methods used worldwide, the present study consists of an epidemiological analysis of BACs in victims of suicide by hanging autopsied in the State of Sao Paulo, Brazil. The objective of the present work was to establish an epidemiological profile and evaluate blood alcohol concentrations in victims of suicide by hanging in the State of São Paulo, Brazil, in the year of 2007. A cross-sectional retrospective study was conducted by collection of secondary data from autopsy reports of victims of hanging. According to the present study, positive results for alcohol were higher in male victims, but the mean BAC was higher in women.     

Reliability of clinical decisions regarding alcohol influence

In Jordan, pursuing legal procedures related to alcohol intake usually depends on the physicians' clinical judgment. A study was carried out on 825 medico-legal cases over a 2 year period to evaluate the extent of physicians' clinical decisions on patients suspected to be under the influence of alcohol. A significant number of cases (12.6%, n = 104) were found to be positive for alcohol. The study showed that the clinical examination failed to diagnose a large number of cases (78.9%, n = 82). Also, the majority of diagnosed cases (50%, n = 11) had a blood alcohol concentration (BAC) range of 50-100 mg/dl. 32% (n = 33) of the cases with positive BAC were admitted to hospital. A high admission rate was observed when BAC was <50 mg/dl and >150 mg/dl, which constituted 39.3% (n = 13) and 48.5% (n = 16) of the admitted cases respectively. A large number of the admitted cases had either simple or no trauma (48.4%, n = 16) as compared with the control group of cases (21.8%, n = 10). The admission rate of positive BAC cases in traffic accidents was double that of control group. These findings may reflect the unreliability of the clinical decision in positive BAC. Implementing a certain BAC level locally for both clinical and a jurisdiction purposes is strongly recommended.     

肺泡癌的CT诊断（附10例分析）

目的探讨肺泡癌（BAC）的CT表现，评价肺泡癌的CT诊断价值。方法回顾性分析10例肺泡癌的CT表现及其病理基础。结果10例肺泡癌中，斑片状模糊影3例，斑片影伴结书影4例，单发结节影3例。结论肺泡癌的CT表现较特异，CT检查是其诊断和鉴别诊断的理想方法。     

Effects of alcohol on body-sway patterns in human subjects

The vestibulospinal aspects of vestibular function are commonly neglected in the evaluation of alcohol-induced intoxication. Thus, in the present study the effect of an acute intoxication with a low or moderate quantity of alcohol was examined with respect to the equilibrium in 30 healthy subjects. The blood alcohol concentration (BAC) was measured 30 min after the ingestion of the last alcohol, ranging between 0.22 and l.59‰. Stability of stance was quantified by static platform posturography in Romberg-test conditions with eyes open and eyes closed. Among other parameters, the average body sway path (SP) and area of body sway (SA) were assessed. Posturography revealed a significant increase in body sway. There was a positive correlation between SA (or SP) and BAC both with eyes open and eyes closed. Multiple group comparisons revealed that the large-alcohol-dose group (BAC ≥ 1.0‰) could be clearly differentiated from test cases with BAC lower than 0.8‰. Sway area was the most sensitive parameter for detecting increased body sway after alcohol ingestion. The area increase, present not only with eyes closed but with eyes open, revealed an inadequate compensation of the ethanol-induced ataxia by visual stabilization. The Romberg’s quotient, which denotes eyes closed relative to eyes open, remained constant. The increase in sway path with eyes closed showed an omnidirectional sway. A comparison of the sway pattern of subjects after acute ethanol ingestion with the data of patients with permanent cerebellar lesions suggested that the acute effect of alcohol resembles that of a lesion of the spinocerebellum. This finding contrasts with earlier studies, which postulated an acute effect of ethanol resembling that in patients with an atrophy of the anterior lobe of the cerebellum due to chronic alcohol abuse. In seven cases of the lower dose group (BAC ≤ 0.8‰), a reduction in body sway after alcohol ingestion was observed. This finding may be consistent with a dose-related biphasic action of alcohol, which – besides its well-known depressant effects with high doses – also shows stimulatory action with small doses. Received: 5 January 1998 / Received in revised form: 3 July 1998     

