Biomedical subjects

F Musshoff

Publications and source records attributed to F Musshoff.

At least 19 recordsLinked to original sources

PubMed2006

Results of hair analyses for drugs of abuse and comparison with self-reports and urine tests.

Urine as well as head and pubic hair samples from drug abusers were analysed for opiates, cocaine and its metabolites, amphetamines, methadone and cannabinoids. Urine immunoassay results and the results of hair tests by means of gas chromatography-mass spectrometry were compared to the self-reported data of the patients in an interview protocol. With regard to the study group, opiate abuse was claimed from the majority in self-reports (89%), followed by cannabinoids (55%), cocaine (38%), and methadone (32%). Except for opiates the comparison between self-reported drug use and urinalysis at admission showed a low correlation. In contrast to urinalysis, hair tests revealed consumption in more cases. There was also a good agreement between self-reports of patients taking part in an official methadone maintenance program and urine test results concerning methadone. However, hair test results demonstrated that methadone abuse in general was under-reported by people who did not participate in a substitution program. Comparing self-reports and the results of hair analyses drug use was dramatically under-reported, especially cocaine. Cocaine hair tests appeared to be highly sensitive and specific in identifying past cocaine use even in settings of negative urine tests. In contrast to cocaine, hair lacks sensitivity as a detection agent for cannabinoids and a proof of cannabis use by means of hair analysis should include the sensitive detection of the metabolite THC carboxylic acid in the lower picogram range.

Adult↗

PubMed2006

An automated and fully validated LC-MS/MS procedure for the simultaneous determination of 11 opioids used in palliative care, with 5 of their metabolites.

A fully validated liquid chromatographic procedure coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is presented for quantitative determination of the opioids buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, piritramide, tilidine, and tramadol together with their metabolites bisnortilidine, morphine-glucuronides, norfentanyl, and nortilidine in blood plasma after an automatically performed solid-phase extraction (SPE). Separation was achieved in 35 min on a Phenomenex C12 MAX-RP column (4 microm, 150 x 2 mm) using a gradient of ammonium formiate buffer (pH 3.5) and acetonitrile. The validation data were within the required limits. The assay was successfully applied to authentic plasma samples, allowing confirmation of the diagnosis of overdose situations as well as monitoring of patients' compliance, especially in patients under palliative care.

Analgesics, Opioid↗

PubMed2005

Spinal epidural haematoma after blunt trauma to the neck and hyperflection of the cervical spine.

Spinal epidural haematomas (sEDH) can be regarded as rare events, in principle a spontaneous and a traumatic aetiology can be distinguished. Spontaneous spinal epidural haematomas can arise, e.g. from vascular malformations, coagulopathies, etc. On the other hand, traumatic sEDH are related to, e.g. spinal trauma or intraoperative vascular injuries. With regard to clinical significance, spinal epidural haematomas accompanied by transient mild neurological symptoms up to lethal outcomes have been observed. We report on a 53-year-old male alcoholic who was found in the kitchen of his asylum in a grotesquely fixed body position, with his head and cervical spine in a maximum anteflected position. A general practitioner had ruled for a non-natural manner of death due to "broken neck" and alcohol intoxication, therefore, the prosecution authorities called for a medicolegal autopsy. At autopsy, paravertebral soft tissue haemorrhage in between the shoulder blades was disclosed. Furthermore, a spinal epidural haematoma, extending from the foramen magnum down to the middle portion of the thoracic spine was found. No fractures of vertebrae nor lesions of spine ligaments or bleedings of intervertebral discs were found. Blood alcohol concentration was determined 1.92 g/l and urine alcohol concentration was 1.76 g/l. Further morphological findings were cerebral oedema and cardiac hypertrophy; the urinary bladder was found filled to bursting. Neuropathological investigations confirmed the presence of the spinal epidural haematoma and assigned lethal significance to this finding. There were no histological signs of axonal injury. Reconstruction revealed that when sitting on a chair in a drunk condition, the individual's upper part of the body had fallen backwards in the corner and subsequently got stuck with maximum anteflection of the head and cervical spine, causing rupture of vessels and spinal epidural haematoma. Acute respiratory failure caused by impairment of the phrenic nerve following spinal epidural haematoma with potential synergism of alcohol intoxication was ascertained as the cause of death.

