Methadone and its role in drug-related fatalities in Cologne 1989-2000.

All drug-associated deaths from 1989 to 2000 were analysed at the Institute of Forensic Medicine in Cologne. Information concerning sex, gender, drug consumption, time, place and circumstances of death were analysed. A number of 605 cases were recorded; in 518 cases a toxicological analysis was possible and in 171 an autopsy was performed. When it was possible to determine the cause of death form the information available, acute drug intoxication was recorded in 65%. Heroin head the list of identified substances. Sixty-three percent of the specimens showed a combination of several substances, especially a combination of morphine, benzodiazepines, other medications and alcohol. In comparison with other studies the percentage of methadone-positive specimens is low, even though the proportion of specimens positive for methadone increased from 1989 to 2000. This analysis is discussed using background information concerning the management of substitution therapy and the available literature.

Sildenafil (Viagra): is there an influence on psychological performance?

BACKGROUND: Sildenafil (Viagra) is a well-introduced medicine for erectile dysfunction; many studies about effects and side effects are published. Beside these aspects of treatment the influence of sildenafil on psychophysical performance is of interest. cGMP is one of the most important second messengers in the central nervous system (CNS), so even very small changes of the intracellular cGMP-level caused by phosphodiesterases inhibition may be relevant for CNS-function. We wanted to verify the hypothesis whether sildenfail influences human psychomotor performance, especially under the aspect of traffic safety, or not. METHODS: Designed as a pilot study we tested 6 male healthy volunteers using a test battery of 7 different psychophysical performances tests. Each individual did the test battery twice, once without drug and once after a single oral dose of 100-mg sildenafil. 3 persons did the first and 3 others did the second experiment under the influence of drug (UID). All results (37 parameters) were analysed by t-test for paired samples using a confidence interval of 95%. RESULTS: Only two parameters of 2 different tests showed significant differences. In the simple choice reaction test (DR2) the mean reaction time got better in the group with sildenafil; in the multiple choice reaction test with stress induction (RST3) the amount of wrong answers indicated a weak influence of performance without statistical significance, six parameters (dominantly in the speed anticipation test (DEST)) represented an increase and one other (RST3 second part) showed a decrease UID. The uppermost parameters (76% of all items) stayed on equal levels for both groups. CONCLUSION: Sildenafil showed no important impairment of psychophysical performance, no strong improvement was found as well. With a look at the therapeutically indication of sildenafil the improvement in sexual activity may indicate no incapacity in traffic and other psychomotoric/psychophysical functions.

[Poisoning by perazine--organ distribution and interpretation]. / Intoxikation mit Perazin--Organverteilung und Interpretation.

A fatal intoxication of a 22-year-old woman after intake of the phenothiazine perazine is described. In all of investigated organs e.g. in liver, lungs and kidneys high concentrations of the active agent could be found. The analytical results lead to the assumption that at least 14, most likely 30 tablets of Taxilan 100 have been taken. An unintended overdosage seems to be excluded just as an administration by another person.

Comparison of nonradioactive microtiter plate enzyme immunoassays for the sensitive detection of fentanyl.

Fentanyl is a very strong opioid with analgesic properties that are approximately 80 times stronger than those of morphine and therefore is used in major surgery and treatment of pain in tumor patients. Cases of fentanyl abuse by intravenous injection, inhalation, oral or nasal application have been reported especially in the USA. Therapeutic levels of fentanyl are as low as 1 ng/ml of serum and therefore a screening test must have a detection limit below that concentration. Recently three non-radioactive enzyme immunoassays (EIAs) have become commercially available from COZART, STC and DIAGNOSTIX, all of them supplied by MAHSAN Diagnostika for evaluation with serum samples from forensic and clinical cases. A calibration curve is obtained with samples that contain 0, 0.1, 0.5, 1 and 5 ng fentanyl per ml of negative serum. The calibration curve of COZART is especially in the low range, steeper than those of STC and DIAGNOSTIX. The cut-off for all these EIAs, however, can be set at 0.5 ng/ml. After the administration of therapeutic doses, fentanyl concentrations were between 3 and more than 5 ng/ml as determined with the EIAs. The presence of the typical drugs of abuse, e.g. heroin, methadone, cocaine, cannabinoids and amphetamines including the derivatives of methylenedioxyamphetamine, don't generate false-positive results. No cross-reactivity was also observed at toxic levels of benzodiazepines and paracetamol and therapeutic levels of barbiturates, phenothiazines, antidepressants and analgesics. The EIAs tested so far appear to be suitable for the detection of fentanyl at therapeutic levels. False-positive results or cross-reactivity towards other compounds have not been observed.

