Blood alcohol levels in Finnish victims of non-ischaemic sudden cardiac death.

INTRODUCTION: Non-ischaemic heart disease (NIHD) is the underlying pathology in∼20% of all sudden cardiac deaths (SCDs). Heavy drinking is known to be associated with SCD due to ischaemic heart disease, but studies on association of recent alcohol consumption and SCD in patients with NIHD are scarce. We evaluated the blood alcohol levels of autopsy verified non-ischaemic SCD victims. METHODS: Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) (n = 5869, mean age 65 ± 12, 79% males). All deaths occurred in Northern Finland during 1998-2017. All victims underwent a medico-legal autopsy. Subjects of SCD due to ischaemic heart disease were excluded. RESULTS: A total of 1301 (mean age 57 ± 12, 78% males) victims of SCD due to NIHD were included in the study. The blood ethanol level was elevated in 543 (42%) subjects, out of which the blood alcohol level was ≥0.10%in 339 (62%) subjects and ≥0.15%in 252 (46%) subjects. Male SCD victims had alcohol in blood more frequently compared to females (45% versus 31%, p < .001). CONCLUSION: Elevated blood alcohol level is common in SCD victims due to NIHD, especially in males. Recent alcohol consumption might contribute to the subsequent SCD in many non-ischaemic SCD victims.KEY MESSAGESElevated blood alcohol level is common in victims of sudden cardiac death due to non-ischaemic heart disease, especially in males.Recent alcohol consumption may contribute to the subsequent death in many nonischemic sudden cardiac death victims.

Quirks of dye nomenclature. 13. Biebrich scarlet.

Biebrich scarlet was the first commercial bis-azo dye when it appeared on the market in 1879 in Biebrich on Rhine, Germany. The dye's early history is recounted here with details of the manufacturing process. The possibility that the dye exists in a keto form rather than an enol form is discussed. Application as a textile dye was soon followed by use as a biological stain and for medical applications. Efforts to decolorize the dye to reduce environmental impact are described.

Reference values for osmolal gap in healthy subjects and in medical inpatients.

Methanol and ethylene glycol poisonings are associated with high morbidity and mortality rates if treatment is not initiated early. Since few hospitals measure these toxic alcohols on a 24/7 basis, calculation of the osmolal gap (OG) is an important diagnostic tool. The reference value for the OG lacks consensus. We, therefore, wanted to update the reference value for OG in presumed healthy subjects and study OG values in internal medicine patients. The OG was calculated in 285 patients at the Medical Clinic at Oslo University Hospital, and in 118 healthy blood donors at Vestfold Hospital Trust. OG was calculated by the formula: OG = Measured osmolality - calculated osmolality ((1.86 × s-sodium + s-glucose + s-urea)/0.93) mOsm/kg H2O. In the patients, median OG was 0 mOsm/kg H2O (interquartile range -3 to 3 mOsm/kg H2O, range -16 to103 mOsm/kg H2O). When corrected for one outlier, the central 95% interval for OG was -10 to 20. The healthy blood donors had a median OG of -1 mOsm/kg H2O (interquartile range -3 to1 mOsm/kg H2O, range -13 to 8 mOsm/kg H2O). When corrected for outliers, the reference range was -6 to 5 mOsm/kg H2O. Based on results from a healthy population, we suggest a reference value for the OG of ≤5 mOsm/kg H2O, but also recommend, based on our results from medical inpatients, to keep today's practice for suspecting poisoning with toxic alcohols at an elevated OG of ≥20 mOsm/kg H2O.

Dynamic headspace analysis using online measurements: Modeling of average and initial concentration.

Dynamic headspace sampling is an important technique for the analysis of consumer products, the study of biological samples and environmental water analyses. This paper shows the influence of experimental conditions, such as the sampling time, sampling flow rate, headspace volume, liquid volume and Henry coefficient on the measured average concentration values. A corresponding closed expression as function of these variables is introduced in order to quantify the deviation of the initial headspace concentration. The proposed bi-exponential function embeds different current existing models for recovery calculation in dynamic sampling analyses in one single expression. A fully automated and user-friendly Excel® file to investigate or to model the dynamic headspace sampling results is added to everyone's easy use.

QSAR modeling of adipose/blood partition coefficients of Alcohols, PCBs, PBDEs, PCDDs and PAHs: A data gap filling approach.