Alcoholic Intoxication↗

PubMed2004

Death during patient-controlled analgesia: piritramide overdose and tissue distribution of the drug.

We report about a fatality during patient-controlled analgesia (PCA). Piritramide peripheral blood concentration was measured with 0.1 mg/l and exceeded the normal therapeutic range. Therefore, a fatal overdose was considered as the cause of death with respiratory depression as the underlying pathophysiological mechanism. The tissue distribution was studied; highest concentrations of piritramide were measured in kidney, bile and urine. Due to a large volume of distribution a difference in the drug concentration found in heart and peripheral bloods the phenomenon of drug redistribution was observed. Confronted with toxicological results, investigations revealed, that the PCA pump had been changed during a previous servicing from displaying mg/h to ml/h, therefore, the anesthetist had entered "1.5" assuming mg/h, but actually applying 1.5 ml/h (which was therefore equivalent to 2.25 mg/h, given a concentration in the cartridge of 1.5 mg piritramide/ml). In total, 61.5 ml (instead of 61.5 mg) had been infused, equivalent to 92.25 mg piritramide. This case report is a further example that human errors can play a crucial role in the safety of medical equipment. Experts in anesthesia recommended human factors engineering design principles to improve the safety of medical devices.

Analgesia, Patient-Controlled↗

PubMed2004

Validated assay for the determination of markers of illicit heroin in urine samples for the control of patients in a heroin prescription program.

A fully validated procedure for the simultaneous determination of morphine (MOR), morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), 6-acetylmorphine (6AM), codeine (COD), codeine-6-glucuronide (C6G), acetylcodeine (AC), noscapine (NOS) and papaverine (PAP) based on liquid chromatography followed by electrospray mass spectrometry applying multiple reaction monitoring (LC-ESI-MS/MS) in urine samples is described. The extraction was carried out on a Zymark Rapid Trace Workstation using C18 solid-phase extraction cartridges. The separation was performed in 19 min on an Agilent 1100 HPLC system, using a Phenomenex C18 AQUA column (4 microm, 150 mm x 2 mm), which is coupled with an Applied Biosystems API 2000 mass spectrometer. Deuterated analogues were used as internal standards. The limits of detection were in the range of 0.1 ng/ml (PAP) to 7.4 ng/ml (M6G), the coefficients of correlation were higher than 0.996, the precisions ranged from 3% to 12% and the absolute recoveries were between 45% (M3G) and 98% (MOR). Analyses of samples from patients of a heroin prescription program demonstrated the usefulness of the procedure for the analytical differentiation between prescribed synthetic heroin (diamorphine) use and non-prescription heroin abuse on the basis of urine analysis. After the ingestion of pharmaceutical heroin only general markers for heroin use were detected, which are MOR, M3G, M6G and 6AM, respectively. When illicit heroin was abused, additionally to further general markers (COD, C6G) specific markers for non-prescription heroin abuse (AC, NOS, PAP) were found. However, it must be kept in mind that only AC may be regarded as absolute specific marker of non-prescription heroin, because all other compounds may appear in urine after ingestion of opiate alkaloids containing medicines or foods (e.g. poppy seeds). Therefore, patients of a heroin prescription program should be advised not to ingest such products.

Calibration↗

PubMed2004

Fatal blood and tissue concentrations of more than 200 drugs.

Fatal drug concentrations in body fluids and tissue samples are presented for more than 200 drugs and chemicals of toxicologic interest. Additionally, a reference list is added with more than 600 original papers concerning intoxications with a lethal outcome. The data can be helpful for the interpretation and plausibility control in own cases of intoxication. However, they should be used with caution, because use of drug data without sufficient knowledge about the patient or victim, the circumstances of the case, and about toxicokinetics and toxicodynamics might give a wrong interpretation in a special case.

Forensic Medicine↗

PubMed2004

Brain amino acid abnormalities in kidney disease and diabetes mellitus.

