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Melatonin, a pineal hormone present in the blood of humans and other species, has a distinct diurnal variation in its biosynthesis and, therefore, in its concentration. This variation has suggested the possibility of a regulatory function in day/night dependent physiological processes, such as sleep, and has led scientists to explore the effects of administered melatonin on the modulation of circadian rhythms. For the self-treatment of sleep disorders and other benefits, melatonin usage has been extolled to the extent that 20 million new consumers were added to the U.S. retail market in 1995. Its principal aeromedical application has been in the experimental treatment of jet lag effects. For aircraft passengers, melatonin administration at destination-bedtime appears to improve sleep quality and to decrease the time required to reestablish normal circadian rhythms. For international aircrews, who travel through multiple time zones without time to adapt to new environments, taking melatonin prior to arriving home may further impair already disturbed circadian rhythms. Its use to adjust to shiftwork changes by air traffic controllers, aircraft maintenance workers, and support personnel is even more controversial. Limited studies suggest that giving this hormone to shift workers should be done only under controlled conditions and that taking it at the wrong time may actually impair job performance. Because of its possible interaction with certain medications and the changes in its concentrations observed in some clinical conditions, the practitioner must exercise caution during the medical certification of airmen. The variations in the concentration of melatonin can be effectively determined by radioimmunoassay, high-performance liquid chromatography, and gas chromatography-mass spectroscopy analytical techniques.

A major concern in aviation medicine is the cabin inflight emergency that may result in the diversion of a flight. At the present time there is no convenient way to monitor the incidence of inflight medical emergencies because airline companies are not regularly required to report medical emergencies or resulting diversions. A survey of one major US airline revealed that one out of every one million passengers may be deplaned by an unscheduled landing because of a life-threatening medical emergency. During a two-year FAA survey of US domestic flights there were 2,322 inflight medical emergencies, averaging approximately three per day, which resulted in an annual diversion rate of approximately 9%. In a 1989 study, inflight emergencies among arriving passengers at the Los Angeles International airport were analyzed. During the six-month period of the investigation 0.003% of 8.5 million passengers developed symptoms in flight that required follow-up assistance on the ground, and 10% of these passengers required hospitalization. A survey of the status of inflight medical care aboard domestic US air carriers was undertaken to determine the impact of current changes in the airline industry. Information for the years 1990 to 1993 was obtained from two airlines and two inflight medical care delivery companies, representing a total of nine major US Part 121 air carriers. This sample accounted for approximately 65% of US domestic air carrier activity for the period 1990 to 1993. The information was reviewed to determine which category of inflight medical emergency occurred most frequently and which category accounted for the greatest number of diversions. The trend in the frequency of diversions for medical reasons was also assessed. The impact of inflight medical advice was then evaluated by comparing the number of diversions that resulted in hospitalizations to the numb

Biological specimens from 8 fatal aviation accidents out of 775 fatal aviation accidents analyzed in 1991 and 1992 were found to contain quinine. In one case, the investigators sought to identify the source of quinine found in the pilot. It was suggested that the quinine might have come from the consumption of tonic water. Since no recent use of quinine or tonic water could be found, the investigators asked how long quinine could be detected in a urine specimen. A limited research project was undertaken to provide a preliminary range of the approximate length of time quinine could be detected in urine and blood. Each of 2 male subjects was given a 20 oz. bottle of tonic water, which contained 35 mg of quinine. Quinine was detected using standard laboratory TLC and HPLC methods. Quinine has such diverse applications as a treatment for muscle cramps and malaria, in addition to being an additive in tonic water. Since adverse effects have been identified at plasma concentrations between 10- 15 microgram/mL, no performance effects would be expected from the maximum concentrations of quinine found (0.291 microgram/mL) in this study after the ingestion of one 20 oz. bottle of tonic water. However, based on this study, the possibility of prolonged detection (over 8 days) of quinine should (a) serve as a warning against using this as a sign of recent use of quinine directly or in association with alcohol, and (b) alert the investigators to inquire about disorders or conditions that impair performance, but for which quinine treatment was terminated days before the accident.

A panel of the American Medical Association convened by the Federal Aviation Administration recommended that a computerized test of cognitive function be developed that would detect significant cognitive impairments that might otherwise go unrecognized during a routine physical examination. In response to this need, a computerized test battery, based on current cognitive theory, has been developed that provides a brief screening for disturbances in higher-level cognitive function. This battery is not designed to replace the traditional observational methods used by the physician, but rather to enhance diagnostic sensitivity in areas not currently well covered. The battery operates in a 'step fashion, providing a generalized, non-specific screen at the first level, with two increasingly more specific screens if that level is failed. The output of the battery is a verbal protocol to the examiner presenting a series of rule out recommendations for further diagnostic testing. In this report, the background and composition of this test are described, and the results of three initial validation and sensitivity studies are reported.

