A kinetic model describing the pharmacokinetics of ethyl glucuronide in humans

The glucuronide conjugation is a minor pathway of ethanol metabolism. The determination of ethyl glucuronide (EG) in serum and urine has gained importance in forensic and other legal decisions. To prospectively calculate the serum concentration of this non-oxidative ethanol metabolite, the computer program developed includes a parameter fitting routine. Multiple ethanol doses can be handled.The mathematical modeling was based on the following assumptions and simplifications, respectively. A single enzyme system is responsible for ethanol conjugation at one distinct site; the distribution of EG into the systemic circulation is delayed; the elimination of EG follows first-order kinetics.The concentration of EG was calculated using three kinetic parameters: a rate constant for the first-order formation of EG from serum ethanol, a transfer constant for an obstructed transfer of EG from the formation site (FS) into the central compartment (CC) and an exponential elimination constant.The program was applied to the data collected from 21 drinking experiments. The fitting algorithm optimized the three kinetic parameters, until the sum of concentration error squares of the data points was minimized. The means+/-standard deviation of the rate constant for the first-order formation of EG from serum ethanol was 0.0011+/-0.0006 h(-1), the transfer constant for an obstructed transfer of EG from the FS into the CC was 0.43+/-0.1996 h(-1) and the exponential elimination constant was 3.0+/-1.45 h(-1).Using the range of these parameters, it is now possible to calculate minimum and maximum serum concentrations of EG based on ethanol doses and drinking times. The comparison of calculated and measured concentrations can prove the plausibility of an alleged ethanol consumption. This can be crucial when the serum ethanol concentration (SEC) itself is not meaningful.     

An unusual case of driving under the influence of enflurane

An unusual case of driving under the influence of the volatile anaesthetic enflurane is reported. A markedly affected anaesthetist was sniffing at an enflurane-moistened handkerchief before he crashed into a lorry at a red traffic light. In the blood sample enflurane (2.92 mg/l) as well as diclofenac (0.28 mg/l) and 4-aminophenazone (24.4 mg/l) were found. The way of driving and the accident and the deficiency symptoms could be explained by the central suppressing effects of enflurane. The physician was considered as impaired and not suitable to drive at the time of the incidence.     

Analysis of dimethylamphetamine and its metabolites in human urine by liquid chromatography-electrospray ionization-mass spectrometry with direct sample injection

An analytical method to identify and determine dimethylamphetamine (DMA) and its metabolites in human urine was developed with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) involving the direct injection of a urine sample. The urine samples were directly injected by using a gel permeation column, whose stationary phase was polyvinyl alcohol with a small amount of a carboxyl group, so DMA and its metabolites were analyzed rapidly and simply without pretreatment such as extraction, concentration and derivatization. DMA and its metabolites were identified in drug-free human urine spiked with 1 microg of DMA, dimethylamphetamine N-oxide (DMANO) and methamphetamine (MA), and 3 microg of amphetamine (AM) in 1 ml of urine under the full-scan mode. Under the selected ion monitoring (SIM) mode, the limits of detection (signal-to-noise ratio=5) for DMA, DMANO, MA and AM were 20, 20, 20 and 60 ng in 1 ml of urine, respectively. This method was applied to the identification and determination of DMA and its metabolites in urine samples of 10 DMA abusers. The concentrations of DMANO were higher than those of unchanged DMA in all urine samples; thus, DMANO is considered to be a useful metabolite as an indicator to prove DMA intake.     

Use of the "SMITEST" PSA card to identify the presence of prostate-specific antigen in semen and male urine

To determine whether the prostate-specific antigen (PSA) could be identified in semen using the "SMITEST" PSA immunochromatographic membrane test card, we examined semen and other body fluids, including urine. Although PSA activity was detected in semen with high sensitivity using the "SMITEST" PSA card, it was also detected in adult male urine. However, the lower detectable limit in the urine was 1000-fold lower than that in semen. The concentration of PSA in adult male urine was found to be 800 ng/ml using the card. PSA activity usually can be detected in urine of individuals over 14 years old and it has been detected in urine from children as young as 11 years old. Therefore, the appearance of PSA in urine may occur anytime between the age of 12 and 14 years. To determine the stability of PSA activity in urine, dried samples of urine on filter paper were kept at room temperature for up to 3 years. Although the immunoreactive line showing PSA activity became weak after storage, it was still detectable, but faint, after 3 years. In addition, PSA activity was not detected in male serum or saliva and in the urine from human females, male cats or male dogs using the PSA card. We conclude that the PSA card is useful for identification of PSA in both semen and adult male urine.     