Detection of psilocin in body fluids.

Active compounds of some mushrooms e.g. Psilocybe cubensis, Paneolus subalteatus or Stropharia coronilla, the psychotropic agents psilocybin and psilocin, have hallucinogenic effects. In one case of 'magic mushroom' intake, we had to analyse blood and urine. Psilocin was detected in the urine with REMEDi HS. Most of the psilocin was excreted as the glucuronide. Therefore an enzymatic hydrolysis should be the first step in analysis. Free psilocin was determined at a concentration of 0.23 mg/l while the total amount was 1.76 mg/l urine. The concentration of psilocin in serum was too low for detection with REMEDi HS. We proved a GC-MS-method with d(3)-morphine as internal standard and silylation with MSTFA. Similarly to urine, most of the psilocin in serum was found in the conjugated form. The concentration of free psilocin was 0.018 mg/l, that of total psilocin, 0.052 mg/l serum.

[Techno-festival mit fatal outcome]. / Techno-Festival mit tödlichem Ausgang.

The authors report on a 21-year old female who died suddenly during a techno-festival. The autopsy findings and the results of chemical-toxicological analyses were not able to clear up the cause of death. Pathophysiological and toxicological considerations demonstrate that only a combination of facts are sufficient to explain the sudden death of this young woman.

[Routine case of "auto-erotic accident"--surprising turn in evaluation of cause of death after chemical-toxicologic analysis]. / Routinefall "autoerotischer Unfall"--überraschende Wendung in der Bewertung der Todesursache nach chem.-tox. Analyse.

A man with indications of autoerotic manipulations was found dead in his flat and a homicide had to be excluded. Diverse material found in the flat suggested that the man was a consumer of cocaine. But the analyses of blood, urine and organs showed high concentrations of amphetamine and it was thought about an unintentionally mix-up with cocaine. A hair analysis was made and only amphetamine was detected. Therefore the utensils (mirror, razor-blade and sniff-pipe) belong to a rare nasal consumption of amphetamine.

[Protracted course of bromazepam poisoning in advanced age]. / Protrahiert verlaufende Bromazepam-Intoxikation im höheren Lebensalter.

HISTORY AND CLINICAL FINDINGS: A 68-year-old woman was found unconscious and hardly breathing. Artificial ventilation was undertaken by an emergency physician who brought her to hospital. Physical examination provided no evidence of relevant organ abnormalities. Neurological examination of the comatose patient revealed absent brain-stem reflexes and spontaneous respiration. But no other focal neurological abnormalities were found. INVESTIGATIONS: Routine laboratory tests, ECG, chest radiogram, Doppler sonography of arteries to the brain, lumbar cerebrospinal fluid and computed tomography of the skull were unremarkable. Toxicological tests discovered bromazepam intoxication (serum level 6 mg/l; maximal serum level after intake of 6 mg of the active constituent: 0.1 mg/dl). DIAGNOSIS, TREATMENT AND COURSE: When bromazepam poisoning was demonstrated elimination of the drug was no longer feasible; the spontaneous course of the poisoning with slowly falling drug levels could thus be observed over 10 days. In parallel with the fall of bromazepam concentration in blood, restitution of breathing and of brain-stem reflexes was recorded until, 12 days after intake of the drug, normal functions had been restored. CONCLUSION: Central respiratory arrest occurred at a bromazepam serum level of 6 mg/l. Without intensive medical care the patient would not have survived.

[Comparison of the MTP immunoassay with EMIT in blood screening for drugs]. / Vergleich der MTP-Immunoassays mit EMIT beim Screening von Blut auf Drogen.

