advantage in day 8 muscle endurance for PB-treated subjects also was not observed posttreatment, giving additional credibility to the authors’ conclusions and arguing against the clinical significance of both of these findings. The authors’ overall conclusion is that treatment of healthy subjects with PB at oral daily doses of 90 mg for 8 days caused no significant neuromuscular effect.

In summary, two studies of healthy volunteers treated with PB, at doses and for a time comparable to those for some military personnel during the Gulf War, found no evidence of significant, clinical neuromuscular abnormality. One study (Graham and Cook, 1984) of men between the ages of 21 and 35 tested grip strength and perceived exertion, and found no significant PB-related changes.

The second study (Glikson et al., 1991) included more detailed strength testing as well as electrodiagnostic studies, but was limited by the extreme youth of its subjects (18–20-year-old males). Any age-related propensity to develop the symptoms seen in Gulf War veterans, which has been reported, would not be apparent in this study. The follow-up period for both studies was very brief—only 1 to 2 weeks after the initiation of therapy—making it difficult to determine whether abnormalities might occur at a later time. It should also be noted that one set of parameters, the electrodiagnostic tests, were performed on only four treated subjects, limiting the ability to rule out the potential for EMG, nerve conduction velocity, and repetitive strength testing abnormalities, which might have been detected by studying a larger, more diverse group for a longer period of time.

Neurobehavioral and Cognitive Function in Healthy Volunteers

A number of controlled studies have shown subtle neurobehavioral changes in subjects exposed to low doses of PB. Cognitive tests such as visuomotor coordination, dynamic visual acuity, reaction time, digit symbol, critical flicker fusion, and mood have been used to assess the effect of PB on performance. Individual performance on these tests was not significantly affected, although when the data were pooled, visual–motor coordination decreased (Borland et al., 1985). One study showed that in addition, perceptual speed and reaction time were impaired by heat and exercise rather than by PB (Arad et al., 1992b). Four subjects exposed to military doses of PB did not show compromised visual performance when tested for low-contrast acuity with dim illumination, a demanding task used to assess aviators’ visual ability (Wiley et al., 1992). Flight performance was not impaired by four doses of 30 mg PB in subjects tested on the A-4 simulator (Izraeli et al., 1990).

A 1984 study of psychomotor performance by Graham and Cook (1984) evaluated the effect of PB on multiple parameters of performance including psychophysiological indices, psychomotor performance, cognitive function, and other central processing functions. In addition, multiple task performance measurements were included in order to assess whether the drug had any impact on conditions of increased workload, where a subject was required to perform two tasks simultaneously (dual-task performance). Finally, subjective measures of symptoms including fatigue, perceived workload, and depression were applied.

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