Justus v. Liebig and forensic toxicology.

Justus Liebig (1803-1873) was a renowned chemist, successful in many fields such as chemical analysis, agricultural chemistry, food chemistry, academic teaching and also forensic toxicology. He excelled in court in his role as an analyst and expert and appeared in extraordinary poisoning cases.

Acute bacterial meningitis as the cause of a traffic accident.

This is a report about a traffic accident without an apparent external cause. The driver responsible for the accident was diagnosed with acute bacterial meningitis. From a forensic aspect the meningitis was determined as the underlying reason for the accident, but it could not be assumed that the driver should have recognized the danger in time.

[Atypical "body packing syndrome"--a case report]. / Atypisches "Bodypacking-syndrom"--ein Fallbericht.

A case of ingested cocaine is reported in which death must be classified as body packer syndrome although both the temporal relationship and the number of packets were atypical. The deceased, a consumer of hard drugs who smuggled for his own use, was found in his flat. He was resuscitated and survived for another four days in hospital. Only four intact drug packages were found in the upper gastro-intestinal tract. The concentrations of cocaine in blood and organs were relatively low but in a potentially lethal range. The case is presented, and its particularities as well as the option of induced vomiting as a way of preventing the fatal outcome are discussed.

[Investigations concerning the threshold value between endogenous and exogenous GHB (liquid ecstasy)]. / Untersuchungen zum Grenzwert zwischen endogener und exogener gamma-hydroxybuttersäure (GHB/Liquid Ecstasy).

The article describes critical investigations concerning the threshold value between endogenous and exogenous concentrations of gamma-hydroxybutyric acid (GHB/"liquid ecstasy") in human blood. The values of GHB in the blood samples of 50 blood donors and 50 postmortem cases were measured with a validated gas-chromatographic/mass-spectrometric procedure according to the guidelines of the GTFCh (Society of Toxicological and Forensic Chemistry). GHB-concentrations were found to range between 0.11 and 1.56 mg/L (mean value 0.54 mg/L/standard deviation 0.37 mg/L/coefficient of variation 68.4 %) in the donors' blood, and between 2.2 and 116 mg/L (mean value 32.4 mg/L/standard deviation 25.6 mg/L/coefficient of variation 79 %) in the postmortem samples, respectively.

Reliability of the cloned-enzyme donor immunoassay (CEDIA) for cocaine in human serum in the range between the detection limit and the cut-off.

Immunoassays are used worldwide for the rapid screening of drugs. Despite the fact that they are highly valuable tools for the testing of legal and illicit drugs, there is a non-negligable risk of false-positive and false-negative findings and many pitfalls must be taken into account when using these tests in an uncritical manner and without valid confirmation procedures. In order to check the correlation between cloned-enzyme donor immunoassay (CEDIA) readings and exact determined gas chromatography/mass spectrometry (GC/MS) values for benzoylecgonine, a total of 472 serum samples was measured with an immunoassay (CEDIA) as well as GC/MS. As a result, it was shown that in the lower area of concentration, up to approx. 300 ng equ. benzoylecgonine/ml, there is a semiquantitative useful correlation. With higher concentrations, the values shift more and more apart and many runaways are visible. Generally the use of tests for materials other than those declared is excluded from the manufacturer's warranty and is at the user's own risk, but the authors found that many immunochemical tests with a certification only for the use in urine are well suited to the screening of serum samples, and even low readings could be confirmed by GC/MS. With blood or serum as sample, it could be regularly observed that generally very small readings could not only be confirmed with mass spectrometry but could in most cases also be quantified. This was the key factor in determining the rate of confirmation in 495 cases. In total, an incredibly high reliability for the CEDIA cocaine test (via benzoylecgonine) was shown up to the area of detection (detection limit), far below the cut-off. These results confirm the extraordinary sensitivity and specificity of this test also for blood or serum as sample material to be tested.

[The significance of the legal term "corpse" in forensic medicine]. / Zur Bedeutung des Leichenbegriffs für die Rechtsmedizin.

The definition of the term "corpse" is relevant for medicine in general and most particularly so for forensic medicine, as it has direct consequences on practical work: legally, postmortems and autopsies may only be performed on corpses. With this in mind, the legal term "corpse" was examined on the basis of German State Law regulations and provisions. Approximately half the burial acts include a definition of "corpse", but even here there are certain variations. The definitions for "corpse" can be divided into four categories: 1) according to the lack of vital signs or sure signs of death 2) according to the degree of decomposition and/or cohesion of body parts 3) on the basis of severed body parts, and 4) terminological differentiation of stillbirths and neonatal fatalities from miscarriages. Laws vary greatly in their definition of the term "corpse". Therefore, the decision whether or not human remains or parts thereof qualify as a "corpse" should be left to medical discretion.

[Drug screening in urine--common pitfalls in measurement and interpretation]. / Drogenscreening im Harn--häaufige Fehlerquellen bei der Messung und Interpretation.

