Elevated blood-ethanol concentration promotes reduction of aliphatic ketones (acetone and ethyl methyl ketone) to secondary alcohols along with slower oxidation to aliphatic diols.

Many people convicted for drunken driving suffer from an alcohol use disorder and some traffic offenders consume denatured alcohol for intoxication purposes. Venous blood samples from people arrested for driving under the influence of alcohol were analyzed in triplicate by headspace gas chromatography (HS-GC) using three different stationary phases. The gas chromatograms from this analysis sometimes showed peaks with retention times corresponding to acetone, ethyl methyl ketone (2-butanone), 2-propanol, and 2-butanol in addition to ethanol and the internal standard (1-propanol). Further investigations showed that these drink-driving suspects had consumed an industrial alcohol (T-Red) for intoxication purposes, which contained > 90% w/v ethanol, acetone (~ 2% w/v), 2-butanone (~ 5% w/v) as well as Bitrex to impart a bitter taste. In n = 75 blood samples from drinkers of T-Red, median concentrations of ethanol, acetone, 2-butanone, 2-propanol and 2-butanol were 2050 mg/L (2.05 g/L), 97 mg/L, 48 mg/L, 26 mg/L and 20 mg/L, respectively. In a separate GC analysis, 2,3-butanediol (median concentration 87 mg/L) was identified in blood samples containing 2-butanone. When the redox state of the liver is shifted to a more reduced potential (excess NADH), which occurs during metabolism of ethanol, this favors the reduction of low molecular ketones into secondary alcohols via the alcohol dehydrogenase (ADH) pathway. Routine toxicological analysis of blood samples from apprehended drivers gave the opportunity to study metabolism of acetone and 2-butanone without having to administer these substances to human volunteers.

High dynamic range spatial mode decomposition.

An accurate readout of low-power optical higher-order spatial modes is of increasing importance to the precision metrology community. Mode sensors are used to prevent mode mismatches from degrading quantum and thermal noise mitigation strategies. Direct mode analysis sensors (MODAN) are a promising technology for real-time monitoring of arbitrary higher-order modes. We demonstrate MODAN with photo-diode readout to mitigate the typically low dynamic range of CCDs. We look for asymmetries in the response of our sensor to break degeneracies in the relative alignment of the MODAN and photo-diode and consequently improve the dynamic range of the mode sensor. We provide a tolerance analysis and show methodology that can be applied for sensors beyond first order spatial modes.

Increased sensitivity of higher-order laser beams to mode mismatches.

This Letter derives explicit factors linking mode-mismatch-induced power losses in Hermite-Gauss optical modes to the losses of the fundamental spatial mode. Higher-order modes are found to be more sensitive to beam parameter mismatches. This is particularly relevant for gravitational-wave detectors, where lasers employing higher-order optical modes have been proposed to mitigate thermal noise, and quantum-enhanced detectors are very susceptible to losses. This work should inform mode matching and squeezing requirements for Advanced+ and third generation detectors.

The effects of bovine colostrum supplementation on in vivo immunity following prolonged exercise: a randomised controlled trial.

BACKGROUND: Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction, but there is a lack of research with clinically relevant in vivo measures. AIM: To investigate the effects of COL supplementation on in vivo immunity following prolonged exercise using experimental contact hypersensitivity (CHS) with the novel antigen diphenylcyclopropenone (DPCP). METHODS: In a double-blind design, 31 men were randomly assigned to COL (20 g/day) or placebo (PLA) for 58 days. Participants ran for 2 h at 60% maximal aerobic capacity on day 28 and received a primary DPCP exposure (sensitisation) 20 min after. On day 56, participants received a low-dose-series DPCP challenge to elicit recall of in vivo immune-specific memory (quantified by skinfold thickness 24 and 48 h later). Analysis of the dose-response curves allowed determination of the minimum dose required to elicit a positive response (i.e., sensitivity). RESULTS: There was no difference in summed skinfold thickness responses between COL and PLA at 24 h (p = 0.124) and 48 h (p = 0.405). However, sensitivity of in vivo immune responsiveness was greater with COL at 24 h (p < 0.001) and 48 h (p = 0.023) with doses ~ twofold greater required to elicit a positive response in PLA. CONCLUSIONS: COL blunts the prolonged exercise-induced decrease in clinically relevant in vivo immune responsiveness to a novel antigen, which may be a mechanism for reduced illness reports observed in the previous studies. These findings also suggest that CHS sensitivity is highly relevant to host defence.

