Pukkala E, Aspholm R, Auvinen A, Eliasch H, Gundestrup M, Haldorsen T, Hammar N, Hrafnkelsson J, Kyyrönen P, Linnersjö A, Rafnsson V, Storm H, Tveten U. Cancer incidence among 10,211 airline pilots: a Nordic study. Aviat Space Environ Med 2003; 74:699–706. Background: Commercial airline pilots are exposed to cosmic radiation and other potentially carcinogenic elements during work and leisure activities. Hypothesis: Work-related factors affect cancer pattern of the pilots. Methods: A cohort of 10,051 male and 160 female airline pilots from Denmark, Finland, Iceland, Norway, and Sweden was followed for cancer incidence through the national cancer registries. There were 177,000 person-years at follow-up, 51,000 of them accumulated after 20 yr since the time of first employment. Standardized incidence ratios (SIRs) were defined as ratios of observed over expected numbers of cases based on national cancer incidence rates. Dose-response analyses were done with Poisson regression method. Results: Among male pilots, there were 466 cases of cancer diagnosed vs. 456 expected. The only significantly increased SIRs concerned skin cancer: melanoma 2.3 (95% CI 1.7–3.0), squamous cell cancer 2.1 (1.7–2.8), and basal cell carcinoma 2.5 (1.9–3.2). The relative risk of skin cancers increased with the time since first employment, the number of flight hours, and the estimated radiation dose. There was an increase in the relative risk of prostate cancer with increasing number of flight hours in long-distance aircraft (p trend 0.01). No increased incidence was found for acute myeloid leukemia or brain cancer which were of interest a priori based on earlier studies. Conclusions: This large study, based on reliable cancer incidence data, showed an increased incidence of skin cancer. It did not indicate a marked increase in cancer risk attributable to cosmic radiation although some influence of cosmic radiation on skin cancer cannot be entirely excluded.

Feng L-N, Chen W-X, Cong R, Gou L. Therapeutic effects of eustachian tube surfactant in boratitis media in guinea pigs. Aviat Space Environ Med 2003; 74:707–10. Background: Previous research has shown that the eustachian tube (ET) in animals and humans is lined with a substance that lowers surface tension and thus facilitates the opening of the eustachian tube and aeration of the middle ear. The aims of the present study were to observe the role of eustachian tube surfactant (ETS) on the opening of the ET and to explore the therapeutic effect of natural and artificial ETS on barotitis media (BOM). Methods: BOM was successfully established in 50 guinea pigs by simulated ascent in an altitude chamber. Subsets of the affected ears were treated by flushing with natural ETS, artificial ETS, artificial phospholipid, or saline. The effects were evaluated by measuring eustachian tube pressure opening level (POL). Other animals with BOM were treated with artificial ETS on one side and saline in the other, after which the clinical signs were observed. Results: The POL of the saline group remained unchanged. Natural ETS decreased the POL from 11.98 to 6.11 kPa (p < 0.01); artificial ETS reduced the POL from 11.91 to 6.67 kPa (p < 0.01); there was no significant difference between the two treatments. Artificial phospholipid was less effective, decreasing POL from 11.86 to 8.61 kPa (p < 0.05). Clinical observations showed that after 1 wk of treatment with artificial ETS, the congestion in the tympanic membrane was alleviated, the hearing threshold improved, and the effusion in tympanic cavity diminished. Conclusion: Artificial ETS was as effective as natural ETS in facilitating the opening of eustachian tube and had definite therapeutic effects on BOM in this model.

