Despite recent advances in the treatment of status epilepticus (SE), the mortality and morbidity associated with this condition remains high. Although the reasons for this excessive mortality are not known, several factors are suspected, including cerebral ischemia, cardiovascular collapse, toxic stimulation by neurotransmitters and hormones, or toxic products of intermediary metabolism. Cerebral lactic acidosis can cause cortical injury and has been shown to occur with seizures in experimental animals and in a limited number of human studies. We determined cerebrospinal fluid (CSF) and plasma lactate in 29 patients with generalized SE of diverse etiology. CSF was obtained within 12 h of termination of clinical seizure activity. The mean CSF lactate for all SE patients was elevated (3.74 +/- 0.31 mM) as compared with that of normal controls (1.60 +/- 0.10 mM) from non-neurologic patients undergoing spinal anesthesia. In patients who died or had a poor neurologic recovery, CSF lactate level was 5.36 +/- 0.58 mM (9 patients), whereas in 20 patients who showed good recovery CSF lactate level was 3.01 +/- 0.22 mM (p less than 0.005). The results demonstrate that SE causes a significant increase in CSF lactate and suggest that the magnitude of lactate elevation may serve as a predictive indicator of morbidity and mortality.
Effects of chronic dietary exposure to low levels of PCBs (polychlorinated biphenyls) on reproduction, growth and whole body burdens were investigated in three generations of Peromyscus polionotus. Mated pairs were maintained on a diet containing 5 mg/kg PCBs (Aroclor 1254) for 12 months, beginning exposure as young adults; matched controls received a similar diet without PCBs. Offspring were maintained on the parental regime and paired at maturity with non-siblings in the same group. In first and second generation offspring, birth and weaning weights were significantly lower in PCB-exposed animals; in the second generation, there were also significantly fewer mice born/month, longer intervals prior to birth of the first litter, and decreased survival to weaning (25 days) among exposed mice. Whole body residue of PCBs increased significantly with each generation of exposure. This study clearly shows that chronic exposure to PCBs at a dosage of 5 mg/kg depressed fertility, growth and survival in Peromyscus, and that these effects were amplified through multigenerational exposure.
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