Physiologically-based toxicokinetic (PBTK) model has immense role to play in the risk assessment process due to specified mathematical representation of the absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) of chemicals in diverse environmental compartment. Determination of adipose/blood partition coefficient [logP(adipose/blood)] is regarded as one of the crucial constraints of PBTK models. In respect to the challenge for identifying the chemical-definite parameters for these models, especially within short time frame and with limited resources, quantitative structure-activity relationship (QSAR) models are beneficial for providing the chemical-specific parameters of PBTK models. In the present study, we have developed robust, statistically highly significant (R2 = 0.92, QLOO2 = 0.90, RPred2 = 0.92) and mechanistically interpretable three descriptors QSAR models for 67 environmental chemicals [Alcohols, polybrominated diphenyl ethers (PBDEs), polychlorinated dibenzodioxins (PCDDs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs)] employing the experimental values of adipose/blood partition coefficient for human. The partitioning of chemicals into adipose tissue and blood offers information related to distribution and toxicological effects of these molecules in to the mammal system. The developed models are helpful to understand the mechanistic basis of toxicokinetic processes into the mammal system followed by risk assessment and risk management process. The applicability domain (AD) of the developed model was checked and followed by its employment to predict adipose/blood partition coefficient of 513 environmental contaminants consist of PCBs, PBDEs, PCDDs and PAHs from USA Environmental protection agency (US EPA) site.

Cost-effective smartphone-based reconfigurable electrochemical instrument for alcohol determination in whole blood samples.

The determination of ethanol intoxication in whole blood samples may open the opportunity for a precise and quick point-of-measurement in the ambit of medical emergency or law enforcement. In contrast with traditional techniques based on breath sampling, direct blood measurements present greater immunity to errors specially in case of unconscious or non-collaborative patients. In this context, a portable, sensitive and easy-to-use instrument is highly desirable. In the current work we present a smartphone-based µPotentiostat which combines a novel circuital technique for sensor readout digitalization with a reusable lab-on-a-chip (LoC) concept. Such system allows both chronoamperometric and cyclic voltammetry measurements with a reduced number of electronic components on a very compact PCB (38.5â€¯× 22.5 mm2). Power, data-link and user interface are provided in combination with a standard smartphone, enabling cost-effectiveness and reconfigurability without sacrificing precision. The readout platform discussed in this work has been coupled to a LoC for point-of-care combining Pt electrodes microfabricated on silicon substrate for electrochemical measurement and a microfluidic structure of methacrylate for fluid management. Biosensing is enabled by in situ electrodeposition of a calcium alginate hydrogel containing horseradish peroxidase (HPR) and alcohol oxidase (AOx) for selective ethanol detection. Alginate membrane electrodeposition has been here optimized for rapid generation (2 min) and to retain the cellular fraction, thus allowing the measurement in whole blood samples. The µPotentiostat features a sensitivity of 36 nA/g L-1 to ethanol concentration in blood in the 0-1.25 g;L-1 range, with a limit of quantification (LoQ) of 4.5 nA, which is a suitable response for discerning the legal, illegal, severely illegal thresholds in a 40 µL sample of blood.

Impact of day-of-injury alcohol consumption on outcomes after traumatic brain injury: A meta-analysis.

Although a known risk factor for traumatic brain injury (TBI), alcohol has been found to both promote and protect against secondary brain damage. However, it is presently unclear whether the cognitive, psychological and medical/functional outcomes of adults who have consumed alcohol prior to sustaining a TBI differ from those who have not. This meta-analysis examined the outcomes of groups that differed in terms of their day-of-injury (DOI) blood alcohol levels (BALs) by comparing positive with zero BAL (BAL+/BAL-) and high with low BAL (BALhigh/BALlow) samples. The PubMed, PsycINFO, EMBASE, and Scopus databases were searched from inception until the end of March 2015. Hedge's g effects (continuous data) and odds ratios (categorical data) were calculated for 27 studies that compared either the outcomes of BAL+ and BAL- groups or BALhigh and BALlow groups. BAL+ was associated with significantly poorer cognitive outcomes (overall and on general tests) and higher levels of disability, and BALhigh was associated with shorter stays in intensive care. More generally, however, most effect sizes were small to low-moderate in size, non-significant and inconsistent in their direction. Although DOI alcohol consumption increases the risk of sustaining a TBI, it is not consistently associated with better or worse outcomes, other than subtle cognitive deficits; the source of which remains to be determined.

Standardisation and use of the alcohol biomarker carbohydrate-deficient transferrin (CDT).