Triamterene, a diuretic drug used in combination with other drugs for the treatment of hypertension, was found in the blood and urine of a fatal aircraft accident victim. The extraction and identification of triamterene is difficult. It exhibits poor extraction efficiency using some standard base extraction procedures and the parent drug is unsuitable for analysis using gas chromatography. In this case a thin layer chromatography solvent system and high performance liquid chromatography were used to identify and quantitate triamterene in blood and urine. Triamterene is a strong absorber in the ultraviolet region and has an unusual UV spectrum, which simplifies the identification and quantitation of this substance by High Performance Liquid Chromatography.

To evaluate the effects of orthostatic, attitude, and pharmacologic stresses upon civil aviation-specific performance, a double-blind, randomized, crossover trial of atenolol, 100mg, was designed and executed. Hypertensive mates and females qualifying for the FAA class 3 certificate with mean age of 34 were studied during simulated attitude exposure to 12,500 ft, orthostatic stress, and moderate exercise. Seated Lower body negative pressure to -40 mmHg supplied orthostatic stress simulating +2G vertical acceleration. A total of 160 Lower body negative pressure tests were performed, 80 at ground and 80 at altitude. Beta-blockade caused a modest impairment in orthostatic tolerance. Five of the 80 Lower body negative pressure runs at ground level were marked by intolerance, and all of those responses were in beta-blocked subjects. of the 80 attitude runs, 30 were terminated for intolerance, of which 18 included beta- blockade. These findings had a Chi-square significance value of P < .05. The effect of attitude was significant at P < .01. In a modest exercise protocol (100 watts for 3 minutes) meant to be no more stressful than the exertional requirements of piloting an aircraft during adverse conditions, neither beta- blockade or altitude appeared to Limit performance. Quantitative performance on a computerized cognitive battery clearly demonstrated impaired performance during Lower body negative pressure stress at altitude. The degree of impairment was significant compared to a learning curve response at the P < .001 level. The degree of impairment was similar for placebo treated and beta-blocked subjects.

Civil Aerospace Medical Institute, 1992, PDF, Tech Report, Teague, Steven M., Hordinsky, Jerry R., Civil Aeromedical Institute, United States. Office of Aviation Medicine, Civil Aerospace Medical Institute, United States, Air pilots, Hypertension, Altitude, Physiological aspects, Drug effects, Blood pressure, Atmospheric pressure, Tolerance (Physiology), Performance tests, Heart rate, Hypoxia, Certification, Air pilots--Certification, Hypertension, Atenolol, Altitude, Influence of, Drugs--Physiological effect, Blood pressure, Heart beat, Atmospheric pressure, Performance--Testing, Cerebral anoxia, Hemodynamic monitoring, Vascular resistance, DOT/FAA/AM-92/19, To evaluate the effects of orthostatic, altitude, and pharmacologic stresses upon civil aviation-specific performance, a double-blind, randomized, crossover trial of atenolol, 100mg, was designed and executed. Hypertensive males are females qualifying for the FAA class 3 certificate with mean age of 34 were studied during simulated altitude exposure to 12,500 ft, orthostatic stress, and moderate exercise. Seated lower body negative pressure to -4C mmHg supplied orthostatic stress simulating +2G vertical acceleration. A total of 160 lower body negative pressure tests were performed, 80 at ground and 80 at altitude. Beta-blockade caused a modest impairment in orthostatic tolerance., Five of the 80 lower body negative pressure runs at ground level were marked by intolerance, and all of those responses were in beta-blocked subjects. Of the 80 altitude runs, 30 were terminated for intolerance, of which, ch 18 included beta-blockade. These findings had a Chi-square significance value of P < .05. The effect of altitude was significant at P < .01. In a modest exercise protocol (100 watts for 3 minutes) meant to be no more stressful. than the exertional requirements of piloting an aircraft during adverse conditions, neither beta-blockade or altitude appeared to limit performance.Quantitative performance on a computerized cognitive battery clearly demonstrated impaired performance during lower body negative pressure stress at altitude. The degree of impairment was significant compared to a learning curve response at the P < .001 level. The degree of impairment was similar for placebo treated and betablocked subjects., Monitoring of mean arterial pressure, heart rate, and stroke volume was necessary for quantitative analysis of hemodynamic responses to these stressors. These parameters demonstrated progressive decrements in systemic vascular resistance in intolerant subjects, implicating a defective peripheral autonomic nervous system response. Moreover, monitoring of systemic vascular resistance, blood pressure, and transcranial Doppler middle cerebral artery flow velocities allowed prediction of impending cognitive and hemodynamic collapse. These data implicate the synergistic deleterious effects of beta-blockade and altitude in the potentiation of intolerance to orthostatic stress. These findings may have most revelance to the personnel of unpressurized aircraft who are being treated with beta-blocking drugs for hypertension. No common clinical parameter predicts subsequent intolerance. It appears that only formal stress testing will uncover orthostatic-prone individuals., 1199