The present postmortem study examines whether specific amino acid abnormalities associated with renal diseases or diabetes mellitus in animal experiments and on clinical examination may also be found in human brain samples obtained at clinical autopsies. The material includes 12 deceased with renal insufficiency, 23 deceased with diabetes mellitus and 26 control cases with lethal cardiovascular diseases (without a history of hepatic, renal or metabolic disturbances). The autopsy and clinical records were retrospectively analyzed for age, sex, postmortem delay, cause of death, substantial preexisting diseases and histological findings. The analysis of free amino acid concentrations in human brain specimens was performed applying a Beckman amino acid analyzer. The results were evaluated using the U-test according to Mann, Willcox and Whitney. A P-value less than 0.05 was considered to be significantly different. Differences of amino acid concentrations attributable to sex, age and postmortem delay were not significant. The comparison of postmortem amino acid concentrations in the brains of patients with diabetes mellitus and controls did not reveal relevant changes. However, the patients with renal diseases, as compared to controls, showed a significant cerebral increase of urea, phenylethanolamine and gamma-aminobutyric acid. Thus, the postmortem amino acid analysis may contribute to the understanding of pathophysiological mechanisms of uremic encephalopathy and may supplement the conventional postmortem morphological diagnosis in kidney diseases by indication of functional impairment.

Adult↗

PubMed2004

Postmortem serotonin (5-HT) concentrations in the cerebrospinal fluid of medicolegal cases.

In a medicolegal study the postmortem serotonin (5-HT) cerebrospinal fluid (CSF) concentrations were determined in routine autopsies using a high performance liquid chromatographic procedure with electrochemical detection. There was no correlation between 5-HT concentrations and age, sex or blood alcohol concentration using a postmortem delay < or = 3 days. In suicides the suboccipital CSF concentrations were significantly decreased compared to the levels measured in the control group (8.55+/-5.99 ng/ml versus 20.15+/-13.56 ng/ml). Additionally, a decrease of 5-HT was found in the suboccipital CSF of opiate fatalities (15.56+/-13.52 ng/ml). The results support the hypothesis that decreased 5-HT concentrations in the CSF are characteristic in suicides. However, due to a rather broad overlapping of values between suicides and controls the results failed to define a possible cut-off level in the 5-HT CSF concentration to distinguish between a suicidal and a non-suicidal incident.

Adult↗

PubMed2004

MOR1 receptor mRNA expression in human brains of drug-related fatalities-a real-time PCR quantification.

The expression of the human micro-opiate receptor (MOR1) in post mortem human brain tissue was examined using real-time PCR technology. Tissue samples from 11 fatalities due to opiate overdose and five normal subjects with different causes of death were analysed in order to elucidate whether chronic opiate abuse is followed by a regulation of MOR1 expression. In each case nine selected brain regions (thalamus, caudate nucleus, hypothalamus, ventral tegmentum, hippocampus, amygdala, frontal cortex, nucleus accumbens, putamen) were evaluated. The MOR1-mRNA level was determined relative to the housekeeping gene beta2-microglobulin. While in most regions the MOR mRNA levels in the brain of addicts were not different from the control group-with varying levels between 0 and 15% of housekeeping gene level-in the brains of three drug-related fatalities an enormous increase was encountered in the thalamus where the MOR-mRNA level amounted for up to 10,000% of the measured housekeeping gene level. The results obtained by toxicological hair analysis in the group of drug-related fatalities indicate that the enormous thalamic MOR1-expression is primarily found in individuals who died from acute heroin overdose but did not show signs of a substantial chronic administration of the drug. Further studies have to be performed to evaluate if the observed MOR1-mRNA up-regulation in the thalamus in a subpopulation of acute lethal intoxications mirrors a state of functional hypersensitivity associated with the occurrence of death.

Adolescent↗

PubMed2003

Naphazoline intoxication in a child-a clinical and forensic toxicological case.

The imidazoline derivative naphazoline, an alpha(2)-adrenergic agonist, is used as non-prescription eye and nasal preparation because of its vasoconstrictive and decongestive properties. Especially in children, overdose and/or systemic side effects due to absorption can quickly cause severe central nervous system depression and cardiovascular adverse effects. In a 7-year-old boy was diagnosed a naphazoline intoxication by toxicological analysis. The case was also of forensic interest, because the naphazoline mixture was prepared in a pharmacy in a concentration 80 times above the adequate dosage for children. In general, physicians, pharmacists and the public should be educated about the toxicity of over-the-counter preparations.

Administration, Intranasal↗

PubMed2003

Simultaneous gas chromatographic-mass spectrometric determination of dopamine, norsalsolinol and salsolinol enantiomers in brain samples of a large human collective.

