Lorne K. Garrettson

Acute manic psychosis following the dermal application of N,N-diethyl-m-toluamide (DEET) in an adult.

Extensive animal testing and 30 years of human experience have established the general safety of DEET when applied episodically to skin or bedclothes. Local and systemic toxic and allergic reactions to DEET have been observed in man. Three weeks prior to admission, for the purpose of self-medication, a 30 year old man began daily applications of the insect repellant, DEET followed by a 1-2 hour period in a light-bulb heated box. Sedation and incoherence were noted for short periods following each application session. Aggressiveness and psychotic ideation led to hospital admission where he displayed psychomotor hyperactivity, rapid and pressured speech, tangentiality, flight of ideas, and grandiose delusions. Treatment was begun with haloperidol. Clinical improvement was complete within 6 days, atypical for classic endogenous mania. Drug and metabolites were identified in the urine more than 2 weeks after the last drug application.

Severe Central Nervous System Damage and Profound Acidosis in Persons Exposed to Pentaborane

Three cases of pentaborane intoxication resulting from a common exposure are presented. These cases were characterized by the rapid onset of seizures and opisthotonic spasms accompanied by severe metabolic acidosis without respiratory compensation. Rhabdomyolysis occurred, serum transaminase levels were elevated, and liver damage was demonstrated histologically. One patient died and another sustained severe neurologic damage. These poisonings are unique with respect to the rapid and devastating neurologic consequences. Pentaborane is an extremely toxic compound and a major hazard not only to exposed workers but also to the medical personnel dealing with them.

Subacute Chlordane Poisoning

A 30 year old female was exposed to chlordane through careless and excessive domestic use over a 1 to 4 week period. Early symptoms included circumoral numbness, anorexia, nausea, and fatigue. Myoclonic jerks occurred after a delay of one month. Malaise and anorexia became the dominant symptoms leading to referral at six months. Dysfunctional bleeding was attributed to hepatic enzyme induction by the chlordane and increased metabolism of contraceptive medication. Cholestyramine increased the stool elimination of chlordane.

Eighteen‐month follow‐up of neuropsychiatric effects of pentaborane intoxication

Fourteen individuals briefly exposed to the neurotoxic compound Pentaborane were reevaluated 18 months following initial neurpsychiatric study. Psychiatric interview utilizing standardized diagnostic criteria, neuropsychological and psychological assessment, and CT scan ventricular brain ratios were reevaluated. Assessment revealed interaction of bilogical and psychological factors worsening. Post-traumatic stress disorder, major affective disorder, alcohol abuse, and phobias were the most common diagnoses at follow-up.

Pharmacokinetic Modeling of Lead During EDTA Therapy

Mathematical simulation models for lead distribution in the body have been developed from studies of tracer lead administration to adults. These models do not predict the rebound of blood lead usually seen following chelation with EDTA. Children with elevated BLL were followed with daily blood assays during and for 6 days after chelation with EDTA, 50 mg/kg/d.Using a published model, a successful fit was accomplished only with increases in the size, and transfer rates of lead into and out, of shallow compartments. Initial conditions were determined by adjusting intake to mimic the observed BLL curve prior to reaching prechelation levels in selected patients. The model was constrained to fit the observed urine lead elimination during chelation. The deep compartment, (presumably cortical bone), is so deep, in pharmacokinetic terms, that it is not important to the rebound phenomena.Partial validation of our model will come if it continues to predict clinical response to EDTA. More effective chelation therapy is the major utility of such models.

365 DEVELOPMENT OF PHENOBARBITAL GLUCOSIDATION IN THE HUMAN NEONATE

Phenobarbital-N-glucoside (PNG) has recently been identified as a significant metabolite of phenobarbital (PB) in man. Glucosidation is an uncommon metabolic pathway for drugs in mammals. Bilirubin is glucosidated as well as glucuronidated. However, few xenobiotics have been recognized to be metabolized through this pathway.Four neonates treated with PB alone for seizures were studied. Serum concentrations ranged from 30 to 80 mg/l. Serial single daily voided urine specimens were analyzed for PB, PNG, and total p-hydroxyphenobarbital (PHPB). PHPB was first excreted on the 4th day of life in 2 patients and 10th day in 2. No PNG was detected by the 12th day in 1 case or 16th day in 2 cases. In the fourth case, the oldest by estimated gestational age, PHPB was first detected on day 4, and PNG on day 14. On day 20, PNG accounted for 50% of the drug excreted in the urine. Production of PHPB glucuronide was not assessed.It appears that N-glucosidation is a significant route for PB metabolism in the neonate. This pathway develops rapidly but after aryl hydroxylation.