Influence of 4 weeks of bovine colostrum supplementation on neutrophil and mucosal immune responses to prolonged cycling.

Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction. The aims of this study were to identify the effects of 4 weeks of COL supplementation on neutrophil responses and mucosal immunity following prolonged exercise. In a randomized double-blind, parallel group design, participants [age 28 ± 8 years; body mass 79 ± 7 kg; height 182 ± 6 cm; maximal oxygen uptake (V̇O2max) 55 ± 9 mL/kg/min] were assigned to 20 g per day of COL (n = 10) or an isoenergetic/isomacronutrient placebo (PLA; n = 10) for 4 weeks. Venous blood and unstimulated saliva samples were obtained before and after 2.5 h of cycling at 15% Δ (∼55-60% V̇O2max). A significantly greater formyl-methionyl-leucyl phenylalanine-stimulated oxidative burst was observed in the COL group compared with PLA group (P < 0.05) and a trend toward a time × group interaction (P = 0.06). However, there was no effect of COL on leukocyte trafficking, phorbol-12-myristate-13-acetate-stimulated oxidative burst, bacterial-stimulated neutrophil degranulation, salivary secretory IgA, lactoferrin or lysozyme (P > 0.05). These findings provide further evidence of the beneficial effects of COL on receptor-mediated stimulation of neutrophil oxidative burst in a model of exercise-induced immune dysfunction.

How Nordic Countries Enforce Impaired Driving Legislation.

This article reviews how the Nordic countries of Denmark, Finland, Norway, and Sweden enforce their legislation pertaining to driving under the influence of alcohol and/or other impairing drugs. The evidence necessary for a successful prosecution of traffic offenders has undergone radical changes over the past 50 years. The once widely used clinical tests of impairment are no longer a major element of the prosecution case and a physician is more seldom required to examine apprehended drivers and document any clinical signs and symptoms of alcohol and/or drug influence. These clinical tests have been superseded by results derived from a comprehensive toxicological analysis of psychoactive substances in samples of the driver's blood. The current statutory limits of blood-alcohol concentration (BAC) are among the lowest in the world: Norway and Sweden (0.20 g/kg) and Denmark and Finland (0.50 g/kg). Results from using evidential quality breath-alcohol instruments are accepted as evidence in drunk-driving cases and this has necessitated setting statutory breath-alcohol concentration (BrAC) limits. Laws dealing with driving under the influence of drugs (DUID) other than alcohol have also been updated and made more pragmatic for prosecution of traffic offenders. In Finland and Sweden zero-tolerance laws exist, making it illegal to drive with any quantifiable amount of a scheduled drug in the driver's blood. Prescription drugs are exempt from this zero-tolerance mandate provided the medication was used in accordance with a physician's ordination. Lacking a valid prescription or if there is a supratherapeutic concentration of the drug in blood, this will lead to a prosecution for DUID. In Denmark and Norway threshold concentration limits have been established for many psychoactive drugs, both licit and illicit. After these stricter laws for DUID were introduced, the number of suspects apprehended by the police per year increased by as much as tenfold in some Nordic countries. There is increasing evidence that many traffic delinquents in the Nordic countries suffer from a substance-use disorder, because repeat-offending is a common occurrence. This suggests that some type of treatment and rehabilitation program might be more beneficial compared with conventional penalties for people arrested for DUI and/or DUID.

Clinical and forensic toxicology of methanol.