Nowadays immunoassays are used for the rapid screening of drugs world-wide. Despite the fact that they are a highly valuable tool for the test of legal and illicit drugs, there is a non-negligible risk of false positive and false negative findings, and many pitfalls must be taken into account when using these tests in an uncritical manner and without valid confirmation procedures. In accordance with the committee for "problems of threshold values for medical and addictive drugs" set up by German scientific societies (in particular GTFCh, DGRM and DGVM), immunoassays are recommended as a useful tool for screening. But confirmation analysis with conclusive methods (GC/MS or LC/MS) is indispensable for valid substance identification, discrimination between active and inactive metabolites, detection of escort substances and accurate determination of concentrations in body fluids.

Immunoassays for drug screening in urine : Chances, challenges, and pitfalls.

Immunoassays are presently used worldwide for the rapid screening of drugs. Despite the fact that they are a highly valuable tool for the testing of legal and illicit drugs, there is a real risk of false-positive and false-negative findings and many pitfalls must be taken into account when these tests are used in an uncritical manner and without valid confirmation procedures. In a long-standing successful cooperation with a large psychiatric hospital, we checked doubtful and nonplausible immunochemical findings in urine with gas chromatography-mass spectrometry (GC-MS) confirmation methods. The reported case histories demonstrate typical pitfalls, for example, influence of changing nutritional habits, use of sweeteners (cyclamate), uncritical creatinine correction, impaired elimination, or cross-reactivities of simultaneous therapeutic medication. In accordance with national and international associations, immunoassays are recommended as a useful tool for screening. However, confirmation analysis with conclusive methods (GC-MS or liquid chromatography-MS) is unavoidable for valid substance identification, discrimination between active and inactive metabolites, detection of congeners, and accurate determination of concentrations in body fluids.

[The death of Kaspar Hauser (17 Dec 1833)--assassination, suicide or self-inflicted injury?]. / Todesfall Kaspar Hauser (17.12.1833)-- Attentat, Suizid oder Selbstbeschädigung? Rechtsmedizinische Betrachtungen.

The death of Kaspar Hauser is described taking present medicolegal and criminological knowledge into account, the main question being whether the injury was self-inflicted, homicidal or suicidal. In spite of a critical retrospective analysis this question cannot be answered with sufficient certainty even from our modern perspective. It seems unlikely that the stab to the chest was inflicted exclusively for the purpose of self-damage, but both a suicidal stab and a homicidal act (assassination) cannot be definitely ruled out.

[Reliability of % vol. declarations on labels of wine bottles]. / Zur Verlässlichkeit von Vol.-%-Angaben auf Weinflaschenetiketten.

The Council Regulation (EC) no. 1493/1999 of 17 May 1999 on the common organisation of the market in wine (Abl. L 179 dated 14/7/1999) and the GMO Wine 2000 (Annex VII A) stipulates that the labels of wine bottles have to indicate, among others, information on the sales designation of the product, the nominal volume and the alcoholic strength. The latter must not differ by more than 0.5% vol. from the alcoholic strength as established by analysis. Only when quality wines are stored in bottles for more than three years, the accepted tolerance limits are +/- 0.8% vol. The presented investigation results show that deviations have to be taken into account which may be highly relevant for forensic practice.

Pathogenesis of conjunctival petechiae.

Conjunctival petechiae from 15 cases (cause of death: different natural and unnatural) were analysed using confocal laser scanning microscopy (CLSM) in order to visualize the kind of the damage within the vessel wall (diapedesis versus rhexis). The pathomorphological findings with multiple ruptures of vessels appearing to be filled to bursting point define the conjunctival petechiae as a rhexis-haemorrhage.

[Deaths in preschool and school age--a retrospective analysis from a medicolegal point of view]. / Todesfälle im Vorschul- und Schulalter--eine retrospektive Analyse aus rechtsmedizinischer Sicht.

At the Department of Legal Medicine in Giessen all forensic autopsies from the years 1990 until 2001 were investigated under the aspect of "death in preschool and school age between 3 and 16 years of age." Out of 69 deaths 19% were due to a natural and 81% to an unnatural cause of death. Both groups (3 to 6 and 7 to 16 years of age) were analyzed retrospectively with regard to age and circumstances of death and compared with the literature. The purpose of the differentiating evaluation is to furnish ideas how to prevent violent deaths of children.

Munchausen syndrome by proxy (MSBP): an extreme form of child abuse with a special forensic challenge.

Munchausen syndrome by proxy (MSBP) is a special form of child abuse in which an adult repeatedly produces symptoms of illness in a person under his/her care. In most cases the perpetrators are mothers who repeatedly and in different ways produce or feign symptoms of illness in their children in order to obtain medical treatment for them. MSBP is thus a special form of child abuse that is also of importance in the field of forensic medicine and a particular challenge to the medicolegal expert. We report two cases of poisoning with different substances (clozapine and clonidine) detected by toxicological investigations at our Department of Legal Medicine. The relevance of the problem for the medicolegal expert and the importance of an interdisciplinary co-operation are pointed out.