We compared the MTP immunoassay with EMIT for the screening of drugs of abuse (opiates, cannabinoids, cocaine metabolites and amphetamines) in whole blood samples. These blood samples were obtained from the German police, when driving under the influence of drugs of abuse was suspected. For screening with the MTP immunoassay 25 microliters of serum or blood (without any pretreatment) was pipetted into the wells of the microtiter plates and the procedure was followed as described. Prior to screening with a Cobas Mira and EMIT reagents, the samples were treated with acetone to precipitate serum proteins. The cutoff for all drugs of abuse was set at 10 ng per ml of serum or blood. In most cases there was a good agreement between the negative and positive results of the two screening assays. The agreement between the two assays in the detection of opiates and cocaine was 91% and 93%, respectively, and for cannabinoids and amphetamines approximately 80%. The MTP immunoassay was more sensitive than EMIT for the detection of cannabinoids--but at the same time the MTP immunoassay was less specific. Both screening assays have a sensitivity of 100% for the detection of opiates and cocaine, but the specificity of the EMIT--also for opiates--was substantially lower. The MTP immunoassay has in respect to amphetamines a very high sensitivity, whereas the sensitivity of EMIT for amphetamines is inacceptable due to losses during sample preparation. The specificity of MTP immunoassay for amphetamines is not optimal, because a relatively large amount of samples tested false-positive for amphetamines at the cutoff of 10 ng/ml. In summary the MTP immunoassay, although not automated, performs well in comparison with EMIT, especially if the sample preparation for EMIT testing ist considered.

Combination of fatal digoxin poisoning with endocardial fibroelastosis.

This is the first report in the forensic literature of a combination of fatal digoxin poisoning with endocardial fibroelastosis (EFE). Typical morphological features of EFE as the cause of clinically diagnosed cardiomyopathy were present in the autopsy of a 3-year-old girl, including cardiac hypertrophy and marked thickening of the left-sided endocardium, consisting of numerous elastic and collagenic fibres. After exclusion of cardiac and cerebral causes of death, accidental digoxin intoxication was proved. Postmortem toxicological analyses by fluorescence polarization immunoassay (FPIA) disclosed digoxin levels of 71 micrograms/kg (femoral vein blood), 77 micrograms/kg (cardiac blood), 255 and 221 micrograms/kg (cardiac muscle of the right and left chamber), 163 micrograms/kg (psoas muscle), 91 micrograms/kg (lung), 222 micrograms/kg (liver) and 520 micrograms/kg (kidney). The results are compared with the antemortem digoxin concentration of 39 ng/ml serum. The case is discussed from its unusual morphological and toxicological aspects, with special consideration of possible medical malpractice.

[Two traffic accidents after heroin consumption with fatal outcome]. / Zwei Verkehrsunfälle nach Heroin-Konsum mit tödlichem Ausgang.

We report on 2 road accidents where 4 people--drivers and front-seat passengers--were injured so badly that they consequently died. All four had consumed heroin, in addition to which both passengers had also consumed cocaine and dihydrocodeine respectively. The blood samples of one of the drivers was only taken after the onset of intensive medical treatment including infusions and transfusions. Nevertheless the result of the analysis clearly showed that the driving ability had been impaired by heroin. In the remaining cases the opiat concentrations were so high that they could have justified a fatal intoxication in themselves. This applies especially to one of the passengers who displayed an unconjugated morphine blood concentration of 0.96 m/l. However, also in this case at the time of the accident the blood circulation and heartbeat did not stop immediately.

Hypoxanthine in vitreous humor and cerebrospinal fluid--a marker of postmortem interval and prolonged (vital) hypoxia? Remarks also on hypoxanthine in SIDS.

Hypoxanthine (Hx) is a degradation product of adenosine. Increased concentrations were reported in cases of hypoxia as well as with prolonged postmortem interval (PMI). Hx is recommended as an indicator of prolonged (cerebral) hypoxia, for example in vitamins of sudden infant death as well as a new biochemical method for estimation of postmortem time. The correlation of vitreous Hx values with the time since death was reported to be even higher than the vitreous potassium (K+) values. The authors' investigations on 92 bodies with known time since death gave a completely opposite result: a much higher correlation between vitreous K+ and time since death than vitreous Hx. The possible discrepancies between these different results will be discussed (disturbing of intra-ocular fluid dynamics by repeated sample-taking in the study of Rognum et al. The results published so far on vitreous Hx values in sudden infant death syndrome (SIDS) cases as an indicator for a prolonged cerebral hypoxia are also not convincing. When vitreous concentrations of newborn infants or infants of age < 6 months are compared to those of older infants or adults the vitreous diameter must be taken into consideration (diffusion gradient; Fick's law of diffusion). The discrepant results on vitreous Hx as a measure of vital hypoxia and PMI will be discussed. The authors' results on Hx determinations on cerebrospinal fluid in comparison to cerebrospinal spinal (CSF) potassium will also be briefly addressed.

