Individual differences in the kinetics of alcohol absorption and elimination

The individual differences in alcohol pharmacokinetics were studied using the one-compartment model with first-order absorption and zero-order elimination kinetics in humans. The blood alcohol concentrations (BACs) were simulated by obtained parameters, absorption rate constant (ka), and climination rate constant (β). The 81 healthy young Japanese volunteers, who had been divided into those without alcohol-induced facial flushing (nonflushers) and those with facial flushing (flushers) according to alcohol patch test results and a questionnaire beforehand, ingested 0.50 g/kg ethanol within 1 minute. Breath alcohol concentrations (BrACs) were measured during absorption and during the elimination period. BACs were obtained based on BrACs. Fifteen percent of subjects exhibited low BAC profile (below 0.4 mg/mL) (first-pass effect [FPE] group), although the majority showed normal BAC profile (normal group). The ka was approximately 5 to 8 (h⁻¹) in the normal group without significant difference between nonflushers and flushers, whereas that in the FPE group was significantly smaller than in the normal group. For the normal group, peak BACs were well simulated by the one-compartment model with first-order absorption and zero-order elimination kinetics. A considerable portion of subjects exhibited FPE. Absorption of alcohol from the intestine plays an important role in alcohol pharmacokinetics in humans.     

Course of exogenous ethanol in the first hours after death – two experimental approaches

Post-mortem redistribution may contribute to changes in blood alcohol concentration, rendering questionable results in a court of law. Two experimental approaches using Wistar rats and human plasma were developed to improve the reliability of femoral blood in post-mortem alcohol analyses. First, rats were administrated with ethanol (0.6 g/kg, p.o) and 30 min later were euthanized by exposure to CO₂. After perimortem cardiac blood sampling, samples of blood, liver and lung were collected 6, 12 and 24 h post-mortem in order to measure alcohol concentration, water content and haematocrit. Plasma from human corpses obtained from central and peripheral blood was supplemented with ethanol and afterwards incubated at 37?°C. The animal model revealed a significant decrease of both blood alcohol concentration and water content. Moreover, significant differences between central and peripheral sites were observed in human blood autolysis markers, revealing an exacerbation of haemolysis, which in turn affected alcohol stability by the oxidation of alcohol to acetaldehyde. Our study confirmed that both dehydration and autolysis of blood exacerbate alcohol diminution in the central blood in the first six hours after death. This study reinforces the suitability of femoral blood over central blood for ethanol analyses.     

Patient-specific radiation dosimetry for radionuclide therapy of liver tumors with intrahepatic artery rhenium-188 lipiodol

A clinically practical algorithm has been developed for the treatment of liver cancer by the administration of rhenium-188 ((188)Re)-labeled lipiodol via the hepatic artery. This algorithm is based on the "maximum tolerated-activity" paradigm for radionuclide therapy. A small "scout" activity of (188)Re-labeled lipiodol is administered to the patient before the actual therapeutic administration. At approximately 3 hours after administration, the activities in the normal liver, liver tumors, lungs, and total body are measured by gamma camera imaging using the conjugate-view method, with first-order corrections for attenuation (using a (188)Re transmission scan) and scatter (using the "dual-window" method). At the same time, peripheral blood samples are counted, and the activity concentrations in whole blood are calculated. The blood activity concentrations are then converted to red marrow activity concentrations and then total red marrow activity using anatomic data from Standard Man anthropomorphic models. Next, the cumulated activities in the normal liver, liver tumors, lungs, red marrow, and total body are calculated using the measured activities in the respective source regions and conservatively assuming elimination of activity only by physical decay in situ. The absorbed doses to the therapy-limiting normal tissues, liver, lung, and red marrow, are then calculated using the Medical Internal Radiation Dose Committee schema, adjusting the pertinent S factors for differences in total body and organ masses between the patient and the anthropomorphic model and including the dose contribution from the liver tumors. Finally, based on maximum tolerated absorbed doses of 3,000, 1,200, and 150 rad (cGy) to liver, lung, and red marrow, the respective absorbed doses per unit administered activity are used to calculate the therapy activity. Although not required for treatment planning, tumor absorbed dose may also be estimated. This algorithm has been automated using an Excel (Microsoft, Redmond, WA) spreadsheet.     