Carbohydrate-deficient transferrin (CDT) is a glycoform profile of serum transferrin that increases in response to sustained high alcohol intake and over the last decades has become an important alcohol biomarker with clinical and forensic applications. However, the wide range of CDT measurement procedures has resulted in lack of uniform results and reference limits, and hampered comparison of results. In 2005, the IFCC therefore founded a special working group (WG) aiming for standardisation of CDT measurement. This review summarises the history of CDT and the actions taken by the WG-CDT. Initial steps included the definition of the measurand (serum disialotransferrin to total transferrin fraction expressed in %), and the determination of a well-defined anion-exchange HPLC procedure as the candidate reference measurement procedure (cRMP). Subsequent achievements were the establishment of a network of reference laboratories to perform the cRMP, setting a reference interval, and development of a reference material based on human serum for which the laboratory network assign values. Using a set of reference materials for calibration allowed for achieving equivalence of results of all present CDT measurement procedures. The final steps of the WG-CDT have been a full validation of the cRMP to make it an IFCC approved RMP, and providing guidance for international standardisation of all CDT measurement procedures.

Blood alcohol in victims of sudden cardiac death in northern Finland.

AIMS: Momentary intake of large quantity of alcohol provokes ventricular ectopic activity increasing electrical instability. The present study was aimed to assess the prevalence of alcohol intake prior to a sudden cardiac death (SCD) event. METHODS AND RESULTS: Victims of unexpected SCD [n = 2363, age 61 ± 12 years, males 1940 (82%)] included in the Finnish study of genotype and phenotype profiles of SCD (FINGESTURE) had a thorough interview of family members, medico-legal autopsy, and determination of blood alcohol concentration. Because of the Finnish law, all unexpected deaths undergo medico-legal autopsy. Patients who were admitted to a hospital due to an acute myocardial infarction [n = 128, age 63 ± 10 years, males 100 (78%)] served as controls. Based on autopsy findings, 1691 of these victims had ischaemic heart disease (IHD) and were included in the present analysis. A total of 646 (38%) SCD victims with IHD had a blood ethanol concentration above 0‰. Of these victims with blood alcohol test positive, 41% (n = 264) had blood ethanol concentration ≥1.5‰ and 56% (n = 362) ≥1‰. Male SCD victims had more frequently alcohol in blood than the females (40 vs. 27%, P < 0.001, respectively). None of the controls, who gave a consent for the blood ethanol concentration determination (n = 88), had alcohol in blood. Of the controls, 40 (31%) declined to participate in the study and give the consent for blood alcohol testing. CONCLUSION: Almost 4 of 10 of the victims of unexpected SCD have evidence of alcohol intake before the fatal event in the northern Finland autopsy population.

One-step extraction and quantitation of toxic alcohols and ethylene glycol in plasma by capillary gas chromatography (GC) with flame ionization detection (FID).

OBJECTIVES: Clinical analysis of volatile alcohols (i.e. methanol, ethanol, isopropanol, and metabolite acetone) and ethylene glycol (EG) generally employs separate gas chromatography (GC) methods for analysis. Here, a method for combined analysis of volatile alcohols and EG is described. DESIGN AND METHODS: Volatile alcohols and EG were extracted with 2:1 (v:v) acetonitrile containing internal standards (IS) 1,2 butanediol (for EG) and n-propanol (for alcohols). Samples were analyzed on an Agilent 6890 GC FID. The method was evaluated for precision, accuracy, reproducibility, linearity, selectivity and limit of quantitation (LOQ), followed by correlation to existing GC methods using patient samples, Bio-Rad QC, and in-house prepared QC material. RESULTS: Inter-day precision was from 6.5-11.3% CV, and linearity was verified from down to 0.6mmol/L up to 150mmol/L for each analyte. The method showed good recovery (~100%) and the LOQ was calculated to be between 0.25 and 0.44mmol/L. Patient correlation against current GC methods showed good agreement (slopes from 1.03-1.12, and y-intercepts from 0 to 0.85mmol/L; R(2)>0.98; N=35). Carryover was negligible for volatile alcohols in the measuring range, and of the potential interferences tested, only toluene and 1,3 propanediol interfered. The method was able to resolve 2,3 butanediol, diethylene glycol, and propylene glycol in addition to the peaks quantified. CONCLUSIONS: Here we describe a simple procedure for simultaneous analysis of EG and volatile alcohols that comes at low cost and with a simple liquid-liquid extraction requiring no derivitization to obtain adequate sensitivity for clinical specimens.