Methanol has a very simple chemical structure (CH3OH) considering its potential health hazard, including the many poisoning deaths after ingestion. In countries where authentic alcoholic beverages are expensive, restricted, or banned for religious or other reasons, some people resort to purchasing alcoholic drinks made illegally. These clandestine sources of "booze" often contain high concentrations of methanol, added by the perpetrators to enhance potency and increase profits. Although an effective medical treatment for methanol poisoning exists, because most such incidents occur in socially deprived parts of the world, the hospital emergency facilities are scarce and/or inadequate. Trace amounts of methanol (median ~1.0 mg/L) are produced endogenously via certain enzymatic processes, such as one-carbon metabolism. Methanol and methyl esters are also contained in fresh fruits and vegetables as well as in alcoholic beverages. During a period of heavy drinking the blood-methanol concentration (BMC) increases and might surpass 10 mg/L, which is considered a biomarker for alcohol abuse and alcoholism. Methanol itself has a low intrinsic toxicity, but is converted in the body into two highly toxic metabolites, formaldehyde and formic acid. This metabolism is delayed by co-ingestion of ethanol, which creates a latent period of 12-24 h before toxic symptoms develop. Accordingly, when patients are admitted to hospital for diagnosis and treatment, a life-threatening metabolic acidosis has already developed and is irreversible. Symptoms of methanol poisoning include blurred vision, breathlessness, nausea, gastric pains, and acid-base disturbances and deficiency of oxygen in arterial blood. The visual disturbances might even develop into permanent blindness, owing to an interaction of toxic metabolites with the optic nerve. The minimum lethal dose of ethanol in humans is not easy to specify, because most poisonings involve co-ingestion of ethanol, which to some extent protects the patient from toxic sequelae. Effective antidotes for treatment of methanol poisoning are administration of ethanol or the therapeutic drug fomepizole (Antizol®), which is 4-methyl pyrazole (4-MP). Both treatments work by blocking the metabolism of methanol by liver alcohol dehydrogenase (ADH). The metabolic acidosis caused by the accumulation of formic acid in the body is treated with sodium bicarbonate, which helps to normalize pH in the bloodstream. Thereafter, methanol and its metabolites in the blood are removed by hemodialysis. However, the long-term prognosis for survivors of methanol poisoning is not good, because many are elderly males who are in poor health and often suffer from an alcohol-use disorder.

High Correlation between Ethanol Concentrations in Postmortem Femoral Blood and in Alternative Biological Specimens, but Large Uncertainty When the Linear Regression Model Was Used for Prediction in Individual Cases.

In connection with medicolegal autopsies peripheral blood (e.g. from a femoral vein) is the specimen of choice for toxicological analysis, although alternative specimens are also sometimes submitted, such as bile, cerebrospinal fluid (CSF), vitreous humor (VH), bladder urine, pleural effusions and/or lung fluid. Ethanol concentrations were determined in duplicate in femoral blood and in various alternative biological specimens by headspace gas chromatography. The analysis was carried out on two different fused silica capillary columns furnishing different retention times for ethanol and both n-propanol and t-butanol were used as internal standards. The results were evaluated by linear regression using blood alcohol concentration (BAC) as dependent or outcome variable and the concentrations in an alternative specimen as independent or predictor variable. The Pearson correlation coefficients were all statistically highly significant (P < 0.001); r = 0.94 (bile), r = 0.98 (CSF), r = 0.97 (VH), r = 0.92 (urine), r = 0.94 (lung fluid) and r = 0.96 (pleural cavity effusions). When the regression model was used to predict femoral BAC from the mean concentration in an alternative specimen the mean and 95% prediction intervals were 1.12 ± 0.824 g/L (bile), 1.41 ± 0.546 g/L (CSF), 1.15 ± 0.42 g/L (VH), 1.29 ± 0.780 g/L (urine), 1.25 ± 0.772 g/L (lung fluid) and 0.68 ± 0.564 g/L (pleural cavity effusions). This large uncertainty for a single new observation needs to be considered when alcohol-related deaths are evaluated and interpreted. However, the analysis of alternative specimens is recommended in medical examiner cases to provide supporting evidence with regard to the origin of ethanol, whether this reflects antemortem (AM) ingestion or postmortem (PM) synthesis.

Cooperative control of potassium accumulation by ouabain in vascular smooth muscle.

The effects of ouabain on potassium accumulation were studied in the dog carotid artery. It was confirmed that vascular smooth muscle lost potassium in the presence of ouabain greater than 10(-9) molar. This effect could be reversed by systematically increasing potassium in the external medium. The action of ouabain on ion accumulation was represented quantitatively with the application of a recent biophysical approach.

Concentration-time profiles of gamma-hydroxybutyrate in blood after recreational doses are best described by zero-order rather than first-order kinetics.