Comparative analysis of hospital and forensic laboratory ethanol concentrations: A 15 month investigation of antemortem specimens

Quantitative serum alcohol concentrations from regional hospitals (from specimens collected at time of hospital admission) were compared to results from whole blood (from specimens collected at the time of hospital admission) concentrations measured at the San Diego County Medical Examiner's Office (SDCMEO). Over a 15 month period (January 2012 to March 2013), the postmortem forensic toxicology laboratory analyzed a total of 2,321 cases. Of these, 280 were hospital cases (antemortem) representing 12% of the overall Medical Examiner toxicology casework. 59 of the 280 hospital cases (or 21%) screened positive for alcohol (ethanol). 39 of these 59 cases were included in the study based on available specimens for quantitative analyses. This investigation indicated that serum hospital ethanol concentrations correlated well (R² = 0.942) with ethanol values determined at SDCMEO (generally measured in whole blood). There was an observed negative bias with an average of −14.1%. A paired t-test was applied to the data and it was shown that this observed bias is statistically significant. These differences in ethanol concentrations could result from differences in specimen, analytical techniques, and/or calibration. The potential for specimen contamination is also discussed.     

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.     

Interpretation of a highly positive ethyl glucuronide result together with negative fatty acid ethyl esters result in hair and negative blood results

Considering the widespread nature of alcohol-related problems, the diagnosis of excessive alcohol consumption is an important task from medical and legal viewpoints. Alcohol abuse can be documented by usual blood [e.g., carbohydrate deficient transferrin (CDT)] and liver function [e.g., γ-GT or mean corpuscular volume (MCV)] tests, and, over a long-term basis, by hair analysis. Major markers of ethanol consumption in hair are ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs). Detection of EtG in hair is said to be associated with excessive alcohol consumption, whereas a negative result does not unambiguously exclude alcohol abuse. Investigations on FAEEs can also be used to monitor excessive alcohol consumption. Four FAEEs (ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate) are the most suitable markers for the detection of heavy alcohol consumption and show different concentrations in hair of children, adult teetotalers, and social drinkers in comparison with FAEEs concentrations found in the hair of alcoholics. The Society of Hair Testing has provided guidelines for hair testing for chronic excessive alcohol consumption, and states positive cutoffs for a 0–3 cm hair segment as 30 pg/mg and 0.5 ng/mg for EtG and FAEEs, respectively. This study reviews the difficulties in interpreting blood and hair results of a 41-year-old woman involved in a child custody legal dispute. Her EtG and FAEEs concentrations in a 0–3 cm segment were 203 pg/mg and 0.29 ng/mg, respectively, and blood parameters were in the normal range (0.6 %, 93 fl, 14 IU/l for CDT, MCV, and γ-GT, respectively). Although the high EtG concentration suggested excessive drinking behavior, the second hair marker, FAEEs, and the three bloods tests were inconspicuous and in accordance with the claim of abstinence from alcohol by the subject. The woman declared having dyed her hair more than 6 months prior to sampling, use of weight-loss medication, and consumption of about four energy drinks per day. A hair lotion based on ethanolic plant extracts was regularly used by the subject, and could have been a source of contamination. Therefore, we recommend that possible external sources of hair contamination always be taken into consideration, especially if contradictory biological results are obtained and if the subject denies any alcohol intake.     