Kumar Y, Chawla A, Tatu U. Heat shock protein 70 as a biomarker of heat stress in a simulated hot cockpit. Aviat Space Environ Med 2003; 74:711–6 Background: Fighter pilots are frequently exposed to high temperatures during high-speed low-level flight. Heat strain can result in temporary impairment of cognitive functions and when severe, loss of consciousness and consequent loss of life and equipment. Induction of stress proteins is a highly conserved stress response mechanism from bacteria to humans. Induced stress protein levels are known to be cytoprotective and have been correlated with stress tolerance. Although many studies on the heat shock response mechanisms have been performed in cell culture and animal model systems, there is very limited information on stress protein induction in human subjects. Hypothesis: Heat shock proteins (Hsp), especially Hsp70, may be induced in human subjects exposed to high temperatures in a hot cockpit designed to simulate heat stress experienced in low flying sorties. Methods: Six healthy volunteers were subjected to heat stress at 55°C in a high temperature cockpit simulator for a period of 1 h at 30% humidity. Physiological parameters such as oral and skin temperatures, heart rate, and sweat rate were monitored regularly during this time. The level of Hsp70 in leukocytes was examined before and after the heat exposure in each subject. Conclusions: Hsp70 was found to be significantly induced in all the six subjects exposed to heat stress. The level of induced Hsp70 appears to correlate with other strain indicators such as accumulative circulatory strain and Craig’s modified index. The usefulness of Hsp70 as a molecular marker of heat stress in humans is discussed.

Schlegel TT, Wood SJ, Brown TE, Harm DL, Rupert AH. Effect of 30-min +3 Gz centrifugation on vestibular and autonomic cardiovascular function. Aviat Space Environ Med 2003; 74:717–24. Introduction: Repeated exposure to increased +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, it is not known whether such enhancements might also result from a single, more prolonged exposure to increased +Gz. Our study was designed to investigate whether baroreflex function and orthostatic tolerance are acutely improved by a single prolonged exposure to +3 Gz, and moreover, whether changes in autonomic cardiovascular function resulting from exposure to increased +Gz are correlated with changes in otolith function. Methods: We exposed 15 healthy human subjects to +3 Gz centrifugation for up to 30 min or until symptoms of incipient G-induced loss of consciousness (G-LOC) ensued. Tests of autonomic cardiovascular function both before and after centrifugation included: 1) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; 2) carotid-cardiac baroreflex tests; 3) Valsalva tests; and 4) 30-min head-up tilt tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counterrolling and dynamic posturography. Results: Of the 15 subjects who underwent prolonged +3 Gz, 4 were intolerant to 30 min of head-up tilt before centrifugation but became tolerant to such tilt after centrifugation. The Valsalva-related baroreflex as well as a measure of the carotid-cardiac baroreflex were also enhanced after centrifugation. No significant vestibular-autonomic relationships were detected beyond a vestibular-cerebrovascular interaction reported earlier in a subset of seven participants. Conclusions: A single prolonged exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance.

Berry NM, Rickards CA, Newman DG. The effect of caffeine on the cardiovascular responses to head-up tilt. Aviat Space Environ Med 2003; 74:725–30. Background: Both caffeine and orthostasis have known cardiovascular effects. The possible interaction between these factors remains unknown. This study aimed to determine the effect of caffeine consumption on cardiovascular responses to head-up tilt. Methods: Sixteen subjects underwent three +75° head-up tilts: i) control, ii) acute, after a dose of 5 mg · kg⁻¹ body mass of caffeine or placebo, and iii) chronic, following 7 d of caffeine or placebo consumption at a daily dose of 5 mg · kg⁻¹ body mass. Heart rate (HR), systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were measured using a Portapres™ BP monitor. Results: The overall pattern of heart rate (HR) response in both caffeine and placebo groups showed a significant increase in HR after tilting for each tilt. Acute caffeine consumption significantly decreased resting HR (p < 0.05). After chronic consumption, resting HR was no longer significantly different. In the control condition, the overall pattern of response to tilt for SBP, DBP, and MAP showed no significant differences in either group. An acute dose of caffeine caused a significant fall (p < 0.05) in all BP variables in response to tilt. This effect was also seen after chronic caffeine consumption in SBP and MAP, but not in DBP. Conclusions: The results of this study indicate that both acute and chronic consumption of caffeine can lead to impaired cardiovascular function after exposure to an orthostatic challenge. This impaired function, reflected in a decreased resting HR and an inability to maintain MAP, is potentially due to impaired baroreflex function.