Using a solid-phase extraction procedure, an enantioselective derivatization and a gas chromatographic-mass spectrometric method, the levels of dopamine (DA) and of the dopamine-derived tetrahydroisoquinoline alkaloids (R)/(S)-salsolinol (SAL) and norsalsolinol (NorSAL) were determined in human brain samples. A complex pre-analytical synthesis of reference substances as well as deuterated internal standards allowed the standardized and reproducible analysis. In this study, to our best knowledge for the first time, the regional distribution of (R)-SAL and (S)-SAL, as well as NorSAL is examined systematically in a large collective of human brain samples obtained by autopsy. The material comprises 91 brains and 8 standardized specimens in each case. Anatomical concentration differences and no ubiquitous occurence were encountered. Significant amounts of (R)-SAL, (S)-SAL and NorSAL were only found in dopamine-rich areas of the basal ganglia, whereas in other regions of the brain no tetrahydroisoquinolines were detected. These findings suggest that the concentration of the substrate dopamine may determine the alkaloid level during in vivo formation. In our opinion, non-enzymatic formation of SAL via the Pictet-Spengler reaction reveals both the SAL enantiomers. An additional enzymatic synthesis of only (R)-SAL could explain the predominant occurrence of this enantiomer. Especially in the nucleus caudatus, the concentrations of DA, SAL and NorSAL decreased significantly with rising age, which may be consistent with apoptotic effects of ageing. Our data can serve as reference for other studies in humans concerning the etiology of alcoholism or other neurodegenerative diseases with the involvement of tetrahydroisoquinolines.

Adult↗

PubMed2002

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.

Accidents, Traffic↗

PubMed2002

Demonstration of a chloroquine fatality after 10-month earth-grave.

A 19-year-old woman suspect of a suicidal drug intoxication was exhumed after a 10-month earth-grave, because the police was accused of manslaughter and neglected help by the relatives of the deceased. Toxicologic analysis revealed as the cause of death an acute chloroquine intoxication. An expert opinion had to deal with the question if the woman would have been saved if the police had appeared earlier. Therefore the duration of agonal period after suicidal chloroquine ingestion was important. An estimation of the time since death was possible on the one hand ex-post from the development of cadaveric changes and supravital reactions and on the other hand, based on premortal changes detectable on the body together with the findings of the authorities. Taking into account all evidence the woman was probably already dead at or prior to the arrival of the police (110 min after ingestion), at least this could not be excluded. Chloroquine has to be considered to be useful for fatal poisoning, which is also recommended in some publications on methods to commit suicide.

Adult↗

PubMed2001

Fatality due to ingestion of tramadol alone.

A rare case of a fatal intoxication in an adult with tramadol alone is reported. In the peripheral blood, tramadol was measured in a concentration of 9.6 mg/l exceeded at least 30-times the normal therapeutic range of 0.1-0.3 mg/l. The concentration of tramadol in liver and kidney, in relation to blood, failed to suggest a major sequestration of drug in either specimen which is consistent with the volume of distribution of 3 l/kg. The concentration of tramadol in the heart and peripheral blood specimens did not suggest a major difference (ratio of 1.36). Similar to morphine tramadol was accumulated significantly in the bile.

Adult↗

PubMed2001

Numerical density of mu opioid receptor expressing neurons in the frontal cortex of drug related fatalities.

In animal and cell culture experiments, chronic morphine treatment has been followed by 'up'- as well as 'down-regulation' of the mu opioid receptor (mu OR) number. The present postmortem morphometric study of morphine-related fatalities of drug addicts (n=12, and 22-35 years old, with blood unconjugated morphine levels from 27.1 to 458 ng/ml, m.v. 198.5 ng/ml) versus a non-addicted control group (n=13 and 10-44 years old) was intended to examine whether chronic opiate exposure affects the numerical density of mu OR expressing neurons in the human neocortex (area 10 according to Brodmann). For the immunohistochemical procedure, thick (100 microm) vibratome sections were incubated with a monoclonal antibody against the mu OR [Arvidsson et al., J. Neurosci. 15 (1995) 3328] and immunoreactive sites were visualized using an immunoperoxidase protocol. The numerical densities of mu OR-expressing and Nissl-stained neurons were assessed morphometrically (camera lucida-drawings). In both collectives, the anti-mu OR immunoreactivity was mainly found in pyramidal neurons of layers (L) II/III and V and in multiform neurons of L VI. In the drug-related fatalities and the control group, the density of neurons expressing mu OR protein was similar, amounting for 2698 +/- 153 and 2688 +/- 172/mm(3), respectively. These findings extend the binding studies of opioid ligands in postmortem brains of heroin addicts [Gabilondo et al., Psychopharmacology 115 (1994) 135] revealing similar receptor densities and affinities by showing no difference in the density of mu OR-positive neurons.