A study of blood and urine alcohol concentrations in cases of alleged drug-facilitated sexual assault in the United Kingdom over a 3-year period

This paper details the alcohol concentrations found in a selection of 1,014 cases of claimed drug-facilitated sexual assault analysed at The Forensic Science Service, London Laboratory between January 2000 and December 2002. Where appropriate, either a whole blood sample and/or a urine sample was analysed for alcohol, common drugs of abuse and potentially stupefying drugs. The samples were collected from a complainant within 12 h of an alleged incident in 391 of the 1014 cases analysed. Of these, the majority (81%) contained alcohol. The presence of alcohol itself was not surprising as most of the alleged incidents were associated with social situations such as at a public house, bar, night-club or party, where it is expected that alcohol would have been consumed. However, 233 (60%) of the 391 cases had a high back-calculated figure, where high is defined as greater than 150 milligrams per 100 millilitres (150 mg%). Some of these samples were also found to contain illicit drugs. This is the first paper to our knowledge which discusses in detail the significance of the alcohol concentrations found in cases of this type.     

Endogenous ethanol 'auto-brewery syndrome' as a drunk-driving defence challenge

The concentration of ethanol in blood, breath or urine constitutes important evidence for prosecuting drunk drivers. For various reasons, the reliability of the results of forensic alcohol analysis are often challenged by the defence. One such argument for acquittal concerns the notion that alcohol could be produced naturally in the body, hence the term 'auto-brewery' syndrome. Although yeasts such as Candida albicans readily produce ethanol in-vitro, whether this happens to any measurable extent in healthy ambulatory subjects is an open question. Over the years, many determinations of endogenous ethanol have been made, and in a few rare instances (Japanese subjects with very serious yeast infections) an abnormally high ethanol concentration (> 80 mg/dl) has been reported. In these atypical individuals, endogenous ethanol appeared to have been produced after they had eaten carbohydrate-rich foods. A particular genetic polymorphism resulting in reduced activity of enzymes involved in hepatic metabolism of ethanol and a negligible first-pass metabolism might explain ethnic differences in rates of endogenous ethanol production and clearance. Other reports of finding abnormally high concentrations of ethanol in body fluids from ostensibly healthy subjects suffer from deficiencies in study design and lack suitable control experiments or used non-specific analytical methods. With reliable gas chromatographic methods of analysis, the concentrations of endogenous ethanol in peripheral venous blood of healthy individuals, as well as those suffering from various metabolic disorders (diabetes, hepatitis, cirrhosis) ranged from 0-0.08 mg/dl. These concentrations are far too low to have any forensic or medical significance. The notion that a motorist's state of intoxication was caused by endogenously produced ethanol lacks merit.     

Effect of fatigue and alcohol on observer perception.

A test series of chest radiographs containing pseudonodules was used to establish baseline sensitivity, specificity, and accuracy rates for individual observers. This experiment studies the effect of fatigue (as subjectively measured) and alcohol (as measured by blood alcohol levels) on observer perception and performance. The results indicate that the fatigue encountered in the course of ordinary professional activities has no significant effect on diagnostic accuracy. Modest quantities of alcohol may adversely influence diagnostic sensitivity, but the effect is unpredictable. Subjective estimates of the influence of fatigue or alcohol on performance by individual observers are frequently erroneous.     

Evaluation of the contribution of smoking to total blood polonium-210 in Saudi population.

A preliminary study of 210Po concentrations in the blood of some smokers and nonsmokers is presented in order to evaluate the contribution of smoking to total blood 210Po in Saudi population. Blood samples were collected from 30 volunteers and analyzed by high resolution alpha-spectrometry using a radiochemical technique. The technique is based on the separation of polonium from other components of the sample by wet ashing with an HNO3/H2O2 oxidizing mixture and spontaneous deposition on a silver disc under the relevant conditions for alpha-particle counting. The results indicated that a significant fraction (about 30%) of blood 210Po is related to smoking.     