Influence of tobacco smoke exposure on pharmacokinetics of ethyl alcohol in alcohol preferring and non-preferring rats.

BACKGROUND: A vast majority of people who abuse alcohol are also defined as "heavy smokers". Tobacco smokes induces CYP1A1, CYP1A2, CYP2A6 isoenzymes, but on the other hand, ethanol activates CYP2E1, which can be important during combined, chronic use of both of them. The aim of the study was to evaluate the influence of tobacco smoke xenobiotics on ethanol pharmacokinetics and the level of its metabolites in alcohol preferring and non-preferring rats. METHODS: Ethanol, acetaldehyde, methanol, n-propanol and n-butanol were determined in whole blood by means of gas chromatography. Cotinine in serum was determined by LC-MS/MS. A non-compartmental analysis (cotinine, acetaldehyde) and Widmark equation (ethanol) were used for pharmacokinetic parameters calculation. RESULTS: Ethanol levels were lower in animals exposed to tobacco smoke compared to rats receiving this xenobiotic, without a prior exposure to tobacco smoke. Lower values of the studied pharmacokinetic parameters were observed in the alcohol preferring males compared to the non-alcohol preferring rats. Both n-propanol and n-butanol had higher values of the pharmacokinetic parameters analyzed in the animals exposed to tobacco smoke and ethanol compared to those, which ethanol was administered only once. CONCLUSIONS: An increase in maximum concentration and the area under concentration-time curve for ethanol after its administration to rats preferring alcohol and exposed to tobacco smoke are accompanied by a decrease in the volume of distribution. The changes in the volume of distribution may be caused by an increase in the first-pass effect, in the intestinal tract and/or in the liver. The acetaldehyde elimination rate constant was significantly higher in alcohol-preferring animals.

Development and validation of an LC-MS/MS method for the determination of pelubiprofen and its active metabolite, trans-alcohol, in human plasma and its application to pharmacokinetic study.

A suitable liquid chromatography tandem mass spectrometry (LC-MS/MS) method is required to determine pelubiprofen and its active metabolite, trans-alcohol (M-D), in human plasma for pharmacokinetic studies of pelubiprofen preparations. After one-step liquid-liquid extraction (LLE) using methyl tert-butyl ether (MTBE), pelubiprofen, M-D, and tolbutamide (the internal standard, IS) were eluted from a Capcellpak C18 ACR column using a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile at a flow rate 0.35mL/min. The achieved lower limits of quantitation (LLOQ) of pelubiprofen and M-D were both 15ng/mL (S/N>10) and the standard calibration curves for pelubiprofen and M-D were linear (correlation coefficients >0.99) over the studied concentration range (15-2000ng/mL). Intra- and inter-day precisions were within 7.62% for all analytes and the deviation of assay accuracies was within ±13.23%. The developed method was successfully applied to a pharmacokinetic study of pelubiprofen in healthy Korean male volunteers.

Importance of genetics in fetal alcohol effects: null mutation of the nNOS gene worsens alcohol-induced cerebellar neuronal losses and behavioral deficits.

The cerebellum is a major target of alcohol-induced damage in the developing brain. However, the cerebella of some children are much more seriously affected than others by prenatal alcohol exposure. As a consequence of in utero alcohol exposure, some children have substantial reductions in cerebellar volume and corresponding neurodevelopmental problems, including microencephaly, ataxia, and balance deficits, while other children who were exposed to similar alcohol quantities are spared. One factor that likely plays a key role in determining the impact of alcohol on the fetal cerebellum is genetics. However, no specific gene variant has yet been identified that worsens cerebellar function as a consequence of developmental alcohol exposure. Previous studies have revealed that mice carrying a homozygous mutation of the gene for neuronal nitric oxide synthase (nNOS-/- mice) have more severe acute alcohol-induced neuronal losses from the cerebellum than wild type mice. Therefore, the goals of this study were to determine whether alcohol induces more severe cerebellum-based behavioral deficits in nNOS-/- mice than in wild type mice and to determine whether these worsened behavior deficits are associated with worsened cerebellar neuronal losses. nNOS-/- mice and their wild type controls received alcohol (0.0, 2.2, or 4.4mg/g) daily over postnatal days 4-9. In adulthood, the mice underwent behavioral testing, followed by neuronal quantification. Alcohol caused dose-related deficits in rotarod and balance beam performance in both nNOS-/- and wild type mice. However, the alcohol-induced behavioral deficits were substantially worse in the nNOS-/- mice than in wild type. Likewise, alcohol exposure led to losses of Purkinje cells and cerebellar granule cells in mice of both genotypes, but the cell losses were more severe in the nNOS-/- mice than in wild type. Behavioral performances were correlated with neuronal number in the nNOS-/- mice, but not in wild type. Thus, homozygous mutation of the nNOS gene increases vulnerability to alcohol-induced cerebellar dysfunction and neuronal loss. nNOS is the first gene identified whose mutation worsens alcohol-induced cerebellar behavioral deficits.

