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Biomedical subjects

A Schmoldt

Publications and source records attributed to A Schmoldt.

At least 19 recordsLinked to original sources
PubMed2001

Death after excessive propofol abuse.

Abuse of the anaesthetic agent propofol (2,6-diisopropylphenol) is rare, but we report a case of a 26-year-old male nurse in which the autopsy showed unspecific signs of intoxication and criminological evidence pointed towards propofol abuse and/or overdose. Intravenously administered propofol is a fast and short-acting narcotic agent, therefore it seemed questionable whether the deceased would have been able to self-administer a lethal overdose before losing consciousness. The blood and brain concentrations corresponded to those found 1-2 min after bolus administration of a narcotic standard dose of 2.5 mg propofol/kg body weight. Extremely high propofol concentrations were found in the urine indicating excessive abuse before death. However, due to the short half-life of propofol, the cumulative effects of repeated injections should not be relevant for toxicity, since this would result in a blood level increase of only 1-2 micrograms/ml. Furthermore, the detection and quantitation of propofol in three different hair segments indicated chronic propofol abuse by the deceased. The results of the investigation suggest that death was not caused by a propofol overdose but by respiratory depression resulting from overly rapid injection.

Adult↗
PubMed2001

Lack of methemoglobinemia with flutamide.

OBJECTIVE: To determine whether the nonsteroidal antiandrogenic drug flutamide is a clinically relevant inducer of methemoglobinemia in patients with prostatic cancer. METHODS: Fifty consecutive outpatients with prostatic cancer stage D2 entered the study (age 71.1 +/- 7.3 y). Five patients were lost to follow-up; the remaining 45 patients received the recommended oral dose of flutamide 250 mg three times daily. Total hemoglobin (Hb) and methemoglobin (Met-Hb) concentrations were measured on varying days using an ultraviolet/visible-spectrophotometric method with an intra- and interday variability < 8%. In 12 patients, Met-Hb was analyzed before initiating flutamide therapy and after therapy was begun. RESULTS: On average, 2.6 venous blood samples per patient were analyzed with a mean Met-Hb concentration of 1.9% of total Hb. Mean concentrations of > or = 3% were detected in only six patients (13%). The data from 12 patients evaluated before and after initiating flutamide therapy were without significantly different changes. During the study period, no clinical signs of methemoglobinemia were reported or observed. CONCLUSIONS: This study found no clinically relevant increase of Met-Hb concentrations in elderly patients with prostatic cancer during chronic treatment with flutamide. However, clinicians should be aware of the very rare possibility of flutamide-induced methemoglobinemia.

Aged↗
PubMed2001

Contribution of nonsteroidal anti-inflammatory drugs to deaths associated with peptic ulcer disease: a prospective toxicological analysis of autopsy blood samples.

CONTEXT: Of the side effects occurring in temporal association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), peptic ulcer disease is reported most often. OBJECTIVES: To (1) provide information on the temporal association between fatal peptic ulcer presenting as sudden death and NSAID use prior to death, and (2) to examine the diagnostic efficiency of postmortem determination of NSAID levels using high-pressure liquid chromatography. DESIGN: Prospective autopsy study of all cases of sudden death associated with peptic ulcer disease from a total of 1139 medicolegal autopsies performed during a 12-month period. METHODS: Postmortem femoral blood samples were analyzed for NSAIDs using high-pressure liquid chromatography, and specimens of gastric and duodenal mucosa were examined for coexisting pathologic conditions. RESULTS: Twelve fatalities that occurred out of hospital as a result of peptic ulcer disease and presented as sudden death were identified. Autopsy blood samples were positive for NSAIDs in 7 cases (ibuprofen in 4 cases, levels 0.8 to 1.4 microg/mL; diclofenac in 2 cases, levels 0.6 and 1.6 microg/mL; and ketoprofen in 1 case, level 0.3 microg/mL). The ages of the affected individuals (3 men, 4 women) ranged from 43 to 60 years. No other drugs, including corticosteroids, anticoagulants, salicylic acid, and salicylates, were present. Microscopic examination revealed no pathologic antemortem mucosal conditions in any of the cases. CONCLUSIONS: For the postmortem elucidation of etiopathogenetic factors contributing to fatal peptic ulcer disease, high-pressure liquid chromatography to determine NSAID levels in autopsy blood samples is of considerable diagnostic benefit, especially when combined with histology. The number of cases of sudden death involving younger individuals dying as a result of peptic ulcer disease in temporal association with preceding use of NSAIDs seems to be underestimated from the clinical viewpoint due to the underrepresentation of out-of-hospital fatalities in the field of clinical pathology.

