Faculty Bibliography

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

In the brain, nitric oxide (NO) has been identified as a messenger molecule and a mediator of excitatory amino acid-induced neurotoxicity. In this study, the effects of NO on serum-induced mitogenesis and cell proliferation of the cerebellar glial cells were assessed. NO-generating agent, S-nitroso-N-acetylpenicillamine (SNAP) increased intracellular cyclic guanosine monophosphate (cGMP) levels. Furthermore, 2 chemically dissimilar NO-generating agents, SNAP and sodium nitroprusside (SNP) inhibited serum-induced thymidine incorporation and cell proliferation. The antimitogenic effect of NO was mimicked by 8-bromo-cGMP and blocked by hemoglobin, a known inhibitor of NO. The effect of NO was not cytotoxic, since the cells were not stained with Trypan blue and did not show increased release of lactate dehydrogenase in the culture supernatants. However, NO-treated cells showed decreased conversion of tetrazolium to blue formazan suggesting that NO inhibited mitochondrial activity in the glial cells. These results demonstrate that NO inhibits serum-induced mitogenesis and cell proliferation of cultured rat cerebellar glial cells

This article examines some current issues in toxicologic care. First there is a review of the scope of pediatric poisonings and some aspects of initial management. Then there is a discussion of the decision-making process required to properly use gastric decontamination in the management of poisonings. Each of the common methods available--emesis, gastric lavage, activated charcoal, catharsis, and whole bowel irrigation--is discussed. Finally, several new and old antidotes are reviewed, namely naloxone, glucagon, bicarbonate, dimercaptosuccinic acid, digoxin-specific fab fragments, and flumazenil

The effect of bretylium tosylate on plasma catecholamines and on electrically induced arrhythmias was evaluated in anesthetized hypothermic dogs. Bretylium at a dose of 7.5 mg/kg was administered prior to cooling from 37 degrees C to 27 degrees C. During cooling, the ventricular arrhythmia threshold (VAT) in control animals decreased from 10.1 +/- 1.9 to 4.4 +/- 1.3 impulses, while the VAT in bretylium-treated animals increased from 9.8 +/- 2.9 to 23.2 +/- 2.7 impulses. Catecholamine levels increased during cooling in all animals. In control animals, the epinephrine/norepinephrine ratio was unchanged, but in animals treated with bretylium tosylate, the ratio increased more than 10-fold (from 0.48 +/- 0.1 to 5.49 +/- 0.32 at 29.9 degrees C). The demonstrated increase in catecholamine levels during hypothermia suggests that the protection offered by bretylium tosylate against cardiac arrhythmias is not explained by modification of catecholamine levels, and is more likely due to an alteration of the electrophysiologic properties of cardiac tissues

STUDY OBJECTIVE: To determine the reliability of a recently developed electrochemical meter to rapidly (within 60 seconds) measure blood alcohol concentration (BAC) in the emergency department. DESIGN: A prospective study comparing the meter data with that of immunoassay and gas chromatography criterion standards undertaken during a ten-week period. SETTING: Adult ED of a municipal hospital. PARTICIPANTS: Three hundred eighty-three consecutive patients with altered mental status or suspected alcohol intoxication. INTERVENTIONS: Each patient underwent routine phlebotomy, and blood samples were obtained for meter and immunoassay BAC determinations. The first 60% of patients also underwent gas chromatography BAC determination. RESULTS: Two hundred nineteen patients (60%) had BAC detectable by both meter and immunoassay. BAC measurement by the meter correlated strongly with immunoassay and gas chromatography determinations (Pearson's correlation coefficient, r = .94; P less than .00000001 for both correlations). CONCLUSION: The electrochemical meter provides a rapid and reliable BAC measurement in the ED

STUDY OBJECTIVE: To determine whether plasma cholinesterase (pseudocholinesterase) activity is a marker for severe cocaine toxicity. DESIGN: A prevalence study in a cohort of cocaine users. SETTING: A large urban emergency department. PARTICIPANTS: During a three-month period in 1989, 187 patients who presented to the ED on 191 consecutive occasions with signs and symptoms consistent with cocaine intoxication were prospectively enrolled in the study protocol. METHODS AND MEASUREMENTS: All patients had plasma cholinesterase activity determined by the electrometric method. The patients who were cocaine positive were stratified into one of two groups: life-threatening toxicity (LT) and non-life-threatening toxicity (NLT), based on a predetermined set of criteria. Cocaine-negative patients served as controls for the LT group if criteria were otherwise met. RESULTS: Mean (+/- SD) plasma cholinesterase activities for the LT, NLT, and control groups were 682 +/- 277, 904 +/- 279, and 1,058 +/- 385 Michel units/L, respectively. All three groups were significantly different from each other (P less than .05 by analysis of variance). CONCLUSION: The data suggest that decreased plasma cholinesterase activity is associated with increased risk of life-threatening cocaine toxicity