The recreational drug gamma-hydroxybutyrate (GHB) has a short plasma elimination half-life (t(1/2)) reported to be about 30-50 min. However, this represents a terminal half-life and therefore might not necessarily apply after large (abuse) doses are taken. Clinical studies with sodium oxybate (sodium salt of GHB) suggest that zero-order rather than first-order kinetics are more appropriate to describe post-peak concentration-time (C-T) profiles. We report the case of a 23-year-old male found unconscious by the police and a blood sample contained 100 mg/L GHB and 0.14 g% ethanol. On regaining consciousness the man admitted drinking alcohol about 6 h earlier but claimed that his drink must have been spiked with GHB. The police wanted to know how much GHB had been administered to account for the man's clinical condition. A back-calculation for 6 h, assuming a GHB half-life of 40 min, gives a very high concentration in blood of approximately 900 mg/L, which would probably have proven fatal. Back-calculating using zero-order kinetics and a proposed elimination rate of 18 mg/L per hour leads to a GHB concentration of 208 mg/L, which is much more realistic. Toxicologists should not arbitrarily apply the principles of first-order kinetics after abuse doses of drugs, when zero-order or saturation kinetics (Michaelis-Menten) are more appropriate.

Driving under the influence of psychoactive substances - A historical review.

Important events in the history of driving under the influence of alcohol (DUI) and/or other drugs (DUID) are reviewed covering a period of approximately 100 years. This coincides with major developments in the pharmaceutical industry and the exponential growth in motor transportation worldwide. DUID constitutes an interaction between the driver, the motor-driven vehicle, and one or more psychoactive (mind-altering) substances. In this connection, it is important to differentiate between drugs intended and used for medical purposes (prescription or licit drugs) and recreational drugs of abuse (illicit drugs). All chemicals with a mechanism of action in the central nervous system (brain and spinal cord) are potentially dangerous to use when skilled tasks, such as driving, are performed. The evidence necessary to charge a person with drug-impaired driving has evolved over many years and initially rested on a driver's own admissions and observations made about the driving by police officers or eyewitnesses. Somewhat later, all suspects were examined by a physician, whose task was to ask questions about any recent ingestion of alcohol and/or other drugs and to administer various clinical tests of impairment. By the 1940s-1950s, the driver was asked to provide samples of blood, breath, or urine for toxicological analysis, although the test results served only to verify the type of drug causing impairment of the driver. The current trend in DUID legislation is toward zero-tolerance or concentration per se statutes, which are much more pragmatic, because behavioral evidence of impairment is no longer a lynchpin in the prosecution case. This legal framework puts considerable emphasis on the results of toxicological analysis; therefore, the methods used must be accurate, precise, and fit for forensic purposes. Many traffic delinquents charged with DUI or DUID suffer from a substance use and/or personality disorder, with high recidivism rates. In addition to conventional penalties and sanctions for drug-related traffic crimes, many offenders would probably benefit from a medical intervention, such as counseling, rehabilitation, and treatment for substance use disorder, which often coexists with a mental health problem.

Relationship Between Postmortem Urine and Blood Concentrations of GHB Furnishes Useful Information to Help Interpret Drug Intoxication Deaths.

This article reports the concentrations of gamma-hydroxybutyrate (GHB) in femoral blood and bladder urine in a case series of drug intoxication deaths (N = 37). GHB was determined in blood (B-GHB) and urine (U-GHB) by a GC-FID-GBL method and 30 mg/L was used as a cut-off concentration for reporting positive results. The mean (median) and range of GHB concentrations in bladder urine were 2,818 mg/L (1,900 mg/L) and 120-13,000 mg/L, respectively. These concentrations were appreciably higher than those in femoral blood, 637 mg/L (260 mg/L) and 30-9,200 mg/L, respectively. Urine/blood ratios of GHB were highly variable (mean 8.99, median 5.33 and range 0.16-29.3). GHB is rapidly metabolized and cleared from the bloodstream, whereas there is no metabolism occurring in the urinary bladder. In five autopsy cases, U-GHB was lower than B-GHB, which suggests that these individuals died before equilibration of the drug in all body fluids and tissues. In the other 32 deaths, U-GHB was higher than B-GHB, sometimes appreciably higher, which points towards a longer survival time after intake or administration of GHB. The analysis of urine extends the window of detection of GHB by several hours compared with blood samples, depending in part on when the bladder was last voided before death. Furthermore, the urinary concentration of GHB gives a hint about the concentration in blood during the time that the urine was produced in the kidney and stored in the bladder since the previous void.