High frequency and intensity of drinking may attenuate increased inflammatory cytokine levels of major depression in alcohol-use disorders.

AIMS: As major depression (MD) is often comorbid with alcohol-use disorders (AUD) and alcohol itself modulates the immune system, we examined serum levels of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF), and interferon (IFN)-γ in AUD patients with and without MD. Putative interactions between alcohol variables and MD on cytokine levels were also assessed. METHODS: A consecutive sample of inpatients with AUD (N = 176) from eight alcohol treatment centers in Kathmandu, Nepal, was assessed for alcohol use and depression by administering fully structured psychiatric interviews. Serum cytokine levels were determined using multiplex technology. RESULTS: Alcohol-use disorders patients with a positive history of MD had higher levels of the inflammatory cytokines IL-6 (P = 0.019), TNF (P = 0.020), and IFN-γ (P = 0.001), but not of IL-10 (P = 0.853). AUD patients with MD had higher concentrations of cytokines compared with those without, regardless of the severity of the alcohol problem, but the difference was greater among those drinking in lower frequency and intensity. CONCLUSION: These findings provide evidence for altered functioning of the immune system in AUD patients with comorbid MD. However, frequent and intense drinking may attenuate the difference in the cytokine profiles between AUD patients with and without MD.

microRNA-206 in rat medial prefrontal cortex regulates BDNF expression and alcohol drinking.

Escalation of voluntary alcohol consumption is a hallmark of alcoholism, but its neural substrates remain unknown. In rats, escalation occurs following prolonged exposure to cycles of alcohol intoxication, and is associated with persistent, wide-ranging changes in gene expression within the medial prefrontal cortex (mPFC). Here, we examined whether induction of microRNA (miR) 206 in mPFC contributes to escalated alcohol consumption. Following up on a microarray screen, quantitative real-time reverse transcription PCR (qPCR) confirmed that a history of dependence results in persistent (>3weeks) up-regulation of miR-206 expression in the mPFC, but not in the ventral tegmental area, amygdala, or nucleus accumbens. Viral-mediated overexpression of miR-206 in the mPFC of nondependent rats reproduced the escalation of alcohol self-administration seen following a history of dependence and significantly inhibited BDNF expression. Bioinformatic analysis identified three conserved target sites for miR-206 in the 3'-UTR of the rat BDNF transcript. Accordingly, BDNF was downregulated in post-dependent rats on microarray analysis, and this was confirmed by qPCR. In vitro, BDNF expression was repressed by miR-206 but not miR-9 in a 3'-UTR reporter assay, confirming BDNF as a functional target of miR-206. Mutation analysis showed that repression was dependent on the presence of all three miR-206 target sites in the BDNF 3'-UTR. Inhibition of miR-206 expression in differentiated rat cortical primary neurons significantly increased secreted levels of BDNF. In conclusion, recruitment of miR-206 in the mPFC contributes to escalated alcohol consumption following a history of dependence, with BDNF as a possible mediator of its action.

Chronic sleep restriction disrupts sleep homeostasis and behavioral sensitivity to alcohol by reducing the extracellular accumulation of adenosine.

