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Postmortem redistribution (PMR) refers to the changes that occur in drug concentrations after death. It involves the redistribution of drugs into blood from solid organs such as the lungs, liver, and myocardium. Drug properties such as volume of distribution, lipophilicity, and pKa are important factors. Basic, highly lipophilic drugs with a volume of distribution greater than 3 l/kg are most likely to undergo PMR. Examples include the tricyclic antidepressants, digoxin, and the amphetamines. The anatomical location of blood sampling can influence the drug concentration. The ideal site is a ligated or clamped femoral vein. Medical toxicologists participating in forensic cases involving drugs likely to undergo PMR must be aware of its potential contribution to the postmortem drug concentration. Correlation with laboratory data and any available antemortem or perimortem clinical information is necessary to render an appropriate opinion on the cause of death.

The safety, efficacy and pharmacokinetic parameters of 5 g of hydroxocobalamin given intravenously, alone or in combination with 12.5 g of sodium thiosulfate, were evaluated in healthy adult men who were heavy smokers. Sodium thiosulfate caused nausea, vomiting, and localized burning, muscle cramping, or twitching at the infusion site. Hydroxocobalamin was associated with a transient reddish discoloration of the skin, mucous membranes, and urine, and when administered alone produced mean elevations of 13.6% in systolic and 25.9% in diastolic blood pressure, with a concomitant 16.3% decrease in heart rate. No other clinically significant adverse effects were noted. Hydroxocobalamin alone decreased whole blood cyanide levels by 59% and increased urinary cyanide excretion. Pharmacokinetic parameters of hydroxocobalamin were best defined in the group who received both antidotes: t1/2 (alpha), 0.52 h; t1/2 (beta), 2.83 h; Vd (beta), 0.24 L/kg; and mean peak serum concentration 753 mcg/mL (560 mumol/L) at 0-50 minutes after completion of infusion. Hydroxocobalamin is safe when administered in a 5 gram intravenous dose, and effectively decreases the low whole blood cyanide levels found in heavy smokers.

Organophosphorus-induced delayed polyneuropathy (OPIDP) is initiated by the phosphorylation of a protein neurotoxic esterase (NTE) in the nervous system. A second step, the "aging" of the phosphoryl-enzyme complex, is required to produce the toxic effect. The experimental evidence for this molecular target and the importance of the aging process are reviewed. The catalytic activity of NTE has been used to develop an in vitro screening test that may distinguish the organophosphorus compounds (OPs) that cause neuropathy from those that do not, thereby providing a means for prevention of OPIDP. Moreover, a biochemical screening test, the determination of NTE activity in blood lymphocytes, may predict the development of OPIDP after acute or chronic exposure to OPs, and requires evaluation by carefully designed studies of occupational exposure to OPs.

Methanol poisoning is an uncommon but an extremely hazardous intoxication. Since methanol is a versatile fuel and is having increasing usage in an energy-conscious society, a high index of suspicion and swift laboratory confirmation is essential in managing this poisoning. Methanol poisoning may occur in sporadic or epidemic circumstances. Chronic exposure may occur in the occupational setting. Man is uniquely susceptible to methanol toxicity, perhaps dependent upon folate metabolism. Classic symptoms of methanol toxicity can only occur in laboratory animals who are rendered folate deficient. Folate may be useful in humans enhancing removal of the toxic products of methanol poisoning. The enzyme responsible for metabolism of methanol is alcohol dehydrogenase. Ethanol has a higher affinity for this enzyme and is preferentially metabolized. Simultaneous ethanol and methanol administration may confuse the onset of the intoxication. Pyrazoles may also be used to inhibit alcohol dehydrogenase thus preventing the intoxication. The most important initial symptom of methanol poisoning is visual disturbance. The symptoms may be delayed up to 24 hours after ingestion due to simultaneous alcohol administration and metabolic processes. Laboratory evidence of severe metabolic acidosis with increased anion and osmolar gaps strongly suggest the clinical diagnosis. There may be an important association between mean corpuscular volume which is significantly higher in cases of severe methanol poisoning than in mild cases.(ABSTRACT TRUNCATED AT 250 WORDS)

San Francisco bus drivers have an increased prevalence of hypertension. This study examined relationships between blood lead concentration and blood pressure in 342 drivers. The analysis reported in this study was limited to subjects not on treatment for hypertension (n = 288). Systolic and diastolic pressures varied from 102 to 173 mm Hg and from 61 to 105 mm Hg, respectively. The blood lead concentration varied from 2 to 15 jig/dL The relationship between blood pressure and the logarithm of blood lead concentration was examined using multiple regression analysis. Covariates included age, body mass index, sex, race, and caffeine intake. The largest regression coefficient relating systolic blood pressure and blood lead concentration was 1.8 mm Hg/ln (pg/dL) [90% C. I.,-1.6, 5.31. The coefficient for diastolic blood pressure was 2.5 mm Hg/ln (pg/dL) [90% C. I., 0.1, 4.91. These findings suggest effects of lead exposure at lower blood lead concentrations than those concentrations that have previously been linked with increases in blood pressure.

Although the toxic effects of lead have been known for centuries, lead intoxication is still widespread in the United States. Without baseline tests of neuropsychological, neurobehavioral and neurophysiological testing it may be difficult to detect subtle changes in neurological function after lead exposure. This may be further confounded by partial chelation treatment and exposure to neurotoxic mixtures or inability to quantitate alcohol consumption. We undertook a cross-sectional study to address these problems in 24 exposed and 29 control subjects in a plant that manufactured electrical components using fritted leaded glass to coat capacitors and transistors. Potentially exposed workers had blood lead levels ranging between 3 micrograms/dL to 135 micrograms/dL. Industrial hygiene monitoring revealed the plant's air lead levels ranged from 61 micrograms/m3 to 1,700 micrograms/m3 in excess of OSHA permissible exposure limits of 40 micrograms/m3/10 hr day. Using a specially designed battery of neurophysiological, neurobehavioral and neuropsychological screening tests, we demonstrated a significant difference from controls in measures of psychomotor speed, motor strength and verbal memory. Although limited by the cross-sectional design, these findings support the hypothesis that the battery of neurophysiological, neuropsychological and neurobehavioral tests can detect a significant inter-group differences between lead-exposed and control subjects.