Intoxication Events Research Articles

Follow-up of skin manifestations in Yu-Cheng children.

We report an 11-year follow-up study on the dermatological manifestations of Yu-Cheng children born to mothers who were poisoned by polychlorinated biphenyl (PCB)-contaminated cooking oil between 1977 and 1979. Eighty-eight children born to these mothers, and 86 matched controls, were examined by one dermatologist. Chloracne scars were found in one patient, and there were nail abnormalities in about one-third of the exposed patients. Transverse grooves, irregular depressions, and koilonychia/nail flattening were significantly more frequent than in the control group, based on Fischer's exact test. This study indicates that in Yu-Cheng children the nail changes are the most persistent abnormality after PCB intoxication, and their occurrence may indicate developmental retardation of the fetal nail matrix. Such a finding might also suggest that PCBs remaining in the mother could exert an effect on nail growth in children born several years after the intoxication event.

Hexapropymate self-poisoning causes severe and long-lasting clinical symptoms.

Cases of hexapropymate poisoning requiring intensive care in an urban region of Sweden (420,000 inhabitants) were collected over 2.5 years (1985 to 1987). Only patients with serum hexapropymate concentrations above 5.5 mg/L (30 mumol/L) and with a negative history for intake of tricyclic antidepressants, phenothiazines, barbiturates, antihistaminic drugs and opiates were included. Clinical data about 8 intoxication events in 6 patients were evaluated retrospectively. Initial symptoms included coma, hypotension, hypothermia, and hypoventilation. Maximum coma depth (Glasgow coma score) was 3 to 5 in 5 out of 8 events. On 7 occasions assisted ventilation was required (for 12 hours or more in 5 events). There was no relationship between serum concentrations of hexapropymate and severity of clinical symptoms. All patients survived. Detailed analysis of the drug elimination in one patient showed a terminal elimination half-life of 21 hours, which is longer than previously reported (5 hours). The indications for use of this hypnotic drug may vary between doctors since an 8-fold variation was seen in drug prescription between Swedish counties in 1987. Poisoning with hexapropymate is a serious condition which may require symptomatic treatment in the intensive care unit. The clinical picture is similar to that seen in patients with burbiturate intoxication. There is no role for active forced elimination of the drug. It is questionable whether the clinical value of the drug is outweighted by its toxicity.

Ethanol regulation of adenosine receptor-stimulated cAMP levels in a clonal neural cell line: an in vitro model of cellular tolerance to ethanol.

The acute and chronic neurologic effects of ethanol appear to be due to its interaction with neural cell membranes. Chronic exposure to ethanol induces changes in the membrane that lead to tolerance to the effects of ethanol. However, the actual membrane changes that account for tolerance to ethanol are not understood. We have developed a model cell culture system, using NG108-15 neuroblastoma-glioma hybrid cells, to study cellular tolerance to ethanol. We have found that adenosine receptor-stimulated cAMP levels increased markedly upon acute exposure to ethanol. However, the cells became tolerant to ethanol, since chronically treated cells required ethanol to maintain normal adenosine-stimulated cAMP levels. Moreover, the cells appeared to be dependent on ethanol, as evidenced by reduced adenosine-stimulated cAMP levels in the absence of ethanol. Recovery occurred after ethanol was withdrawn. These cellular changes appear to parallel the clinical events of acute ethanol intoxication, tolerance, and dependence.

Acute and chronic effects of alcohol use on organizational processes in memory.

Subjects selected on the basis of their drinking histories (alcoholics, heavy drinkers, and social drinkers, N = 24) were tested on a series of tasks in order to assess organizational processes in memory. Each subject was tested twice: once while sober and once while intoxicated (blood alcohol level = 100 mg%). No systematic differences emerged as a function of drinking history, but results indicated that alcohol intoxication had several detrimental effects on memory performance. Intoxicated subjects recalled less information, had lower organizational scores, and learned at slower rates. Both storage and retrieval processes were adversely affected by alcohol, although retrieval processes were somewhat responsive to experimental manipulations. Findings are discussed in terms of the passive or unsystematic encoding strategies in intoxicated subjects that lowered the efficiency of their semantic organization and recall. Both clinical and experimental evidence suggest that memory impairments can occur as a result of alcohol intoxication. Reports have shown that alcoholics frequently experience blackouts or amnesia in connection with a drinking episode, and even nonalcoholics often have difficulty in remembering events that occurred during intoxication (Goodwin, Crane, & Guze, 1969). Several recent studies have shown that intoxicated subjects (both alcoholics and normals) are impaired in their ability to retain verbal material over short periods of time (i.e., 1 to 30 minutes), as well as in ability to recall the events of intoxication at a later time (Goodwin, Othmer, Halikas, & Freemon, 1970; Tamerin, Weiner, Poppin, Steinglass, & Mendelson, 1971). However, the same subjects are not impaired in their ability to recall material immediately after it has been presented. The general conclusion drawn from these findings is that alcohol produces a state in which short-term mem

1 Organophosphorus Pesticides: Pharmacology

Pesticides and agricultural chemicals are used to maintain an adequate food supply for the ever-increasing world population. A large number belong to the organophosphorus family and are biologically active against economically important parasitic pests. The organophosphorus compounds, currently in use, have a margin of safety between their effective use concentrations and their minimum toxic concentrations to mammals. However, it is always possible that mammals may become overexposed to these compounds or to toxic residues of these compounds following the application of excessive amounts to crops, either by hazard, by negligent handling or by intentional self-administration. A full understanding of the mechanism of their biological effects is therefore necessary so that these chemicals may be handled safely and effective remedies may be made available to counteract the effects of overexposure. The principal biological effect of organophosphorus chemicals in the mammalian system is the inhibition of cholinesterases. The pharmacology of the organophosphorus cholinesterase inhibitors has many facets. Much has been discovered concerning their mode of action and the therapeutic measures to be adopted in the event of intoxication by these compounds. The chapter summarizes recent developments in the understanding of the mode of action of the organophosphorus compounds in mammals.