小机会孕育大事业

你认为自己已经具备了成为企业家的所有条件。你已经阅读了别人的成功故事，他们大获成功，这令你感到不安。你工作得很出色，人们总是说你前途无量，但是．你已经厌倦了接受平庸的人发出的平庸命令。而凡，为什么所有聪明的想法都是你的，但荣誉却总被别人得到？什么时候你能得到一次大幅提升——有可观的工资上涨．得到期权奖励和巨额奖金呢？“再等等，”他们总是说。“再等等。”是自己当老板的时候了。然而，如果你现在的工作舒适而安逸，每月定期领取工资，在现代化的办公室里工作．有一个高效率的秘书，还有一种在基础稳同的大公司工作的安全感．那么．住你辞上这份好工作之前，我有些告诫的话给你。     

DNA contamination by examination instruments

Using DNA-analysis systems in forensic examination, conditions without any (iatrogenic) contamination are necessary for analysis of evidence. Failing these conditions a contamination is possible and interpretation of the results may be difficult. Our experiments demonstrated a relevant transfer of DNA-material if contaminated instruments were used.     

Sex differences in proximal humeral outline shape: elliptical Fourier functions

A method is presented for the numerical analysis of sex differences in size and shape of the proximal humeral outlines using elliptical Fourier functions (EFFs). A skeletal sample consisting of right and left humeri pairs of 69 individuals, 36 males and 33 females, was used. The proximal superior view in the plane of the proximo-distal axis of each humerus was photographed and then 54 boundary points were located on the two-dimensional outline tracings. These points were digitized and used to compute EFFs with 27 harmonics. From the EFFs, a set of expected points on the proximal humeral outline was generated using the centroid as an origin. Superimposition of the male and female outlines on this centroid provided a detailed picture of the relative sex differences in size and shape with respect to that center. The bounded area of the proximal humeral outline showed statistically significant sex differences. Additionally, statistical results of the amplitudes derived from the "area-standardized" EFFs and visual assessments of the mean outline plots indicated significant sex differences in shape of the proximal humeral outlines. Focusing on localized regional differences, the greater tubercle was located more postero-medially and the lesser tubercle was located more anteriorly in the males compared to the females. Sex determinations from the proximal humeri were also examined with discriminant functions based on the amplitudes, which represent shape characteristics of the outline, and the hounded area. Using a cross-validation method, predictions of the percentages of cases correctly classified with the discriminant functions were ranged from 92.8% to 95.7% for the right and left humeral data. These results suggest that differences in size and shape of the proximal humeral outlines may be better predictors of sex when compared with conventional measurements of the humerus.     

Suicide by electrocution with low-voltage current

Three cases of suicide by electrocution with low-voltage current were observed in five years (1994-1998) by medical clinical forensic examiners of an Emergency Forensic Unit of the Paris suburb among 2,000 external death examinations. The cases involved one woman, aged 72 and two men, aged 38 and 41. In the last two cases, electric burns were retrieved under bared electric wires, placed on the arms or fingers in order to realize a hand-to-hand electric circuit involving the heart muscle. In the other case, the electric circuit between mouth and foot also involved the heart muscle. Household low-voltage current delivered (220 V in France) had a sufficient strength to induce local muscular paralysis and heart fibrillation. In the three cases, blood samples taken have retrieved very high levels of muscular enzymes (CPK, LDH) correlated to the mechanism of electric death. The rareness of suicide by electrocution and its forensic characteristics are detailed in order to help the clinical forensic examiners, prosecutors, and police officers concerned by such death examinations.