of the population may not achieve CW protective red blood cell AChE inhibition levels (>10 percent inhibition) on this standard regimen.

Loewenstein-Lichtenstein and colleagues (1995) presented a case study of an Israeli soldier who suffered from severe symptoms of nausea, insomnia, weight loss, fatigue, and depression while receiving standard doses of PB during the Gulf War as CW pre-exposure prophylaxis. The symptoms resolved some weeks after PB was discontinued. His past medical history was noteworthy for an earlier episode of postanesthesia apnea (succinylcholine used as paralytic agent). The authors analyzed the soldier’s BuChE activity spectrophotometrically and also delineated his (and his family’s) genotype by recombinant expression in Xenopus oocytes. These studies documented the subject to be homozygous for the most common variant allele of BuChE, with enzyme serum activity about one-third that associated with the usual genotype. The authors noted that homozygous carriers of this particular allele comprise about 0.04 percent of people of European ancestry but may be as high as 0.6 percent in certain subsets of this population. They posited that such atypical homozygotes and possibly even heterozygotes could be at risk for severe symptoms from PB due to the relative deficiency of PB-scavenging effective BuChE. They further speculated that anticholinesterase exposure might lead to long-term adverse consequences with symptoms that are not incompatible with those of Gulf War veterans, and that combined exposures to other ChE inhibitors might increase the risk of such outcomes.

In summary, individuals within a healthy population differ widely in their rates of absorption, distribution, elimination (PK), and enzymatic inhibition (PD) related to PB. PK is affected by weight and gender, whereas PD may vary considerably between normal individuals. Genotypic variations of BuChE may cause adverse (conceivably, long term) effects in some populations. Further studies to identify the relationship between such variants and the risk of both acute and chronic health outcomes is warranted (see Chapter 8).

Epidemiologic Studies

A number of clinical and human volunteer studies have investigated a range of potential adverse responses associated with PB exposure. These are described above and essentially indicate minimal toxicity of PB with no irreversible side effects.

Although there have been several descriptive epidemiologic studies of Gulf War veterans, these investigations sought to characterize the nature and frequency of the illnesses reported by returning soldiers and did not examine the association of PB with these illnesses.

There are no analytic epidemiologic studies of the association of PB and adverse health effects in humans. Such studies would optimally have to include both exposed and nonexposed individuals as well as deployed and nondeployed soldiers to control for the environmental conditions associated with combat. A series of reports published by Haley and colleagues attempt to evaluate illnesses in Gulf War veterans (referred to by the authors as Gulf War syndrome) and

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