[Drug fatalities with cadaver dumping]. / Drogentodesfälle mit Leichenbeseitigung.

7 cases of "dumping" of the bodies of drug addicts are reported. Circumstances of the case, findings at the scene, autopsy findings and confessions raised already the suspicion that the bodies were not found at the scene of death. In 5 cases the "dumping" of the bodies was outside, in 2 cases inside a house. Identification of the bodies was always easy, since personal papers (passport, identity card) were still present and no attempts were made to prevent identification. The prevalent motivation for "dumping" seems to be not to be identified as drug addict or dealer or to be brought in connection with the death of drug addicts.

[Plasma levomethadone level and concomitant use of sedatives in a methadone test program]. / Levomethadon-Plasmaspiegel und Beigebrauch von Sedativa im Methadon-Erprobungsprogramm.

Treatment of heroin addicts with levomethadone as an alternative to the clinically performed withdrawal gains in significance more and more. Just for that reason accompanying scientific programs guided along criterions of therapy research are essential. Results of an evaluation which is to be regarded as preliminary showed no correlation between methadone plasma levels and dosage. Additional consumption of opiates, barbiturates, and benzodiazepines was observed to a high degree. The efficiency of methadone treatment is to be valued only under consideration of criterions of admission to the program as for instance a drug abuse of many years or multiple unsuccessful treatments by withdrawal.

Failure of radiotherapy to resolve fatal lung damage due to paraquat poisoning.

The most effective treatment of severe paraquat poisoning in man is uncertain. In order to prevent pulmonary fibrosis, we employed radiotherapy of both lungs in a 23-year-old patient with severe paraquat poisoning; however, it failed to prevent the fatal outcome.

[Comparative studies of drug detection using recent immunologic methods]. / Vergleichende Untersuchungen zum Drogennachweis mit neueren immunologischen Methoden.

150 urine samples which we received from the criminal investigation department were measured with EMIT cannabis 20 and EMIT cannabis 50 reagents by EMIT Autolabsystem and especially with the immunoassay analyzer ETS by Syva Diagnostica. The confirming analyses were performed by GC-MS. If only cases are considered which are positive with cannabis 20 containing at least 10 ng 11-Nor-delta-9-THC-9-carboxylic acid in urine, there will be a negative result of 18.8% with EMIT 50. This appears to be unreasonably high. Some of these cases were also tested with Abuscreen ONTRAK-reagents. With this method the cut off for cannabis with 100 ng/ml urine is far too high but can be lowered essentially by taking a larger urine sample.

[Chemical-toxicologic studies of the epidemiology of drug use (1.)]. / Chemisch-toxikologische Untersuchungen zur Epidemiologie des Arzneimittelkonsums (1. Mitteilung).

During a long term program we secured when possible blood from a femoral vein of dead bodies. Until now 207 cases which were not selected have been investigated. The analyses were performed by high pressure liquid chromatography to prove extractable as well as by gas chromatography to determine volatile substances. These results are represented and correlated with the investigation of the CID or the Department of Public Prosecution respectively and with the results of autopsies if available and discussed.

Results of toxicological investigations of poisonings with atropine and scopolamine.

Lethal poisonings with alkaloids are rarely observed in the Federal Republic of Germany. We had however to investigate a case of poisoning with atropine and another with scopolamine during the last few years. The analysis was carried out with GC-MS and HPLC. Concentrations of the active substance on different organs of the body are represented. Thus the amount of alkaloid being taken is deduced. Cause of death is discussed by means of literature data.

[Comparison of various immunologic methods with a GC-MS analysis in cannabinoid detection in urine]. / Vergleich verschiedener immunologischer Methoden mit einer GC-MS-Analyse beim Cannabinoid-Nachweis im Harn.

60 urine samples which were sent within one month in order to be investigated on narcotic drugs were examined by means of 3 immunological methods EMIT, TDx and EIA (Roche) to prove cannabinoids and GC/MS procedure to investigate 11-Nor-delta-9-THC-9-carboxylic acid with 11-Nor-delta-8-THC-9-carboxylic acid as an internal standard. 50 of 51 cases which were proved to be positive by EMIT were confirmed by chromatography and were positive by the EIA method too. With TDx 40 of these cases corresponded one sample could not be measured. The applicability of the special immunological procedures to carry out quantitative analysis of the 11-Nor-delta-9-THC-carboxylic acid are presented.