Methadone toxicity causing death in ten subjects starting on a methadone maintenance program.

Methadone maintenance therapy is designed to reduce the need for addicts to use heroin or other illegal opiates. Death in patients starting on such a program has not previously been documented. We report the death of 10 persons who died within days of starting a methadone maintenance program administered by general practitioners. Their bodies were subject to a full autopsy by forensic pathologists, with a full toxicological examination. The mean starting dose had been 53 mg, which had been increased to a mean of 57 mg by the final dose. Death occurred after a mean of 3 days. The mean blood methadone concentration at death was 2.1 mumol/L. Complete toxicological analysis showed that six subjects had additional drugs present including two with alcohol, two with benzodiazepines and morphine, and one with benzodiazepines alone. Pathological examination revealed the presence of chronic persistent hepatitis in all subjects and bronchopneumonia in five. The causes of death were given as methadone toxicity or methadone toxicity in combination with bronchopneumonia. Our observations highlight the dangers of methadone in the first days of starting on a maintenance program, particularly when the starting doses are relatively high and subjects have no demonstrated tolerance to opiates.     

Positive and negative ion mass spectrometry and rapid isolation with Sep-Pak C18 cartridges of ten local anaesthetics.

The positive ion electron impact (PIEI), positive ion chemical ionization (PICI) and negative ion chemical ionization (NICI) mass spectra and a rapid isolation procedure using Sep-Pak C18 cartridges are presented for ten local anaesthetics. In the PIEI mode, molecular peaks were very small or missing for most compounds. Peaks at m/z 86 due to the diethylaminoethyl or propylaminoethyl group constituted base peaks in six compounds. In the PICI mode, peaks due to M + H and M + C2H5 appeared. The cation at m/z 86 was also observed for the six compounds. This ion seems useful for the screening of local anaesthetics. In the NICI mode, anions at m/z M - H constituted base peaks for all compounds, peaks at m/z M + 12 appeared in many compounds. The total ion current in the PIEI and PICI modes generally gave higher sensitivity than in the NICI mode. Local anaesthetics present in whole blood or cerebrospinal fluid (CSF) could be rapidly isolated by use of Sep-Pak C18 cartridges with chloroform/methanol as an elution solvent. Their detection was possible using wide-bore capillary gas chromatography with SPB-1 and HP-17 wide-bore capillary columns with satisfactory separation from impurities.     

Electrical and thermal injuries in pig skin — Evaluated and compared by light microscopy

The morphology of pig skin after electrical (el) and thermal exposure was studied in order to find methods applicable for disclosing electrical torture.Biopsies from pig skin exposed 24 hours earlier to either heat or electrical current under general anesthesia were studied by light microscopy. The amount of energy used of either type ranged from about 6 to about 100 joule deposited on two circular areas of the skin measuring 12 mm in diameter.In sections stained with hematoxylin and eosin alterations were found in heat-influenced specimens following the administration of moderate and large doses of energy. Changes were observed in el-influenced specimens also after the administration of low amounts of energy, which did not lead to macroscopical changes in the skin. The two types of energy induced different patterns of alterations inside the epidermis. The most characteristic change following heat exposure was the presence of a granular or fibrillar eosinophilic cytoplasm and subepidermal clefts, while el-expoure often produced white homogeneous cytoplasm and shadowy nuclei (“white necrosis”) in the attached epidermis. The individual changes could be produced by both types of injury, but to a highly different degree. However, the alteration classified as “vesicular nuclei” was only observed in el-damaged skin. The dermis from the more severely injured skin of both groups showed a homogeneous appearance (“necrosis”). While the changes of epidermis and dermis in response to heat were diffusely distributed, the changes created by electrical injury were often present in segments. By electrical damage homogeneous areas with loss of stainability and shadowy nuclei were occasionally observed in sweat glands, hair sheaths and in vessel walls, structures which are suggested to serve as conductors for the electrical current. “Vesicular nuclei” were observed in similar structures.Some of the findings may be associated with differences in intensity of energy during exposure to heat and electricity. Furthermore, the existence of different biological patterns following the two types of exposure should be considered. The studies are being continued to elucidate these basic questions, and to study further the medical diagnostic potential of examining skin biopsies from tortured individuals.