Author	Sample Size	Sample/Study Characteristics	Dose	Findings
Wenger, 1993	7	Healthy male soldiers age 22±2.8 Placebo controlled partial-double-blind crossover with 7 d phases after heat acclimation	30 mg q8 hr for 19 doses, or placebo	PB caused a modest increase in whole-body sweating and reduced skin temperature on the chest during exercise by 0.5-0.9° C. Trend toward increased rectal temperature "Near lack of adverse effects"
Wenger, 1992; Wenger, 1992	6	Healthy male soldiers, age 25.6�9.6: test outcomes with heat, exercise, and hypohydration	PB 30 mg tab or placebo	"PB had only minor effects on tolerance to moderate exercise-heat stress and did not aggravate the strain of hypohydration" Rectal temperature: PB reduced rise in Tre but significant only during hypohydration Skin temperature on chest: decreased with exercise at 20% rh, more with PB, significant only in condition 2 Skin temperature on upper arm: no difference? Skin temperature on calf: No difference Heart rate: lowered 3 beats/min (p = .004) PB decreased expansion of plasma volume that occurred during heat exposure: significant only at 75% rh
Roberts, 1994	7	Healthy male		No change in thermoregulation during exercise in cold air
Roach, 1991	30	10 nonsmokers, 10 smokers, and 10 mild asthmaticsDouble-blind placebo-controlled crossover with PB or placebo before bronchoprovocation	30 mg q8 hr	No effect of PB on nonspecific bronchial hyperreactivity in normals, smokers, or asthmatics

Author	Sample Size	Sample/Study Characteristics	Dose	Findings
Ram, 1991	25	12 healthy and 13 asthmatic	60 mg once30 mg	Statistically but not physiologically significant decrease in FEV1 at rest (p < .015) and with exercise (p < .05), strongly correlated to degree of AChE inhibitor (p < .00001) AChE inhibition: 28% with 60 mg; 23% with 30 mgPulse: significantly reduced (p < .005) Respiratory function: no change Cannot preclude more vulnerable subpopulation of asthmatics
Arad, 1992	8	Hypertensive patients on beta-blockers Randomized double-blind crossover PB or placebo for 2 days	30 mg tid for 2 days	No clinical adverse effects of PB No significant effect on heart rate, plasma catecholamine level, or resting blood pressure Lower diastolic blood pressure with PB with exercise (average decrease 5 mm Hg versus placebo, p < .01)
Epstein, 1990	8	Male heat-acclimatized volunteers, age 23.5±1.1 Randomized double-blind crossover with subjects exposed to 170 min of exercise heat stress (relative humidity 60%, Tdb 33° C)	30 mg q8 hr for 4 doses versus placebo	Average 33% whole blood cholinesterase inhibition 4 hr after last tablet Higher non-evaporative heat exchange with PB (p < .03) No difference in heart rate, rectal temperature, heat storage, and sweat rate with PB versus placebo
Levine, 1991	10	Healthy male soldiers Counterbalanced drug and control: 2 days tested with drug, 2 with placebo Not stated to be blinded	PB 30 mg tab once, or placebo; test days separated by = 48 hr	No change in pulmonary function tests with PB: FEV1, FVC, maximum voluntary ventilation in 15 seconds, carbon dioxide sensitivity, or maximum inspiratory or expiratory flow rates
Levine, 1991	7	Healthy male soldiers Counterbalanced drug and control: 2 days tested with drug, 2 with placebo Not stated to be blinded	PB 30 mg tab once or placebo; test days separated by = 48 hr	No significant change in skeletal muscle strength (peak hand-grip strength and 60% peak hand-grip endurance time, peak torque for leg extension), and muscle tissue damage by serum enzymes

Author	Sample Size	Sample/Study Characteristics	Dose	Findings
Kolka, 1991		Placebo-controlled crossover	PB 30 mg po tid	PB lowers esophageal temperature and HR in hot environment; HR in warm environment
	5	Healthy males age 20�2 tested at rest, 2 hr after PB, and 2 hr p seventh PB tab in hot environment		Reduced resting esophageal temperature and heart rate with PB (p <.05) no change in arterial blood pressure, forearm blood flow and forearm skin blood flow; *74 hr data presented for a mean of only 3 of the 5 subjects because PB was discontinued in 2 due to high red blood cell AChE inhibition
	4	Healthy males age 19.4±0.5 tested (a) control at sea level (b) control at 10,000 feet; (c) 2 hr after first PB at 10,000 feet; (d) 26 hr after first and 2 hr after fourth PB tab; (e) sea level 2 hr after tenth tab Tested in warm environment at sea level and 10,000 feet		Lower esophageal temperature (trend only) at sea level HR lower at sea level 74 hr after PB
Stephenson, 1989;	5	Healthy adult males	PB 30 mg po or no drug, 150 min before	40% decrease red blood cell AChE (329%�7)
Stephenson, 1990;Kolka, 1990	4			PB decreased skin blood flow; PB decreased heart rate at rest and in exercise Esophageal temperature: increased with exercise only with PB 8-site mean skin temperature Forearm blood flow (venous occlusion plethysmography): no change Cutaneous perfusion (laser doppler velocimetry): reduced 37% after PB (p = .05) with higher temperature threshold for initiation of cutaneous perfusion of PB (p = .01) Slope of LDV: esophageal temperature was reduced 35% with PB (p = 0.22) Metabolic rate (indirect calorimetry)