Physiologic effect of nifedipine and tamsulosin on contractility of distal ureter.

BACKGROUND AND PURPOSE: Renal colic not only leads to significant morbidity but imposes a financial burden on society in lost productivity and healthcare dollars spent. Both tamsulosin and nifedipine can facilitate spontaneous stone passage in the distal ureter and reduce the associated colic. We evaluated the physiologic effect of these agents on the distal pig ureter. MATERIALS AND METHODS: Bilateral ureters were removed en bloc with the bladder trigone from three pigs. Five-millimeter rings were taken from the intramural and distal ureter. Isometric tension recording was performed during both spontaneous and electrically stimulated contraction. Measurements of contractile interval and amplitude were taken in baseline buffer solution, nifedipine at 10(-6) g/L, and tamsulosin at 10(-6) g/L. Spontaneous contractile activity was also measured with phenylephrine at 10(-4) g/L followed by tamsulosin at 10(-6) g/L. RESULTS: Under conditions of spontaneous contractility, phenylephrine decreased the contraction interval by 46%, an effect which was reversed by tamsulosin. Tamsulosin increased the baseline interval by 27% (P < 0.025) and decreased the amplitude by 7% (P > 0.1). Nifedipine blocked all contractile activity. Under stimulated contractility, tamsulosin had no effect on the interval and decreased the amplitude by 7% (P > 0.1). Nifedipine blocked all contractile activity. CONCLUSIONS: We believe that both tamsulosin and nifedipine prevent the disorganized antiperistalsis associated with ureteral spasm while allowing some degree of antegrade fluid-bolus (stone) propagation. It is this mechanism of action that facilitates spontaneous passage and reduces associated renal colic when tamsulosin and nifedipine are used for the management of ureteral stone disease.

Decreases in blood ethanol concentrations during storage at 4 °C for 12 months were the same for specimens kept in glass or plastic tubes.

BACKGROUND: The stability of ethanol was investigated in blood specimens in glass or plastic evacuated tubes after storage in a refrigerator at 4 °C for up to 12 months. METHODS: Sterile blood, from a local hospital, was divided into 50 mL portions and spiked with aqueous ethanol (10% w/v) to give target concentrations of 0.20, 1.00, 2.00 and 3.00 g/L. Ethanol was determined in blood by headspace gas chromatography (HS-GC) with an analytical imprecision of <3% (coefficient of variation, CV%). Aliquots of blood were re-analysed after 2, 7, 14, 28, 91, 182 and 364 days of storage at 4 °C. RESULTS: The standard deviation (SD) of analysis by HS-GC was 0.0059 g/L at 0.20 g/L and 0.0342 g/L at 3.00 g/L, corresponding to CVs of 2.9% and 1.1%, respectively. The decreases in blood ethanol content were analytically significant after 14-28 days of storage for both glass and plastic tubes The mean (lowest and highest) loss of ethanol after 12 months storage was 0.111 g/L (0.084-0.129 g/L) for glass tubes and 0.112 g/L (0.088-0.140 g/L) for plastic tubes. The corresponding percentage losses of ethanol were 43-45% at a starting concentration of 0.20 g/L and 3.9-4.1% at 3.00 g/L. CONCLUSION: The concentration of ethanol in blood gradually decreases during storage at 4 °C. After 12 months storage the absolute decrease in concentration was ~0.11 g/L when the starting concentration ranged from 0.20 to 3.0 g/L. Decreases in ethanol content were the same for specimens kept in glass or plastic evacuated tubes.

Metabolic activation of AMP kinase in vascular smooth muscle.