Sleep impairments are comorbid with a variety of neurological and psychiatric disorders including depression, epilepsy, and alcohol abuse. Despite the prevalence of these disorders, the cellular mechanisms underlying the interaction between sleep disruption and behavior remain poorly understood. In this study, the impact of chronic sleep loss on sleep homeostasis was examined in C57BL/6J mice following 3 d of sleep restriction. The electroencephalographic power of slow-wave activity (SWA; 0.5-4 Hz) in nonrapid eye movement (NREM) sleep and adenosine tone were measured during and after sleep restriction, and following subsequent acute sleep deprivation. During the first day of sleep restriction, SWA and adenosine tone increased, indicating a homeostatic response to sleep loss. On subsequent days, SWA declined, and this was accompanied by a corresponding reduction in adenosine tone caused by a loss of one source of extracellular adenosine. Furthermore, the response to acute sleep deprivation (6 h) was significantly attenuated in sleep-restricted mice. These effects were long-lasting with reduced SWA and adenosine tone persisting for at least 2 weeks. To investigate the behavioral consequences of chronic sleep restriction, sensitivity to the motor-impairing effects of alcohol was also examined. Sleep-restricted mice were significantly less sensitive to alcohol when tested 24 h after sleep restriction, an effect that persisted for 4 weeks. Intracerebroventricular infusion of an adenosine A1 receptor antagonist produced a similar decrease in sensitivity to alcohol. These results suggest that chronic sleep restriction induces a sustained impairment in adenosine-regulated sleep homeostasis and consequentially impacts the response to alcohol.

Determination of three triterpene alcohols in rat plasma after oral administration of pollen of Brassica campestris based on the utilization of fetal bovine serum as surrogate matrix.

24-Dehydropollinstanol (DEH), 24-methylene cholesterol (MET) and 31-norcycloartenol (NOR) are the functional triterpene alcohols of pollen of Brassica campestris. To study the pharmacokinetics of the above components of pollen of B. campestris in rats, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed. To avoid the interference of endogenous MET in rat plasma, fetal bovine serum (FBS) was selected as surrogate matrix and validated. Rat plasma was liquid-liquid extracted, then the chromatographic separation was conducted on a poroshell 120 SB C18 column (2.7µm, 2.1mm×50mm) at 38°C within 5.6min utilizing a gradient elution with a mobile phase consisting of (A) 0.1% formic acid in water and (B) 0.1% formic acid in methanol. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode using positive atmospheric pressure chemical ionization (APCI). The method was validated over the concentration of 9.8-1560ng/ml; the inter-and-intra-day precisions (RSD %) were ≤7.8%, and the accuracies (RE %) were -5.3% to 12.2%, the extraction recovery ranged from 73.5% to 106.9% for all of these analytes, and no obvious matrix effect was observed. The developed method was applied successfully to study the pharmacokinetics of DEH, MET and NOR in rats after oral administration of pollen of B. campestris.

Determination of total and unbound warfarin and warfarin alcohols in human plasma by high performance liquid chromatography with fluorescence detection.

Two analytical procedures are presented for the determination of the total content and unbound fraction of both warfarin and warfarin alcohols in human plasma. Chromatographic separation was carried out in isocratic conditions at 25°C on a C-18 reversed-phase column with a mobile phase consisting of a 70% buffer phosphate 25mM at pH=7, 25% methanol and 5% acetonitrile at a flow rate of 1.2mL/min. Fluorescence detection was performed at 390nm (excitation wavelength 310nm). Neither method showed any detectable interference or matrix effect. Inter-day recovery of the total warfarin and warfarin alcohols at a concentration level of 1000ng/mL was 89±3% and 73±3%, respectively, whereas for their unbound fraction (at a concentration level of 10ng/mL) was 66±8% and 90±7%, respectively. The intra- and inter-day precision (assessed as relative standard deviation) was <10% for both methods. The limits of detection were 0.4 and 0.2ng/mL for warfarin and warfarin alcohols, respectively. The methods were successfully applied to a pooled plasma sample obtained from 69 patients undergoing warfarin therapy.

The 'gap' in the 'plasma osmolar gap'.

Ethylene glycol poisoning is a medical emergency that presents challenges for clinicians and clinical laboratories. If left untreated, it may cause morbidity and death, but effective therapy is available if diagnosed in time. The diagnosis of ethylene glycol poisoning is not always straightforward and the commonly quoted 'plasma osmolar gap' is not sufficiently sensitive to exclude a small ingestion and has been reported to be normal in a number of serious exposures. The 'plasma osmolar gap' cannot distinguish among ethanol, isopropyl alcohol, methanol or ethylene glycol. Thus, the measurement of serum ethylene glycol and, ideally, glycolic acid, its major toxic metabolite in serum, is definitive. This also holds true for methanol and its metabolite formic acid. Ethylene glycol metabolites target the kidney and lead to reversible oliguric or anuric injury, which in turn slows the elimination of ethylene glycol. The therapeutic options include reversal of metabolic acidosis, inhibition of alcohol dehydrogenase and early haemodialysis.

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.