Human toxicology最新文献

A clinical and pharmacokinetic study was carried out progressively substituting a new anticonvulsant oxcarbazepine for its congener carbamazepine in a group of patients with refractory epilepsy. Although oxcarbazepine showed possible though not statistically significant advantages of better seizure control and was probably less sedating, its use was associated with a dose-dependent reduction in plasma sodium levels in 12 of 15 patients. The mean plasma sodium level fell from 137.5 +/- 5.2 (s.d.) to 128.5 +/- 6.1 mE/l. Imposed restriction of fluid intake may have minimized the degree of hyponatraemia. This adverse effect may limit the role of the drug as an anticonvulsant or necessitate special precautions when it is used. However, the possibility of employing the drug in diabetes insipidus may be worth exploring.

Eleven members of a family living in southeastern Turkey are presented. They were diagnosed as suffering from 'lead poisoning' with typical clinical manifestations and high blood lead concentrations. Contaminated flour (665 micrograms Pb/g) was the cause of poisoning, by oral ingestion. The source of contamination was sought and it was found that the stone of the mill had been repaired with molten lead on the same day that the wheat of the family had been ground; while grinding the wheat some lead was mixed into the flour.

Trimethyltin chloride was found to induce cytotoxic damage in vitro in human peripheral blood lymphocytes. Two concentrations (0.5 micrograms and 1.0 micrograms) were added to lymphocytes from male and female subjects in mitogen stimulated and serum supplemented culture medium for 72 h. A dose-related increase of inhibition of replication index (P less than 0.01) and cell division (P less than 0.001) was observed. The frequencies of abnormal cells and chromosomal aberrations such as chromatid and chromosome breaks, dicentrics, triradial and quadriradial configurations were increased significantly (P less than 0.001), as were micronucleus counts (P less than 0.001) and sister chromatid exchanges (P less than 0.001). Endoreduplication, an extremely rare spontaneous event in human lymphocytes, was observed in a few cases at all dose levels. The effects were more pronounced in lymphocytes obtained from habitual smokers.

1. We present a 40-year-old healthy man who developed a typical clinical picture of rhabdomyolysis following the administration of paraphenylenediamine by a witchdoctor as a pain killer. 2. Two groups of 15 mice were given paraphenylenediamine 70 mg/kg and 35 mg/kg respectively. Biochemical and histological findings of rhabdomyolysis developed in both groups, without kidney damage. 3. Paraphenylenediamine may cause rhabdomyolysis resulting in acute renal failure in humans. In mice, however, it produces rhabdomyolysis, but the kidneys are not affected.

1. Two fatal cases of deliberate self-poisoning with lignocaine are reported, one by oral ingestion and one by intravenous injection. Post-mortem blood lignocaine concentrations were 40 and 53 mg/l, respectively. 2. Lignocaine self-poisoning is rare since no formulations for oral use other than gels are available. However, serious toxicity can follow the oral application or ingestion of such gels, especially in children and in the elderly. Fatalities due to accidental oral overdosage with 10-25 g of lignocaine in adults have also been reported. 3. The frequent incidental occurrence of lignocaine in specimens submitted for toxicological analysis should not exclude the possibility of poisoning with this compound.

Toxicology results from all 302 coroners' cases referred to the supraregional unit at Beaumont Hospital over the one year period December 1987 to November 1988 are detailed. Clinical details were provided in 69.5% and formed the basis for the formation of four groups; road traffic accidents, suicides, possible suicides and possible carbon monoxide poisonings. All tests reported were instigated by the referring pathologist on behalf of the coroner. Alcohol was measured in all except 11 patients and a positive result was found in 44%. Drug screens were performed in 68.5% of cases with a positive finding in 30%. At least one positive result was found in 61.9% of the total. In the 60.4% of 53 road accident victims where alcohol was found, the median value was 117 mg/dl. COHb was measured in 23 cases and the median saturation was 45%. There were 12 suicides and agents found included paraquat, CO, cyanide, pancuronium bromide, and amitriptyline. Alcohol levels greater than 120 mg/dl were present in seven. In the 22 cases of suspected suicide, 77.3% were positive for drugs and more than one substance was found in 45.4%.

1. Sudden death is a recognized hazard of volatile substance abuse and may occur during exposure or in the subsequent hours. Intoxication may also lead to indirect deaths due to trauma. 2. Specific post-mortem features have not as yet been identified either macroscopically or microscopically in VSA-related deaths. Toxicological examination for volatile substances of all unnatural teenage deaths is strongly recommended. 3. Four mechanisms for acute, direct VSA-related deaths are discussed, viz anoxia, vagal inhibition, respiratory depression and cardiac arrhythmia. Of these, cardiac arrhythmia due to 'sensitization' of the heart to adrenaline is probably the most common and is well documented in experimental conditions. 4. Deaths from cardiac arrhythmia during or soon after VSA are unpredictable, unpreventable and resuscitation is rarely successful. Previous uneventful sessions of abuse provide no protection from this mode of death.

1. A scheme for the identification and evaluation of volatile substance abusers is outlined which emphasizes the need for medical history, drug history, emotional/behavioural and dependency questionnaires and physical examination. 2. Poor initial evaluation may lead to non-recognition of dependent abusers who may present later with more serious problems. 3. Suggestions for prevention and treatment of chronic abusers are discussed and some advice for parents is outlined.

1. Voluntary agencies fulfill a need by providing information on volatile substance abuse to schools, the parents/guardians of abusers and, last but by no means least, the abusers themselves. 2. Consideration of case file data from the period 1982-1987 shows that the average age of clients has dropped from 15.9 years (n = 70) to 13.3 years (n = 312) while the male:female ratio has dropped from 8:1 to 3:1. 3. In 1982, 80% of clients 'sniffed' glue but by 1987, 42% of new clients claimed to abuse butane and 23% aerosols. Of the 945 clients counselled, 41 have since suffered 'sudden sniffing death'. 4. Voluntary agencies can offer intensive, confidential counselling of abusers in an informed setting. It is hoped to extend the services provided outside the Greater London area and to provide residential care for those in need.

1. The main neurological disorders associated with chronic VSA are peripheral neuropathy, cerebellar disease, chronic encephalopathy and dementia. Apart from peripheral neuropathy, the clinical features are non-specific, evidence for solvent-related toxicity is in most cases circumstantial and there is no clear dose/response relationship. 2. Peripheral neuropathy is mainly associated with n-hexane and methyl n-butyl ketone. 3. Cerebellar disease is usually associated with toluene exposure; in the more severe cases there is often radiological evidence of irreversible cerebellar atrophy. 4. Chronic encephalopathy and dementia are the most serious consequence of solvent exposure, particularly to toluene in abusers and to mixed solvents in industrial workers. Postmortem studies in some abusers have shown generalized axonal degeneration, demyelination and brain atrophy. 5. Further studies on low level solvent exposure are needed as little is known about the neurological consequences of mild VSA, especially as regards individual susceptibility and possible interactions between solvents and other toxins such as ethanol.