AMP-activated kinase (AMPK) is a highly conserved heterotrimeric kinase that functions as a metabolic master switch to coordinate cellular enzymes involved in carbohydrate and fat metabolism that regulate ATP conservation and synthesis. AMPK is activated by conditions that increase AMP-to-ATP ratio, such as exercise and metabolic stress. In the present study, we probed whether AMPK was expressed in vascular smooth muscle and would be activated by metabolic stress. Endothelium-denuded porcine carotid artery segments were metabolically challenged with 2-deoxyglucose (10 mM) plus N(2) (N(2)-2DG). These vessels exhibited a rapid increase in AMPK activity by 1 min that was near maximal by 20 min. AMPK inactivation on return to normal physiological saline was approximately 50% in 1 min and fully recovered by 5 min. Immunoprecipitation of the alpha(1)- and alpha(2)-catalytic subunit followed by immunoblot analysis for [P]Thr(172)-AMPK indicates that alpha(1)-AMPK accounts for all activity. Little if any alpha(2)-AMPK was detected in carotid smooth muscle. AMPK activity was not increased by contractile agonist (endothelin-1) or by the reported AMPK activators 5-aminoimidazole-4-carboxamide ribofuranoside (2 mM), metformin (2 mM), or phenformin (0.2 mM). AMPK activation by N(2)-2DG was associated with a rapid and pronounced reduction in endothelin-induced force and reduced phosphorylation of Akt and Erk 1/2. These data demonstrate that AMPK expression differs in vascular smooth muscle compared with striated muscles and that activation and inactivation after metabolic stress occur rapidly and are associated with signaling pathways that may regulate smooth-muscle contraction.

Relation between blood- and urine-amphetamine concentrations in impaired drivers as influenced by urinary pH and creatinine.

Amphetamine undergoes extensive renal excretion and significant amounts are present in urine as the unchanged parent drug. This prompted us to investigate whether a quantitative relationship existed between blood and urine concentrations of amphetamine in the body fluids of drug-impaired drivers apprehended in Sweden, where this stimulant is the major drug of abuse. The relationship between blood and urine concentrations of amphetamine was determined by multivariate analysis with urinary pH and creatinine as predictor variables. Amphetamine was determined in blood and urine by gas chromatography-mass spectrometry with deuterium-labelled internal standards. The concentration of amphetamine in urine was about 200 times greater than the concentration in blood; the mean and median urine/blood ratios were 214 and 160, respectively, with large individual variations. The Pearson correlation coefficient between urine (y) and blood (x) amphetamine was r = 0.53, n = 48, which was statistically highly significant (P < 0.001), although the residual standard deviation (SD) was large (+/- 181 mg/L). The correlation coefficient increased (r = 0.60) when the concentration of amphetamine in urine was normalized for dilution by dividing with the creatinine content. When urinary pH and creatinine were both included as predictor variables, the correlation coefficient was even higher (r = 0.69), now explaining 48% (r2 = 0.48) of the variation in urine-amphetamine concentration. However, the partial regression coefficient for creatinine (53 +/- 28.7) was not statistically significant (t = 1.85, P > 0.05), whereas the corresponding regression coefficient for pH was highly significant and had a negative sign (-102 +/- 32.6, t= -3.12, P < 0.005). Other factors could impact on the urine-blood amphetamine relationship, such as route of administration, pattern of voiding and time elapsed after use of the drug.

Abnormally high concentrations of amphetamine in blood of impaired drivers.

We present a case series (N = 46) of individuals apprehended in Sweden for driving under the influence of drugs (DUID). These cases were selected because the concentrations of amphetamine in blood were abnormally high (> 5.0 mg/L), the highest being 17 mg/L. In comparison, the median blood-amphetamine concentration in a population of DUID offenders (N = 6,613) was 0.70 mg/L. Among the DUID suspects with extremely high blood-amphetamine concentrations there were 38 men (83%) with mean age of 37.8 y (SD 6.8 y) and 8 women (17%) with a mean age of 34.1 y (SD 4.3 y). All had previously been registered in our database (mean 12 times, median 9 times) for drug-related offences, including DUID. The concentration of amphetamine in blood of female offenders was slightly higher than the concentration in male offenders (6.6 mg/L vs. 5.8 mg/L), although this difference was not statistically significant (p > 0.05). The drugs other than amphetamine most frequently encountered in the blood samples were tetrahydrocannabinol and benzodiazepines (diazepam and nordiazepam). The commonest signs of drug use reported by the arresting police officers were bloodshot and glazed (watery) eyes, restlessness, talkativeness, exaggerated reflexes and slurred speech. Unsteady gait and dilated pupils were observed in some but not all individuals. These very high concentrations of amphetamine were tolerated without any fatalities indicating a pronounced adaptation to the pharmacologic effects of this central stimulant. Anecdotal information indicated that those with the very highest concentrations of amphetamine in blood had swallowed the drug to prevent being apprehended in possession of an illicit substance.