Adult↗

PubMed2000

Numerical density of delta-opioid receptor expressing neurons in the frontal cortex of drug-related fatalities.

In animal experiment and in cell culture, chronic morphine treatment has been followed by a reduction as well as an increase of the delta-opioid receptor (OR) number. The present postmortem morphometric study of morphine-related fatalities of drug addicts (n=12, 22-35 years old, with blood unconjugated morphine levels from 27.1 to 407 ng/ml, m.v. 176.9 ng/ml) versus a non-addicted control group (n=13, 10-44 years old) is intended to examine whether chronic opiate exposure also affects the numerical density of deltaOR expressing neurons in the human neocortex (area 10 according to Brodmann (Vergleichende Lokalisationslehre der Grosshirnrinde (1909) Johann Ambrosius Barth, Leipzig)). For the immunohistochemical procedure, vibratome sections (100 microm) were incubated with a monoclonal antibody against the deltaOR diluted 1:100, and immunoreactive sites were visualized using an immunoperoxidase protocol. The numerical densities of OR expressing and Nissl-stained neurons were assessed morphometrically (camera lucida drawings). In both collectives, the anti deltaOR immunoreactivity was predominantly localized in pyramidal neurons of layers (L) II/III and V as well as in round and ovoid neurons of L VI. In the drug-related fatalities, the density of neurons expressing deltaOR protein amounted for 2515+/-240/mm(3), in the control group for 2616+/-204/mm(3), thus displaying no statistically significant difference. These findings go along with the binding behavior of opioid ligands in postmortem brains of heroin addicts revealing similar receptor densities and affinities in the control subjects and addicts.

Adolescent↗

PubMed2000

Hallucinogenic mushrooms on the German market - simple instructions for examination and identification.

'Magic mushrooms' is the name most commonly given to psychoactive fungi containing the hallucinogenic components psilocybin and psilocin. Material confiscated by local authorities was examined using morphologic, microscopic, microchemical, and toxicological methods. Psilocybe cubensis was the most popular mushroom in the sample collective, followed by Psilocybe semilanceata, Panaeolus cyanescens and Psilocybe tampanensis. The alkaloid content was determined with <0.003-1.15% of psilocybin and 0.01-0.90% psilocin. Panaeolus cyanescens was the mushroom with highest levels of psilocybin and psilocin.

Agaricales↗

PubMed2000

Determination of dopamine and dopamine-derived (R)-/(S)-salsolinol and norsalsolinol in various human brain areas using solid-phase extraction and gas chromatography/mass spectrometry.

Using a solid-phase extraction procedure and a gas chromatographic-mass spectrometric (GC/MS) method the levels of dopamine and the levels of dopamine-derived salsolinol (SAL) and norsalsolinol (NorSAL) were determined in human brain areas involved in the etiology of alcoholism, parkinsonism and other diseases. The possibility that biosynthesis of salsolinol occurs through a stereospecific enzymatic reaction was considered. Using a two-step derivatization with N-methyl-N-trimethylsilyltrifluoracetamide (MSTFA) and the chiral reagent (R)-(-)-2-phenylbutyryl chloride, baseline separated peaks of (R)- and (S)-SAL were obtained. Both enantiomers were found in human brain samples with no correlations between levels of salsolinol and dopamine. These findings do not support the hypothesis that only an enantio-selective synthesis of (R)-SAL by a putative salsolinol synthase is responsible for the in vivo formation. In our opinion, non-enzymatic formation of salsolinol via the Pictet-Spengler reaction reveals both salsolinol enantiomers and an additional enzymatic synthesis of only (R)-SAL explains the enantiomer ratio (R)-/(S)-SAL of approximately 2.

Adult↗