Adult↗
PubMed2000

Fatal intoxication with melperone.

Melperone is judged to be a safe neuroleptic drug. Until now there has been no report of a melperone fatality, though it has been used in suicide attempts. We report on a case of a 36-year-old woman where no cause of death could be established at autopsy. Criminological investigation pointed to a homicide by poisoning but also the possibility of a suicide had to be taken in account. The toxicological analysis of blood, cerebral spinal fluid and urine revealed extremely high concentrations of melperone which had never been reported before. Furthermore, diazepam, nordazepam and carbamazepine were detected. To our knowledge, this case is the first melperone fatality. Possible interactions with diazepam and carbamazepine are discussed.

Adult↗
PubMed2000

Methadone-related fatalities in Hamburg 1990-1999: implications for quality standards in maintenance treatment?

Drug-related fatal poisonings were analysed in Hamburg from 1990 to 30th June 1999 with special attention to the role of methadone. The first methadone-related fatalities were observed in Hamburg three years after methadone maintenance treatment (MMT) was introduced in 1990. Meanwhile more than half of all fatal poisonings among drug addicts are monovalent or polydrug intoxications with evidence for methadone. From January 1997 until June 1999 methadone was the predominant cause of death in about 39% of all drug-related fatal poisonings while the proportion of mixed heroin/methadone intoxications was about 10%. The rising problem of methadone-related fatalities goes with a decline of monovalent heroin intoxications which decreased in the last 9 years from 60% to 11%. Sixty-five per cent of those who died of fatal methadone-related poisonings had no history of MMT (60% of those with methadone as predominant cause of death). Since take-home doses for up to 7 days are prescribed to the patient due to a change in the German Narcotics Act in 1998, the diversion of methadone into illegal markets may have been accelerated. This results in rising numbers of non-intentional methadone-related fatalities among addicts who have never been in MMT. The prerequisites for the prescription of take-home doses should be taken more serious. There is no doubt that MMT reduced the mortality rate among the great majority of patients in Hamburg but supreme efforts should be made to prevent or reduce fatal intoxications by methadone in the non-treatment group.

Analgesics, Opioid↗
PubMed2000

Acute intoxication with aniline: detection of acetaminophen as aniline metabolite.

A 47-year-old woman unwittingly ingested an unknown substance together with her breakfast coffee. She suffered effects such as strong headache, generalized cyanosis, and a burning sensation of the lips and collapsed some minutes later. After admission into hospital a methemoglobin level of 35% was determined in the blood. Treatment by administration of tolonium chloride (toluidine blue) resulted in complete recovery of the patient. The toxic agent was identified as aniline by GC with mass selective detection after organic solvent extraction and 11 h after ingestion the plasma aniline level was 0.13 mg/l. Acetanilide (0.79 mg/ml) and acetaminophen (2.3 mg/ml) were identified in plasma as metabolites of aniline. It was assumed that a high metabolic capacity for acetylation protected the victim from more severe reactions. Her husband confessed later that he had tried to poison her.

Acetaminophen↗
PubMed1998

Body-packing as cause of unexpected sudden death.