Blood alcohol concentration of suicide victims by partial hanging

During the investigated period, 2000–2007, 4249 suicides were reported in Slovenia, and 1061 autopsies of suicide deaths from the central, northwestern, and southwestern parts of Slovenia were conducted at the Institute of Forensic Medicine in Ljubljana. To identify a possible role of alcohol use in the selection of suicide method blood samples were collected during medicolegal autopsies of suicide victims in order to establish their blood alcohol concentration (BAC) level at the time of death. The study group consisted of 844 suicide victims that used violent suicide methods and 174 suicide victims that used non-violent suicide methods. Out of the group with violent suicide methods 184 (21.8%) suicide victims by partial hanging and 112 (13.3%) suicide victims by complete hanging were identified. The average age was higher in the group of suicide victims by partial hanging than in the group of suicide victims by complete hanging (p < 0.001; T = 3653; df = 294). The mean BAC was higher (T = 1.604; df = 278; p < 0.05) in the group of suicide victims by partial hanging (0.57 g/kg; SD ± 0.92) than in the group of suicide victims by complete hanging (0.40 g/kg; SD ± 0.82). The proportion of BAC positive suicide victims with blood alcohol concentration above 0.1 g/kg at the time of death was higher in the group of suicide victims who used non-violent suicide methods in comparison to the group of suicide victims who used violent suicide methods (p < 0.001; χ² = 14.988, df = 1). Partial hanging was almost twice as common as complete hanging. Higher BAC in the group of suicide victims by partial hanging and more BAC positive suicide victims in the group who died by non-violent suicide methods could give indications about the role of alcohol in the selection of suicide method.     

Radiolucencies and cavitation in bronchioloalveolar carcinoma: CT-pathologic correlation

Bronchioloalveolar carcinoma (BAC) is a polymorphic lung cancer the incidence of which is rising. The presence of intratumoral radiolucencies is an important feature of bronchioloalveolar carcinoma.The aim of this study was to present pictorially the spectrum of intratumoral radiolucencies visible in BAC. In 57 BACs studied with thin-slice CT, we identified six types of radiolucencies: (a) patent intratumoral bronchioles (air bronchiologram); (b) pseudocavitations; (c) cavitation; (d) serpentine radiolucencies; (e) internal alveologram; and (f) multiple cystic lesions. Received: 31 December 1997; Revision received: 23 March 1998; Accepted: 28 April 1998     

细支气管肺泡癌的CT与病理对照研究

探讨细支气管肺泡癌的ＣＴ表现的病理基础。材料与方法：对７３例ＢＡＣ进行回顾分析。所有病例均经手术或活检得到组织病学证实。记录病灶边缘及内部特点,与病理切片对照。结论认识ＢＡＣ的Ｃ表现和病理基础,有助于提高诊断水平。     

The effect of blood in the oral cavity on breath alcohol analysis

The theory that blood (containing alcohol) present in the oral cavity may falsely increase breath analysis recently led to a successful appeal against a drink driving conviction. Subjects who had previously consumed vodka (37.2% alc/vol), at 30 ml/10 kg and reached a BAC (blood alcohol concentration) of between 0.05 and 0.10% were then given four oral solutions consisting of a control (distilled water), and 0.05, 0.10 and 0.15% aqueous alcohol (ethanol) solutions, administered in coded form. A four-way cross-over, blind, randomized assay was conducted with the solutions, with breath analyses conducted in the presence or absence of solution in the mouth. The first trial group (n = 18) received 2 ml of solution, and we found that the simulated 0.15, 0.10 and 0.05% alcohol solutions in the mouth produced BAC reading increases of 0.0088 +/- 0.0014, 0.0062 +/- 0.0008 and 0.0055 +/- 0.0010% respectively (p < 0.001). The second trial group (n = 20) received 1 ml of solution and produced BAC reading increases of 0.0047 +/- 0.0011 (p < 0.001), 0.0023 +/- 0.0008 (p < 0.01) and 0.0020 +/- 0.0006% (p < 0.05) respectively. In conclusion, these studies indicate that small volumes of blood (containing alcohol) in the mouth would not have a practical effect on breath analysis readings.     

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.