Sorption of fluoroacetate (compound 1080) by Colestipol, activated charcoal and anion-exchange in resins in vitro and gastrointestinal decontamination in rats.

The sorption of sodium fluoroacetate (FA) by activated charcoal (AC) and 5 anion exchange resins (AERs) was tested in 2 simulated gastrointestinal (GI) fluids. Each sorbent was incubated with FA in a shaker-water-bath at 37 C for 24 h. Supernatant was removed and filtered, and the concentration of FA was determined by gas chromatographic detection of the dichloroaniline derivative. Under simulated gastric conditions (0.1 M HCl at approximately pH 1.5), the sorbents removed the following proportions of FA from solution: Carbosorb AC, 87 +/- 2%; cholestyramine, 28 +/- 7%; colestipol, 96 +/- 0%; Amberlite IRA-96, 70 +/- 2%; DEAE-Sephadex, 7 +/- 4%; Chitosan, 66 +/- 2%. Under simulated intestinal conditions (0.05 M sodium phosphate at approximately pH 7.4), binding was as follows: Carbosorb AC, 68 +/- 4%; cholestyramine, 53 +/- 5%; colestipol, 46 +/- 2%; AmberliteIRA-96, 10 +/- 20%; DEAE-Sephadex, 64 +/- 7%; Chitosan, 5 +/- 2%. All findings differed significantly from control, with the exception of Amberlite IRA-96 and Chitosan in phosphate buffer, and DEAE-Sephadex in HCI. In a second study, rats were given 5 mg FA/kg, and then gavaged with 2 g/kg Carbosorb AC, colestipol or bentonite. Over 4 h, the area under the curve of serum FA versus time (AUC) decreased by 39% in the rats treated with colestipol and 42% in those treated with bentonite. In contrast, Carbosorb AC did not affect the AUC,yet increased Tmax In another study, mortality was assessed 96 h after rats were orally dosed with 5 mg FA/kg followed by gavage with 2 g/kg Carbosorb AC, colestipol or water immediatey or 30 min after dosing. When the sorbents were given immediately, mortality was the same as control (75%). Surprisingiy, the 30-min delay resulted in lower mortality in colestipol-treated rats, (approximately 38%) compared to 100% in the group treated with Carbosorb AC. Before any recommendation can be made regarding the use of colestipol as a GI decontaminant, the latter findings require confirmation in an intensive care setting. The potential for synergistic effects with 2 or more sorbents also warrant investigating.

Intentional self-poisoning with glyphosate-containing herbicides.

Four cases of self-poisoning with 'Roundup' herbicide are described, one of them fatal. One of the survivors had a protracted hospital stay and considerable clinical and laboratory detail is presented. Serious self-poisoning is associated with massive gastrointestinal fluid loss and renal failure. The management of such cases and the role of surfactant toxicity are discussed.

Management of oil of citronella poisoning.

The management for ingestion of oil of citronella, an essential oil, has traditionally been rigorous, including dilution with milk or oil, and gastric lavage or emesis, taking care to prevent aspiration. Recently our Centre handled five oil of citronella poisonings and their outcomes led us to review our management protocol which had been based on information from standard poisoning texts. The source data used to determine the human toxicity of oil of citronella and the appropriate management of poisoning included a case report of a fatal ingestion of oil of citronella in a child. On scrutiny, however, the management of this poisoning included now out-moded techniques, giving rise to uncertainties in establishing the true cause of the child's death. Our own experiences indicate that advice given in standard texts based on poisoning cases managed with out-moded techniques should be carefully evaluated.

Adiposity, lipids, alcohol consumption, smoking, and gender.

Indices of obesity, plasma lipids, and lipoprotein levels, plasma cholesteryl ester fatty acid composition, reported alcohol consumption and smoking habits were measured in 88 men and 87 women, ages over 15 years, randomly selected from the total respondents (1192) to a health survey. Most indices of obesity were related to plasma triglycerides and high-density lipoprotein levels in both sexes; to very low-density lipoprotein levels in men only; and to plasma cholesteryl ester fatty acid linoleic acid proportions in women only. The correlations with high-density lipoprotein cholesterol levels were dependent on very low-density lipoprotein triglyceride levels in men but not in women. Indices of obesity were significantly higher in nonsmoking women and reported alcohol consumption correlated with Quetelet's index (body mass index) in men. Smoking habits, but not alcohol consumption, influenced correlations between indices of obesity and plasma triglycerides and very low-density lipoprotein triglyceride levels in men. The present results showed several sex-related differences in relationships with indices of obesity. Lower very low-density lipoprotein levels, higher skinfold measurements, higher cholesteryl ester fatty acid linoleic acid proportions and lower alcohol intake in women than in men may be responsible. The data suggested that in women, altered diet composition may be linked with obesity.

The treatment of hyperlipoproteinaemia with gemfibrozil compared with placebo and clofibrate.

In a single-blind study the lipid-lowering drug gemfibrozil was compared at fixed dosage of 1600 mg daily with placebo and other drugs (mainly clofibrate) over a nine month period in 33 patients with hyperlipidaemia. Two patients were withdrawn from the study because of gastrointestinal symptoms attributable to gemfibrozil. The drug significantly lowered plasma cholesterol and triglycerides compared to the placebo. The drug also significantly lowered plasma cholesterol and triglycerides compared to the placebo. The drug also significantly lowered very low density lipoprotein (VLDL) triglycerides and raised high density lipoprotein (HDL) cholesterol levels but a previously significant inverse relationship between VLDL triglyceride and HDL cholesterol on placebo disappeared with gemfibrozil treatment.

Methanol monitoring. Comparison of urinary methanol concentration with formic acid excretion rate as a measure of occupational exposure.

Methods of monitoring occupational exposure to methanol were investigated in volunteer subjects who had ingested small amounts of methanol. It was confirmed that urinary methanol concentrations accurately reflected those in the blood. This relationship was maintained over a considerable range of concentrations in spite of large variations of urine flow. Concomitant ingestion of ethanolic beverages increased the urinary methanol concentration slightly. Urinary formic acid concentration was too variable to be of value but rate of urinary excretion of formic acid did reflect methanol uptake. The ratio of urinary formic acid to creatinine concentrations (F/C ratio) is a practical monitoring method. However, formic acid elimination rate is reduced by ingestion of ethanolic beverages. Urinary methanol concentration is favoured as a method of monitoring and a concentration of 10 microgram/ml measured at the end of the work shift is suggested as the level above which occupational exposure should be suspected and the appropriate action taken.

Lecithin:cholesterol acyltransferase activity, plasma and lipoprotein lipids and obesity in men and women.

Lecithin:cholesterol acyltransferase (LCAT) activity, lipid concentration, lipoprotein lipid concentrations and cholesteryl ester linoleic acid proportion were determined in the plasma of 85 subjects randomly selected from a population during a health screen survey. Mean fractional LCAT rate was significantly higher in men than in women. Molar LCAT rate correlated with low density lipoprotein (LDL) cholesterol concentration in men and with nearly all lipoprotein lipid concentrations in women. Most of these relationships were dependent on plasma unesterified cholesterol (UC) concentration. Fractional LCAT rate was correlated only with HDL cholesterol concentration in women and this relation was dependent on the influence of obesity. An inverse relationship between plasma cholesteryl ester (PCE) linoleic acid proportion and molar LCAT rate in women was also explained by influences of obesity on the data. Both fractional and molar LCAT rates were positively correlated with obesity (Quetelet's Index and subscapular skinfold thickness) in women but not in men. This study showed the influence of sex on nearly all correlations involving LCAT activity in combined groups of men and women.