minor gastrointestinal and urinary symptoms than expected. An estimated 1 percent of the soldiers had effects from PB for which they sought medical advice, and less than 0.1 percent had effects that warranted its discontinuation.

On their return from the Gulf War, two women sought counseling about their pregnancies because they realized they had been exposed, during their first trimester, to PB and anthrax vaccine (Sarno et al., 1991). PB has been used in pregnancy without producing fetal anomalies, but Sarno and colleagues (1991) note that there are no controlled studies of PB and reproductive risks in females.

Keeler and colleagues (1991) suggest that the higher proportion of personnel experiencing adverse physiological effects than reported in peacetime evaluations may result from the combined effects of anticipated combat, sleep deprivation, and life in the field. Due to the limitations of the retrospective and uncontrolled nature of the data, Neish and Carter (1991) challenged these conclusions.

Acute poisoning with PB is uncommon, but Almog and colleagues (1991) report on nine cases of self-poisoning in men (n = 6) and women (n = 3) age 17–19 years associated with misuse of PB that was widely distributed as a prophylactic drug during the Gulf War. The doses ranged from 390 to 900 mg, but no CNS toxicity was observed in the nine patients. Mild to moderate cholinergic symptoms developed within several minutes after ingestion and lasted up to 24 hours. Two of the nine patients presented with muscarinic signs such as abdominal cramps, diarrhea, nausea, hypersalivation, vomiting, and urinary incontinence. One patient was observed to have transient nicotinic effects of fasciculations and weakness. The authors concluded that PB intoxication is self-limited and that PB is well tolerated by young adults (Almog et al., 1991). Thus, the various studies of PB exposure provide evidence that PB is not highly toxic, even at high doses or when taken during combat conditions.

Clinical Studies of PB and Neuromuscular Effects

A group of 17 patients with postpoliomyelitis syndrome (PPS) and 10 controls were studied for response to ChE inhibitors (Trojan et al., 1993). Patients with PPS suffer generalized weakness as well as signs and symptoms of muscle weakness thought to be due to neuromuscular junction transmitter defects. Patients responsive to the short-acting anticholinesterase edrophonium were subsequently treated with oral PB at 180 mg daily in divided doses for a period of a month. Side effects included intestinal cramps, diarrhea, muscle cramps, anxiety, blurred vision, and increase in urinary frequency. Using mobility and subjective fatigue as end points, clinical response to PB was measured before treatment and 1 month after treatment. Nine of the seventeen patients reported improvement in fatigue, including reduction in systemic fatigue as well as less muscle fatigability. One patient experienced reversible worsening of symptoms of fatigue. The nine responding patients continued the drug for a mean of 1.2 years despite associated mild gastrointestinal side effects. No other significant side effects were observed.



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