Evaluating alleged drinking after driving--the hip-flask defence. Part 1. Double blood samples and urine-to-blood alcohol relationship

This two-part article examines the strengths and weaknesses of various ways of investigating claims of drinking alcohol after driving, commonly known as the hip-flask or glove-compartment defence. In many countries the onus of proof in hip-flask cases rests on the prosecution. With good co-operation from the police and timely sampling of body fluids, such as blood and urine for forensic analysis of ethanol, useful evidence can be mustered to support or challenge the truthfulness of alleged drinking after driving. The person's blood-alcohol concentration (BAC) can be compared with values expected on the basis of the amount of alcohol consumed after driving, according to theoretical Widmark calculations. The actual BAC measured is then adjusted for the additional amount of alcohol consumed in the after-drink. Double blood samples, that is, taking two specimens of venous blood about 30-60 minutes apart and looking at the magnitude and direction of change in BAC provides little or no more information than a single blood specimen. However, the relationship between alcohol in blood and urine is very useful in hip-flask cases whereby the concentration expected in the primary urine is compared with the concentration in the bladder urine voided. The concentration of alcohol determined in a second urine sample collected 30-60 min later gives supporting evidence in hip-flask cases. A graphical method, which entails plotting ethanol concentrations in blood and urine as a function of time provides a robust and practical way to investigate hip-flask defences. In the second part of the review, congener analysis is presented, which entails comparing the concentrations of n-propanol, isobutanol and occasionally other congeners in the alcoholic beverage allegedly consumed after driving with the volatiles present in the suspect's blood and urine determined by headspace gas chromatography.     

"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.     

The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. I. Toluene, 1,1,1-trichloroethane and butane.

Experimental work has been undertaken to investigate the potential interference of toluene, 1,1,1-trichloroethane and butane with the evidential breath alcohol testing instruments used in Great Britain (Lion Intoximeter 3000 and Camic Breath Analyser). Volunteers inhaled the volatile substances in an exposure chamber for up to 4 hours, at concentrations of 100, 350 and 600ppm respectively. Subsequently breath was tested on leaving the chamber. No interference was observed with the breath alcohol instruments when the subjects were exposed to toluene and 1,1,1-trichloroethane. A short-term response immediately after exposure was observed for subjects exposed to butane. Further analytical work involving blood and breath samples demonstrated that all three volatile substances were absorbed during exposure and were detectable in blood for at least 3 hours post-exposure. Their elimination post-exposure followed an exponential decay.     

Alkoholbedingte Fahruntüchtigkeit

The judgement and evidence on offences related to alcohol impaired driving by expert witnesses essentially relates to the following areas: the analysis of blood and breath alcohol, back calculation of blood alcohol concentrations (BAC) to the time of the offence, absconding after an accident, and calculation and judgement of post-offence drinking, including congener analysis, calculation of BAC from consumption statements, judgment of relative driving inability and responsibility in case opinion on functional and metabolic alcohol tolerance, alcohol abuse and medical psychological investigation. Relevant basics of alcohol physiology (“ethanology”) and of widely accepted forensic standards are presented.     

Alcohol congener analysis and the source of alcohol: a review

For many decades traditional alcohol congener analysis has provided the concentrations of fermentation by-product congeners found in blood, to ascertain if the claims of an individual regarding the alcoholic beverage(s) they have consumed were feasible, assisting in cases where after-drinking is involved. However, this technique does not provide information on the exact alcoholic beverage(s) consumed. More recently, ingredient biomarker congeners specific to certain alcoholic beverages have been detected in blood, making it possible to identify the particular alcoholic beverage consumed and therefore the source of alcohol (albeit only for a limited number of beverages). This novel approach may reduce current limitations that exist with traditional methods of detecting fermentation by-product congeners, which restrict the use of alcohol congener analysis internationally and for other medico-legal scenarios. This review examines the forensic application of alcohol congener analysis in determining the source of alcohol and other techniques.     

Effect of alcohol and marijuana on eye movements.

