Aims To investigate the effect of monoamine oxidase A inhibition from a single oral dose of linezolid on the pressor response to intravenous (i.v.) tyramine, using positive and negative controls to validate the methodology. Methods This placebo‐controlled, three‐period crossover study was conducted in 12 healthy male volunteers. Each volunteer received either one oral dose of moclobemide (300 mg), linezolid (600 mg), or placebo tablet followed by an i.v. tyramine pressor test until an increase in systolic blood pressure of at least 30 mmHg above baseline occurred. Each study day was separated by a 7‐day washout period. The dose of tyramine required to raise the blood pressure by 30 mmHg (TYR30) was calculated for each oral treatment by linear interpolation between log‐transformed doses of i.v. tyramine. The influence of body mass index (BMI) on TYR30 was also investigated. Results The tyramine sensitivity factor (ratio of the geometric least square mean TYR30 for placebo and active oral treatment) was 1.8 [90% confidence interval (CI) 1.6, 2.0, P < 0.0001] for linezolid and 2.1 (90% CI 1.8, 2.4, P < 0.0001) for the positive control moclobemide. BMI had a statistically significant effect on TYR30. Conclusions There was a significant difference in the pressor response to i.v. tyramine between linezolid and placebo. Moclobemide (positive control) and linezolid have a similar pressor response to i.v. tyramine. The statistically significant effect of BMI on TYR30 underlines the advantage of within‐individual comparisons of treatments in order to reduce variability and provide more accurate treatment estimates.

This study compares the acute and chronic response of brain tissue to injury by equal power density, focused argon (Ar) and carbon dioxide (CO2) laser beams. A cortical incision from 0.2-second laser pulses of 12.5 X 10(3) W/cm2 power density was made in the exposed cortex of 32 rats using either the CO2 or the Ar laser. The brains were examined at intervals from 1/2 hour to 1 month after injury. Histologically, all brain incisions were sharply demarcated hemispheroidal defects with a vaporized center bordered by a zone of coagulation necrosis surrounded by edema. The laser incisions were found to be of equal depth (less than 1 mm). The average cortical surface diameter of the CO2 laser incision was 0.86 mm for a focused beam spot size 0.45 mm in diameter, compared with 0.65 mm with the Ar laser, which had a focused beam spot size 0.15 mm in diameter. In both incisions, some delayed depth effect was observed. A progression of the tissue necrosis by approximately 17% was observed during the first 24 hours after injury. During the first 4 hours after injury, the Evans blue blood-brain barrier defect (EBBD) surrounding the cortical incisions averaged 5.80 mm2 for the CO2 incision and 0.888 mm2 for the Ar incision. In both types of brain incision, the EBBD appeared to resolve by 24 hours after injury. At 1 month after injury, a core of coagulation necrosis surrounded by mild fibrillary gliosis was observed. At the power density and focused beam spot sizes used, there was no significant difference in the overall brain tissue response to Ar and CO2 laser lesions.

Using a CO2 laser, discrete thoracic spinal cord lesions were made in cats anesthetized with ketamine and xylazine (Rompun). Differences in cortical somatosensory evoked potentials (SEP's) produced with high-intensity stimulation (20 times the motor threshold) of each posterior tibial nerve determined for nine different combinations of unilateral spinal cord lesions. The results of these studies show that nerve fibers in the ipsilateral dorsal column, the ipsilateral dorsal spinocerebellar tract, and the contralateral ventrolateral tracts with respect to the side of leg stimulation, contribute to cortical SEP's. A lesion of the dorsal spinocerebellar tract affected only the early waves (less than 30 msec) of the SEP from leg stimulation ipsilateral to the side of the lesion, whereas a solitary lesion of the ventrolateral tract caused changes primarily in the amplitude of later waves (greater than 30 msec) of the SEP produced by contralateral leg stimulation. Lesions involving one-half of the dorsal column caused changes in the amplitude of both the early and late waves produced by stimulation ipsilateral to the side of the lesion. The effects of various combinations of lesions on the cortical SEP's were not additive, which indicates significant interaction between afferent pathways. These findings suggest that high-intensity peripheral nerve stimulation, which activates both C and A fibers, could be used intraoperatively to assess spinal cord function with more accuracy than the current practice of using a stimulus strength of twice the motor threshold. The importance of using anesthetic agents that do not depress cortical activity (which may affect the later components of the SEP) is also emphasized.

Central neurotoxicity produced in rats by daily administration of 300 mg/kg of misonidazole (MISO) 5 times/week for 4-5 weeks (total dose = 6.0 gm/kg) was evaluated weekly wit brain stem auditory evoked potentials (BAEPs). Compared to untreated control rats, all treated rats had a prolongation of the I-IV interpeak latency (p less than 0.005) at a mean of 13.2 +/- 2.7 days at a cumulative dose of approximately 4.0 gm/kg of MISO per rat. In some rats, the I-III and I-II interwave latencies were prolonged and waves III and IV were lost. Control rats did not show any significant alteration in BAEP latency or amplitude. Histopathologic examination of the brain stems of treated rats showed that necrotic lesions were present primarily in the nuclei of the tegmentum of the fourth ventricle, with scattered nuclear involvement in the cerebellar roof nuclei, inferior olive, and nucleus of the spinal tract of the trigeminal nerve. The cerebral cortex appeared to be normal in all treated rats. Changes in BAEPs caused by central neurotoxicity correlated with the histopathologic findings. We conclude that BAEPs are a sensitive method for evaluating MISO central neurotoxicity in the rat model.