Cooke WH, Carter JR, Kuusala TA. Muscle sympathetic nerve activation during the Valsalva maneuver: interpretive and analytical caveats. Aviat Space Environ Med 2003; 74:731–737. Introduction: We investigated the relationship between arterial pressure and muscle sympathetic nerve activity (MSNA) to test the hypothesis that the Valsalva maneuver may be used to estimate magnitudes of sympathetic baroreflex activation. Methods: We recorded the ECG, beat-by-beat arterial pressure, and MSNA in 33 subjects (25 men and 8 women, aged 18–25 yr) who performed three Valsalva maneuvers at 40 mmHg expiratory pressure for 15 s. Valsalva phases were identified and the magnitude of pressure changes were correlated with MSNA. Arterial pressure-MSNA relations were probed further with beat-by-beat linear regression analysis after subjects had been separated into responders (n = 20) and non-responders (n = 13) (> or < 10 mmHg decrease in diastolic pressure, respectively). Results: We detected no significant correlations among the magnitudes of either systolic or diastolic pressure reductions and total MSNA. Slopes relating MSNA to beat-by-beat diastolic pressure decreases were greater (p = 0.01) for responders (−3.4 bursts · min⁻¹ · mmHg⁻¹) than non-responders (0.8 bursts · min⁻¹ · mmHg⁻¹), but total MSNA during straining was not different between the two groups. With both groups combined, total MSNA during phase II and III was positively correlated to both systolic (r = 0.41) and diastolic (r = 0.57) pressure during phase IV. Conclusions: Sympathetic activation during the Valsalva maneuver does not necessarily reflect arterial baroreflex mechanisms alone. Phase IV increases of arterial pressure correlate positively to MSNA during phase II and III, and therefore gross estimations of sympathetic neural activation are possible through examination of terminal arterial pressure elevations after release from strain.

Paul MA, McCarthy AE, Gibson N, Kenny G, Cook T, Gray G. The impact of Malarone® and primaquine on psychomotor performance. Aviat Space Environ Med 2003; 74:738–45. Introduction: Recent evidence has established the effectiveness of Malarone® and primaquine for chemoprophylaxis against Plasmodium falciparum malaria. Both have the advantage of providing causal prophylaxis and therefore require continued dosing for only 1 wk after departure from a malaria endemic area. Canadian Forces aircrews are often placed in situations that put them at risk for malaria infection but the safety of these drugs for use in aircrew has not been ascertained. This study was undertaken to determine whether or not Malarone or primaquine impact psychomotor performance. Method: Twenty-eight subjects (20 men and 8 women) ranging from 21 to 52 yr of age were assessed for psychomotor performance on 2 psychomotor test batteries at the end of a 7-d dosing protocol for each of placebo, Malarone, and primaquine treatment, in a double-blind crossover design with counter-balanced treatment order. All subjects were also assessed for psychomotor performance once per week during the 3-wk washout intervals. The daily Malarone dose was atovaquone 250 mg/proguanil 100 mg and the daily primaquine dose was 30 mg of base. In order to verify subject compliance with the medication dosing protocol, blood samples were drawn from all subjects at the end of each of the three 7-d loading protocols. All three medications were packaged in identical gelatin capsules for blinding purposes. At each psychomotor test session, all subjects completed a drug side-effect questionnaire, a mood questionnaire, and a sleepiness/fatigue questionnaire. Results: There was no significant impact of Malarone or primaquine on serial reaction time, logical reasoning, serial subtraction, or multitask performance. With respect to drug adverse effects there were no significant main effects or interactions for the documented adverse effects of these medications (abdominal cramps, epigastric distress, nausea, vomiting, anorexia, headache, coughing and dizziness). Conclusions: There was no impact of either Malarone or primaquine on psychomotor performance, mood, sleepiness, or fatigue. The usual adverse effects of these medications were not significantly manifested in our subjects. These findings support the possible use of either Malarone or primaquine in aircrew for malaria chemoprophylaxis.