Author	Sample Size	Sample/Study Characteristics	Dose	Findings
Arad, 1992	8	Healthy males	30 mg q8 hr for 4 doses	No significant effect of PB, protective gear, or interactions on performance of vertical addition, reaction time, or perceptual speed
Forster, 1994	5	Healthy male members of human centrifuge acceleration pattern; age 26±3; weight 80±4 kg	30 mg q8 hr or placebo	PB level range: 6-31 ng/ml AChE inhibitor range: 12-45% No significant differences in ratings for fatigue, symptoms, and work effort; grip strength; tapping task Sternberg memory search; critical tracking, Dual Sternberg, and tracking pulmonary function tests; Acceleration tolerance; heart rate, QT interval, PR interval
Borland, 1985	4	Healthy male 19-27 years Crossover; double-blind crossover	PB 30 mg q8 hr for 3 days or placebo	"Minimal if any effects" Increased mean critical flicker fusion; impaired visuomotor coordination performance; no changes in mood, mean choice reaction time; grating contrast sensitivity; macular thresholds, digit symbol substitution, symbol copying; quantitative kinetic perimetry, EEG during mental arithmetic
Wiley, 1992	4	Healthy aviators	PB 30 mg q8 hr for 3 days after baseline measurements	Visual ability "not significantly compromised"; refractive error and pupil diameter significantly different, but no change in lateral phoria, fusional vergence, accommodative amplitude with PB

Author	Sample Size	Sample/Study Characteristics	Dose	Findings
Izraeli, 1990	10	Pilots experienced in actual and simulated A-4 flights Double-blind placebo-controlled crossover	PB 30 mg q8 hr	No decrement in performance under treatment with PB
Brooks, 1992	24	A-10 pilots Crossover counterbalanced double-blind trial of performance with PB versus placebo	PB 30 mg tid versus placebo	No operationally significant effects of PB. No clear interference of PB with performance

Author	Sample Size	Sample/Study Characteristics	Dose	Findings
Sharabi, Danon, et al., 1991	213	Male Israeli soldiers 18-22, retrospective cohort	30 mg q8 hr	No correlation between AChE inhibition and type or severity of symptoms Malaise: 53% Fatigue, numbness: 37% Headache: 29% Dizziness, imbalance: 19% Moodiness: 18% Restlessness: 18% Heavy extremities: 10% Excessive sweating: 9% Altered mood: 8% Sense of fear: 6% GI: Dry mouth: 71% Nausea: 22% Abdominal pain: 20% Lack of appetite: 14% Diarrhea: 6% Other: Hot flushes: 20% Rhinorrhea: 10% Rapid heart beats: 8% Frequent urination: 11%
Keeler, 1991	"Approximately 30"	Retrospective survey of proxy recollection by medical support personnel involved with 41,650 soldiers in PGW	30 mg q8 hr	GI symptoms: 50% Urinary: 5�30% Headache, rhinorrhea, diaphoresis, tingling of extremities: < 5% Need for medical visit: 1% Discontinuation on medical advice: < 0.1%

Author	Sample Size	Sample/Study Characteristics	Dose	Findings
Kennedy, 1991	1	Case report of PGW medical officer (letter to editor)	30 mg q8 hr	Esophageal spasm with chest pain and trouble swallowing Reports of others' abdominal and skeletal muscle cramps, increased bowel gas, blurred vision, and one claim of a 36-hour erection
Almog, 1991	9	Observational report of 9 cases of PB overdose	13 to 39 PB tabs	Muscarinic: abdominal cramps, diarrhea, nausea, vomiting, salivation, urinary incontinence (lacrimation and sweating not prominent) Nicotinic symptoms: transient fasciculations and muscle weakness Central symptoms: (not seen: ataxia, confusion, psychosis, respiratory or cardiovascular depression, seizure, coma) No relation between symptoms and AChE inhibition; major symptoms resolved in several hours while cholinesterase returned to normal in 1-2 days