Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article reports an investigation into the vestibuloocular reflex (VOR) recorded in rats during acute nontoxic treatment with phenytoin (PHT). In animals adapted to the dark, latency and duration of postrotatory nystagmus (VAN), cumulative trend of slow phases (CTSP), slow-phase velocity, temporal trend of the frequency and amplitude of the nystagmic beats, and mean frequency-amplitude ratio were analyzed. Observations were correlated with plasma and brain levels of the drug. Results showed that an acute nontoxic dose of PHT impairs some parameters of the VAN. At low concentrations (8.24 +/- 2.56) (microgram/ml in plasma and 6.02 +/- 3.24 micrograms/g in brain), only CTSP and slow-phase velocity were remarkably modified in each animal. At higher concentrations but still subthreshold for evoking the appearance of evident signs of drug toxicity (17 +/- 6.13 micrograms/ml in plasma and 11.4 +/- 5.28 micrograms/g in brain), all parameters were modified in each animal. In the same animal, VOR impairment was always linearly correlated to the plasma and brain drug levels. A considerable individual biovariability in the drug response appeared, and an individual subtoxic threshold for each animal was evident. Thus, when results of all experiments were averaged, the statistical significance of the differences of the greater part of the VOR parameters disappeared. However, VOR analysis performed before and after drug administration, i.e., with each subject as its own control, proved to be an excellent diagnostic pointer to the approach of the particular subject's toxic threshold before the appearance of spontaneous nystagmus or postural impairments.
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PMID:Postrotatory nystagmus during phenytoin treatment. 372 Jun 97

Experimental studies have shown that dextromethorphan, a noncompetitive N-methyl-D-aspartate antagonist is neuroprotective in experimental models of ischemic cerebral injury. The authors studied the safety and tolerability of oral dextromethorphan (DM) in humans, and correlated serum levels of this drug with cerebrospinal fluid (CSF) and brain levels. Neurosurgical patients undergoing intracranial surgery or endovascular procedures were given ascending doses of oral DM prior to and 24 hours after surgery. Serum, CSF, and brain levels of DM and its active metabolite, dextrorphan, were measured. One hundred eighty-one patients received a total of 212 courses of DM treatment in dose ranges of 0.8 to 9.64 mg/kg. Serum DM levels correlated highly with CSF and brain DM levels. Brain levels were 68-fold higher than serum levels, whereas CSF levels were fourfold lower than serum levels. The maximum DM levels attained were 1514 ng/ml (serum) 118 ng/ml (CSF), and 92,700 ng/g (brain). The maximum dextrorphan levels were 501 ng/ml (serum), 167 ng/ml (CSF), and 6840 ng/g (brain). In 11 patients, brain and plasma levels of DM were comparable to levels that have been shown to be neuroprotective in animal studies. Frequent side effects occurring at neuroprotective levels of DM included nystagmus (64%), nausea and vomiting (27%) distorted vision (27%), feeling "drunk" (27%), ataxia (27%), and dizziness (27%). All symptoms were reversible and no patient suffered severe adverse reactions. This study demonstrates that potentially neuroprotective doses of DM can be administered safely to neurosurgical patients. Brain and CSF levels of DM can be estimated from serum levels of the drug. Side effects, even at the highest levels, proved to be tolerable and reversible. Administration of DM to patients at risk for cerebral injury should be further explored.
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PMID:Dose escalation safety and tolerance study of the N-methyl-D-aspartate antagonist dextromethorphan in neurosurgery patients. 862 62