Search PubMed⌕ Search

Biomedical subjects

M A Howland

Publications and source records attributed to M A Howland.

31 records · Page 2Linked to original sources

Decreased plasma cholinesterase activity enhances cocaine toxicity in mice.

The illicit use of cocaine continues in epidemic proportions. Despite the incidence of life-threatening complications from cocaine use, little is known of the individual determinants of cocaine toxicity. In vitro analysis demonstrating that cocaine is poorly metabolized by the serum of patients with low plasma cholinesterase (PCh) activity (succinylcholine sensitivity) led to the hypothesis that altered PCh activity might modulate cocaine toxicity. An in vivo mouse model was created to test this theory. Mice were pretreated s.c. with either parathion [a mixed plasma and red blood cell cholinesterase (RBCCh) inhibitor], tetraisopropyl pyrophosphoramide (a selective PCh inhibitor) or placebo, and cholinesterase activity was determined at 24 hr. Incremental doses of i.p. cocaine were administered in a controlled and blinded fashion, and lethality was observed. Ten mg/kg s.c. parathion produced a mean suppression of 68 +/- 9 and 61 +/- 8% of PCh and RBCCh activity, respectively. One mg/kg s.c. tetraisopropyl pyrophosphoramide produced a mean suppression of 78 +/- 3 and 9 +/- 8% of PCh and RBCCh activity, respectively. Each pretreatment produced a statistically significant increase in cocaine lethality throughout the dose-response curve. Our results suggest that PCh activity is an important determinant of cocaine toxicity. This effect appears to be independent of either RBCCh activity or manifestations of organophosphate intoxication.

Animals↗

Theophylline desorption from activated charcoal caused by whole bowel irrigation solution.

Whole bowel irrigation with polyethylene glycol electrolyte lavage solution has been recommended as an adjunct to traditional overdose management. Although combined activated charcoal and whole bowel irrigation could enhance the efficacy of both modalities, this improvement remains largely speculative. An in vitro experiment was designed to determine whether polyethylene glycol electrolyte lavage solution alters the adsorption of theophylline to activated charcoal. Theophylline was agitated with activated charcoal in either water or polyethylene glycol electrolyte lavage solution, at each of three activated charcoal:theophylline ratios; 1:1, 3:1, and 10:1. The concentration in the supernatant was determined by high pressure liquid chromatography, and the maximal adsorptive capacity of activated charcoal for theophylline was calculated from the Langmuir equation. The percent of theophylline adsorbed by activated charcoal in water was 16 +/- 4%, 67 +/- 5%, and 97 +/- 3% for the 1:1, 3:1, and 10:1 ratios, respectively. This was decreased to 17 +/- 5%, 37 +/- 3%, and 62 +/- 2% when polyethylene glycol electrolyte lavage solution was added. A statistical difference (p less than 0.05) occurred at the 3:1 and 10:1 activated charcoal:theophylline ratios. Similarly the maximal adsorptive capacity was decreased 23% from 264 mg/g to 203 mg/g when polyethylene glycol electrolyte lavage solution was added to activated charcoal prior to theophylline. Polyethylene glycol electrolyte lavage solution significantly decreases adsorption of theophylline to activated charcoal in vitro. In vivo studies are required to confirm these findings. If activated charcoal is to be used clinically for theophylline toxicity, the authors suggest the possibility of larger quantities of activated charcoal, and administering activated charcoal in a slurry of water before the initiation of whole bowel irrigation.

Adsorption↗

Comparison of titratable acid/alkaline reserve and pH in potentially caustic household products.

Exposure to caustic agents is a common problem, affecting thousands of individuals annually. Despite this incidence, the factors responsible for the production of injury remain poorly defined. Although extremes of pH seem to correlate well with the production of esophageal lesions, pH alone fails to explain the damage resulting from exposure to agents with near neutral pH, such as soldering flux containing zinc chloride. We determined titratable acid/alkaline reserve (TAR) in 38 potentially caustic household agents. A subset of these products was evaluated in an in-vitro canine esophageal model to determine whether TAR correlated with esophageal injury. The results indicate that for the products evaluated TAR correlated better than pH with the production of caustic esophageal injury.

Animals↗

New York City's Poison Control Center: a systematic approach to a complex problem.

A pooling of public and private resources has created a regional poison control system which provides information and education to the medical and lay communities of metropolitan New York City. An overview of the poisoning problem on a national scale is followed by a description of the operations by the Center, and a special volunteer effort.

Drug Information Services↗

Anticholinergic poisoning.

Since the fall of 1979 numerous patients have been brought to emergency departments in New York City after being poisoned with an alcoholic beverage. On admission to the emergency services, they were noted to manifest significant anticholinergic toxicity. An analysis of the case histories, clinical presentations and laboratory data suggests that scopolamine eyedrops were deliberately used to poison these patients.

Adult↗