Pitfalls of toxicological analysis.

Pitfalls are a permanent risk in all fields of forensic- and clinical-toxicological analysis and are not only concerned with immunoassays, although they are at present mostly discussed with regard to this subject. There are risks inherent in the field of preanalysis (e.g. the sampling, transportation, storage und treatment of the samples immediately prior to analysis). Furthermore, various pitfalls during measurement itself are to be avoided in connection with derivatization, choice of analysis parameters, memory-effects and many other sources of error. Another important section concerns the pharmacokinetic and pharmacodynamic interpretation of analytical results. Many toxicokinetic (e.g. enzyme induction) and toxicodynamic factors (e.g. tolerance effects) must be considered with special regard to plausibility controls (e.g. constellation, longitudinal, transversal and trend monitoring).

Postmortem in situ diagnosis of pacemakers and electrodes to detect dysfunction.

Cardiac pacemakers usually are very reliable, but sometimes malfunctions of the system occur. We conceived and developed a method to judge the functionality of pacemaker systems in deceased patients. The idea was to verify the hypothesis that more dysfunctions of implanted pacemaker systems go undetected than are detected and corrected. With the aid of a pre-amplifier and a digital storage oscilloscope, pacemaker pulse signals are derived from the surface of the thorax. The derived pulse shape offers information on the functionality of pacemakers and electrodes. Additionally the lead impedance is measured with a test pacemaker and its corresponding hand-held programmer. Synchronization properties can also be assessed with an external test pacemaker. So far 262 pacemakers have been investigated yielding an anomaly rate of 15%, comprising life threatening to annoying malfunctions. These results emphasize the forensic relevance and give reason for a discussion about the natural cause of death in these cases.

[Heteroplasmy in mtDNA in a set of dizygotic twins]. / Heteroplasmie der mtDNA bei einem zweieiigen Zwillingspaar.

The authors report on a case of a dicygotic female twin pair, one of them containing a T/C heteroplasmy in two (heart and brain) of five analysed organs at position nt204 of the HV2 region. Results and especially the evidence of an unequal distribution of the heteroplasmy are discussed.

[Immunochemical screening: manipulation, handling and interpretation errors, exemplified by benzodiazepines]. / Immunchemisches Screening: Manipulationen, Störungen und Fehlinterpretationen, dargestellt am Beispiel der Benzodiazepine.

The article describes problems related to immunochemical screening-tests with special regard to benzodiazepines, which are commonly used for therapeutic purposes. Focal points are adulteration, manipulation and handling of samples, the selection of cut-off-values, specificity and cross-reactivity, influence of biotransformation and frequently observed pitfalls in the interpretation of the analytical results.

[Screening and detection of amphetamine derivatives in biological stains]. / Screening und Nachweis von Amphetaminderivaten in biologischem Spurenmaterial.

A GC/MS-method is described for the screening, detection and determination of the commonly used drugs amphetamine, methamphetamine, MDA, MDMA and MBDB in small blood samples and bloodstains using solid phase SPE columns and a pipetting robot (Gilson Aspec XL). The detection limits are in the order of 0.03 to 0.08 microgram/L and the correlation factors between 0.9982 and 0.9998. Furthermore the stability was investigated covering a storage time of 64 days. The method has proven useful in forensic cases with only small sample volumes or bloodstains.

Studies of interferences of apomorphine and its metabolites or decomposition products with immunochemical screening tests for legal and illicit drugs after therapeutic doses of apomorphine.

This study deals with the question of whether apomorphine (CAS 314-19-2; e.g. in Ixense) and its metabolites or decomposition products interfere with the specificity of immunochemical screening tests (immunoassays) for legal and illicit drugs. It was the result of the investigations that after the therapeutic use of apomorphine no relevant false-positive screening findings were observed with the CEDIA (cloned enzyme donor immuno assay) and FPIA (fluorescence polarisation immuno assay) tests, which are commonly encountered in drug-screening programs, when using recommended cut-off values for urine.

Simultaneous screening and detection of drugs in small blood samples and bloodstains.

A gas chromatography-mass spectrometry (GC-MS) method is described for the screening and detection of morphine, codeine, cocaine, benzoylecgonine, methylecgonine, cocaethylene, delta-9-tetrahydrocannabinol (THC), 11-nor-9-carboxy-THC (THC-COOH), 11-hydroxy-THC (11-OH-THC), amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymetamphetamine (MDMA) and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in small blood samples and bloodstains using solid phase SPE columns and a pipetting robot (Gilson Aspec XL). The detection limits are in the order of 1.62-4.10 ng/50 microl spot (amphetamines), 0.15-0.82 ng/50 microl spot (cannabinoids), 1.67-4.70 ng/50 microl spot (cocaine and derivatives) and 4.53-4.91 ng/50 microl spot (opiates) and the correlation factors are between 0.9957 and 0.9999. The method has proven useful in forensic cases with only small sample volumes or bloodstains.