Four fatalities related to smuggling of drugs by body-packing were investigated. The victims were examined at the Institute of Forensic Medicine of Hamburg University between 1983 and 1995, two of them due to "sudden" unknown cause of death. All victims were male. Two of them were found already dead in a backyard and in a hotel, two other were emergency cases and died at a hospital. Smuggled substances included cocaine (two cases), heroin and amphetamine/caffeine. In all cases, the cause of death was intoxication caused by torn packages which were detected at autopsy. The maximum weight of the packet's contents was 630 g divided in 90 packages. Only one victim was apparently an intravenous drug-abuser. Hair analysis was performed in three cases and revealed in one case a difference between a concealed and a habitually consumed drug. Toxicological analysis revealed that the substances were quite pure and provided evidence that rather long survival was possible following intoxication in three cases, in two cases supported by hospital treatment in the final stage. The procedural regimen in cases of suspected body-packing is discussed.

Adult↗
PubMed1998

A specific hydroxysteroid UGT is responsible for the conjugation of aliphatic alcohols in rats: an estimation of the importance of glucuronidation versus oxidation.

UDP-glucuronosyltransferase (UGT) activity for aliphatic alcohols was determined in microsomal liver fractions of Wistar rats. The rats were pretreated with inducers of cytochrome P450 and UGTs [phenobarbital (PB), beta-naphtoflavone (betaNF), and ethanol (10%)], and inhibition experiments with aliphatic alcohols and specific substrates for UGTs were performed to characterize the UGT form(s) responsible for the glucuronidation of aliphatic alcohols. Several UGT isoforms were purified from liver microsomes of low-androsterone-conjugating activity (LA), controls, and ethanol-pretreated rats by chromatofocusing and affinity chromatography. The results show aliphatic alcohols to be specific substrates for 17beta-hydroxysteroid UGT with considerable glucuronidation rates. This elimination pathway for aliphatic alcohols is not inducible by the tested inducers. Compared with kinetic data of oxidation, glucuronidation is probably the main elimination pathway for alcohols with a longer chain length than C3, especially when oxidation pathways are inhibited by the presence of proportionately high ethanol concentrations.

Alcohols↗
PubMed1997

Massive ingestion of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA).

OBJECTIVE: To report the course of a massive ingestion of the herbicide 2-methyl-4-chlorophenoxyacetic acid or MCPA (4-chloro-2-methyl phenoxy acetic acid) and to correlate plasma 2-methyl-4-chlorophenoxyacetic acid levels with symptoms of intoxication and treatment. CASE REPORT: After intentional ingestion of the herbicide, 2-methyl-4-chlorophenoxyacetic acid, a young man suffered burning in his mouth, spasmodic pain in the extremities and a severe hypotensive crisis. Plasma 2-methyl-4-chlorophenoxyacetic acid concentration was 546 mg/L two hours after ingestion. Therapy by forced diuresis was ineffective until the urine was alkalinized (Day 4). This resulted in a rapid decline of the plasma 2-methyl-4-chlorophenoxyacetic acid level to 6 mg/L and recovery of the patient.

2-Methyl-4-chlorophenoxyacetic Acid↗
PubMed1997

Therapeutic and toxic blood concentrations of more than 500 drugs.

In order to assess the significance of drug levels measured in clinical and forensic toxicology as well as for Therapeutic Drug Monitoring (TDM) it is essential that good collections of data are readily available. For more than 500 frequently used drugs therapeutic and, if data was available, toxic, and fatal plasma concentrations as well as elimination half-lives were compiled in a table. The compilation includes data for hypnotics like barbiturates and benzodiazepines, diphenhydramine, neuroleptics, antidepressants, sedatives, analgesics, antiinflammatory agents (e.g., NSAIDs), antihistamines, antiepileptics, betaadrenergic antagonists, antibiotics (penicillins, cephalosporins, aminoglycosides, gyrase inhibitors), diuretics, calcium-channel blockers, cardiac glycosides, antiarrhythmics, antiasthmatics, ACE-inhibitors, opiate agonists, and local anesthetics, among others. In addition, some toxicological relevant xenobiotics were listed. Data have been abstracted from published information, both compilations and primary sources and have been completed with data collected in our own forensic and clinical toxicology laboratories. Wherever possible, ranges for therapeutic plasma concentrations are expressed as trough concentration at steady state. The half-life values given for each drug are chosen to represent the terminal log-linear phase at most. It is the purpose to rapidly assess the significance of drug levels for the therapeutic monitoring of patients, and to facilitate the diagnostic assessment in case of intoxications.