Civil Aerospace Medical Institute, 1994, PDF, Tech Report, White, Vicky L., Canfield, Dennis V., Hordinsky, Jerry R., Civil Aeromedical Institute, United States. Office of Aviation Medicine, United States, Air transportation crashes, Fatalities, Drug use, Urinalysis, Blood analysis, Air pilots, Laboratory studies, Aircraft accidents, Air pilots, Mineral waters, Quinine--Testing, Urine--Analysis, Blood--Analysis, DOT/FAA/AM-94/16, Biological specimens from 8 fatal aviation accidents out of 775 fatal aviation accidents analyzed in 1991 and 1992 were found to contain quinine. In one case, the investigators sought to identify the source of quinine found in the pilot. It was suggested that the quinine might have come from the consumption of tonic water. Since no recent use of quinine or tonic water could be found, the investigators asked how long quinine could be detected in a urine specimen., A limited research project was undertaken to provide a preliminary range of the approximate length of time quinine could be detected in urine and blood. Each of 2 male subjects was given a 20 oz. bottle of tonic water, which contained 35 mg of quinine. Quinine was detected using standard laboratory TLC and HPLC methods. Quinine has such diverse applications as a treatment for muscle cramps and malaria, in addition to being an additive in tonic water. Since adverse effects have been identified at plasma concentrations between 10 15 ~g/mL, no performance effects would be expected from the maximum concentrations of quinine found (0.291 ~g/mL) in this study after the ingestion of one 20 oz. bottle of tonic water., However, based on this study, the possibility of prolonged detection (over 8 days) of quinine should (a) serve as a warning against using this as a sign of recent use of quinine directly or in association with alcohol, and (b) alert the investigators to inquire about disorders or conditions that might impair performance, but for which quinine treatment was terminated days before the accident., 1199

Civil Aerospace Medical Institute, 1992, PDF, Tech Report, White, Vicky, Canfield, Dennis V., Hordinsky, Jerry R., Civil Aeromedical Institute, United States. Office of Aviation Medicine, Civil Aerospace Medical Institute, United States, Air transportation crashes, Air pilots, Drug effects, Hypertension, Blood analysis, Urinalysis, Drug tests, Gas chromatography, Aircraft accidents, Air pilots, Drugs--Physiological effect, Triamterene, Hypertension, Blood--Analysis, Urine--Analysis, Gas chromatography, DOT/FAA/AM-92/23, Triamterene, a diuretic drug used in combination with other drugs for the treatment of hypertension, was found in the blood and urine of a fatal aircraft accident victim. The extraction and identification of triamterene is difficult. It exhibits poor extraction efficiency using some standard base extraction procedures and the parent drug is unsuitable for analysis using gas chromatography. In this case a thin layer chromatography solvent system and high performance liquid chromatography were used to identify and quantitate triamterene in blood and urine. Triamterene is a strong absorber in the ultraviolet region and has an unusual UV spectrum, which simplifies the identification and quantitation of this substance by High Performance Liquid Chromatography, 1199

Civil Aerospace Medical Institute, 1992, PDF, Tech Report, O'Donnell, Robert D., Hordinsky, Jerry R., Madakasira, Sudahar, Moise, Samuel, Warner, Debra, Civil Aeromedical Institute, United States. Office of Aviation Medicine, Civil Aerospace Medical Institute, United States, Neurology, Medical examinations and tests, Psychiatry, Mental condition, Air pilots, Performance tests, Air pilots, Neuropsychological tests--Technological innovations, Mental health, DOT/FAA/AM-92/11, A panel of the American Medical Association convened by the Federal Aviation Administration recommended that a computerized test of cognitive function be developed that would detect significant cognitive impairments that might otherwise go unrecognized during a routine physical examination. In response to this need, a computerized test battery, based on current cognitive theory, has been developed that provides a brief screening for disturbances in higher-level cognitive function. This battery is not designed to replace the traditional observational methods used by the physician, but rather to enhance diagnostic sensitivity in areas not currently well covered., The battery operates in a “step” fashion, providing a generalized, non-specific screen at the first level, with two increasingly more specific screens if that level is failed. The output of the battery is a verbal protocol to the examiner presenting a series of “rule out” recommendations for further diagnostic testing. In this report, the background and composition of this test are described, and the results of three initial validation and sensitivity studies are reported. The present test development suggests the utility of transferring previously expensive and more complex diagnostic approaches to a computerized testing and decision process. This development of an automated approach to cognitive function testing was one of three sponsored by the FAA Office of Aerospace Medicine during 1987 - 1990., 1199