The effects of alcohol and marijuana (tetrahydrocannabinol-THC) on saccades, smooth pursuit, and optokinetic nystagmus were quantitatively evaluated in 24 normal subjects using electro-oculographic recordings. Each subject was given an initial trial run and then tested three times (at weekly intervals) with either 0.0microgram THC or 100 microgram THC/kg bodyweight while at three different blood alcohol concentrations (0.0, 0.05 and 0.1%). A 2X3 factorial design was used. Saccades and smooth pursuit were induced by a dot of light moving in steps and ramps on a modified television set. Optokinetic nystagmus was induced by a cloth drum completely surrounding the subject and moving at a constant velocity of 30 degrees/s. Alcohol (0.05 and 0.1%) alone produced significant (p less than 0.05) impairment of saccade maximum velocity and reaction time, smooth pursuit velocity, and optokinetic slow-component velocity. The addition of THC caused performance to further deteriorate at each blood alcohol level but, in all but one instance, the added effect was not statistically significant ( greater than 0.05). At the THC and alcohol concentrations used in this study, the eye movement effects of alcohol over-shadowed those of marijuana.     

A pixel-based autofocusing technique for digital histologic and cytologic slides.

The present paper describes a method for autofocusing specifically studied for the acquisition of digital slides, i.e. full histologic and cytologic slides, utilising low-cost equipment. At first, experimentations with some of the most used focus measures and algorithms have been made, in order to choose the most suitable for histologic and cytologic images. Then, a study of the specific features of digital slides has been preliminarily carried out in order to understand the constraints of the domain. These included the capability of autofocusing in an unattended way on thousands of microscope fields, while fast performance is not a strict requirement. Based on the findings, an algorithm based on a dynamic focus position space, with a variance-based focus measure has been adapted to the specific situation. A qualitative and quantitative evaluation of the proposed algorithm allowed us to show that the proposed algorithm is suitable for the acquisition of digital slides, and furthermore it can be implemented starting from a basic microscope with an inexpensive motorised stage. The algorithm is currently implemented into a complete digital slide acquisition system, which is in turn being used for a Quality Assurance Programme in cervicovaginal cytologic screening.     

Zur Zuverlässigkeit der Blutalkoholbestimmung. Das Verteilungsverhältnis des Wassers zwischen Serum und Vollblut

In the guidelines for determination of the blood alcohol level for forensic purposes, a correction factor of 1.2 has been established for the conversion of serum alcohol into blood alcohol based on the relationship of the water content between serum and whole blood. The reliability of the determination of the blood alcohol level is dependent on the possible minimum and maximum values of this correction factor. In a comprehensive multicenter study consisting of 833 samples, which can be considered representative of persons involved in offences under the drinking and driving act, an average quotient of 1.16 was found with minimum and maximum values of 1.08 and 1.21 respectively. In 96% of the cases the quotient was between 1.13 and 1.19 and the deviation of the quotient from the average value was less than 3%. From these results it can be assumed that the determination of blood alcohol is obviously more reliable than previously presumed.     

Iterative blind deconvolution in magnetic resonance brain perfusion imaging.

In first pass magnetic resonance brain perfusion imaging, arterial input functions are used in the deconvolution of the observed contrast concentrations to obtain quantitative hemodynamic parameters. Ideally, arterial input functions should be measured in each imaged voxel to eliminate the effects of delay and dispersion of the contrast agent from the injection site. An approach based on iterative blind deconvolution with the Richardson-Lucy algorithm is proposed for the simultaneous estimation of voxel-specific arterial input functions and voxel-specific tissue residue functions. An extended contrast concentration model was used to separate the first pass bolus from additional recirculation and leakage signals. The extended model was evaluated using in vivo data. Computer simulations examined the feasibility of iterative blind deconvolution in perfusion imaging. Preliminary in vivo results from a patient with fibromuscular dysplasia showed territories with delayed/dispersed arterial input functions that coincided with the location of territories supplied by collateral circulation as described from the complete radiologic examination. Higher flow values and shorter mean transit times compared to conventional methods were obtained in these areas, suggesting that the effects of dispersion were minimized. The in vivo estimated arterial input functions visualized the patient's blood supply patterns as a function of time.