Animals↗
PubMed1996

One fatal and one nonfatal intoxication with tranylcypromine. Absence of amphetamines as metabolites.

Two very different cases of overdose with tranylcypromine are presented. One clinical case involving the ingestion of 400 mg tranylcypromine with suicidal intention and one fatality with a suspicion of possible tranylcypromine overdose were examined. Both cases showed similar blood concentrations (0.5 and 0.7 mg/L, respectively), but the clinical case exhibited only mild symptoms of intoxication. The fatality showed no other drugs that could provide an explanation for the death of a 40-year-old male except tranylcypromine. Consideration of the drug concentrations in the fatality in relation to the case findings and other reported data indicates the tranylcypromine overdose as the probable cause of death, despite the low blood concentration. In addition, we looked for evidence of amphetamine as a putative metabolite in both cases. No amphetamines were detected in the overdose cases reported here.

Adult↗
PubMed1996

Three suicide attempts with moclobemide.

OBJECTIVE: To report plasma moclobemide, course and outcome of two cases of overdose with moclobemide alone and one case of combined ingestion of moclobemide and clomipramide. METHODS: Moclobemide identification and quantification was achieved by gas chromatography-mass spectrometry after alkaline extraction. CASE REPORTS: In case 1, plasma moclobemide was 2.8 mg/L with 1.8 mg/L clomipramide; in case 2, 18 mg/L; in case 3 60.9 mg/L and 4.6 mg/L 12 hours later. None of the patients showed serious effects during 24 hours of observation. Plasma moclobemide at 10 to 30 times therapeutic was not associated with major toxic effects. Moclobemide seems to be considerably less toxic than tricyclic antidepressants.

Antidepressive Agents, Tricyclic↗
PubMed1995

[Fatal vacuolar cardiomyopathy in chronic chloroquine drug treatment].

Clinical and morphological findings recorded in an 81-year-old woman patient with a 45-year history of rheumatoid arthritis treated with long-term chloroquine therapy are reported. The cause of death was low cardiac output syndrome, which upon autopsy and postmortem toxicological analyses was classified as vacuolar chloroquine-induced cardiomyopathy. The pathogenesis and the morphological and clinical characteristics of cardiotoxic effects of chloroquine are reviewed.

Aged↗
PubMed1994

[A compilation of therapeutic and toxic plasma drug concentrations].

In order to assess the significance of drug levels measured in clinical and forensic toxicology as well as for therapeutic drug monitoring (TDM), it is essential that good collections of data are readily available. For more than 400 frequently used drugs therapeutic and, if data were available, toxic and fatal plasma concentrations as well as elimination half-lives were compiled in a table including, e.g., hypnotics like barbiturates and benzodiazepines, neuroleptics, antidepressants, sedatives, analgesics, anti-inflammatory agents, antihistamines, anti-epileptics, beta-adrenergic antagonists, antibiotics (penicillins, cephalosporins, aminoglycosides, gyrase inhibitors), diuretics, calcium-channel blockers, cardiac glycosides, anti-arrhythmics, anti-asthmatics, angiotensin converting enzyme inhibitors, opioid agonists, and local anaesthetics. Data have been abstracted from published information, both compilations and primary sources, and supplemented with data collected in our own forensic and clinical toxicology laboratories. Wherever possible, ranges for therapeutic plasma concentrations are expressed as trough concentration at steady-state. The range of (or single) half-life values given for each drug are chosen to represent the terminal log-linear phase at most. In addition to the assessment of significance of drug levels for the therapeutic monitoring of patients, this list can assist the diagnostic assessment in cases of intoxication.

Drug Therapy↗
PubMed1994

Successful physostigmine treatment of acute dothiepin intoxication.

We report on a severe intoxication with the tricyclic antidepressant dothiepin. A treatment with a continuous infusion of physostigmine was successful and improved the ventricular arrhythmia. Dothiepin and its active metabolites were determined in plasma and urine by HPLC.

Adult↗