Lantos P, Fuller N, Bottollier-Depois J-F. Methods for estimating radiation doses received by commercial aircrew. Aviat Space Environ Med 2003; 74:746–52. Introduction: Radiation doses received onboard aircraft are monitored in Europe to protect aircrew in accordance with a European Union directive. The French Aviation Authorities have developed a system called SIEVERT, using calculation codes to monitor effective radiation doses. Methods: For the galactic cosmic ray component, a 3-D world map of effective dose rates is computed using available operational codes. Detailed flight plans are used to ensure sufficient precision. For the solar particle event component, a semi-empirical model called SiGLE has been developed to calculate a time-dependent map of effective dose rates in the course of the event. SiGLE is based on particle transport code results and measurements during solar particle events onboard Concorde airplanes. Results: We present a comparison of the calculated effective radiation dose and measured dose equivalent for various flights onboard Air France aircraft. The agreement is within 15%, which is about the precision of the state-of-the-art dosimetric measurements. Meteorological effects on the dose calculation appear to be negligible. Preliminary results based on solar particle events observed since 1942 with ionization chambers and neutron monitors are given. Conclusions: The present analysis shows that for the galactic cosmic ray component, monthly world maps based on neutron monitor observations are sufficient to ensure a precision of about 20% on the dose estimate for each flight. For the past 40 yr, according to the model SiGLE, none of the solar events has given an effective radiation dose larger than 1 mSv for flights on the most exposed routes.

Perez SA, Charles JB, Fortner GW, Hurst V IV, Meck JV. Cardiovascular effects of anti-G suit and cooling garment during space shuttle re-entry and landing. Aviat Space Environ Med 2003; 74:753–757. Background: Many cardiovascular changes associated with spaceflight reduce the ability of the cardiovascular system to oppose gravity on return to Earth, leaving astronauts susceptible to orthostatic hypotension during re-entry and landing. Consequently, an anti-G suit was developed to protect arterial pressure during re-entry. A liquid cooling garment (LCG) was then needed to alleviate the thermal stress resulting from use of the launch and entry suit. Methods: We studied 34 astronauts on 22 flights (4–16 d). Subjects were studied 10 d before launch and on landing day. Preflight, crewmembers were suited with their anti-G suits set to the intended inflation for re-entry. Three consecutive measurements of heart rate and arterial pressure were obtained while seated and then again while standing. Three subjects who inflated the anti-G suits also donned the LCG for landing. Arterial pressure and heart rate were measured every 5 min during the de-orbit maneuver, through maximum G-loading (max-G) and touch down (TD). After TD, crewmembers again initiated three seated measurements followed by three standing measurements. Results: Astronauts with inflated anti-G suits had higher arterial pressure than those who did not have inflated anti-G suits during re-entry and landing (133.1 ± 2.5/76.1 ± 2.1 vs. 128.3 ± 4.2/79.3 ± 2.9, de-orbit; 157.3 ± 4.5/102.1 ± 3.6 vs. 145.2 ± 10.5/95.7 ± 5.5, max-G; 159.6 ± 3.9/103.7 ± 3.3 vs. 134.1 ± 5.1/85.7 ± 3.1, TD). In the group with inflated anti-G suits, those who also wore the LCG exhibited significantly lower heart rates than those who did not (75.7 ± 11.5 vs. 86.5 ± 6.2, de-orbit; 79.5 ± 24.8 vs. 112.1 ± 8.7, max-G; 84.7 ± 8.0 vs. 110.5 ± 7.9, TD). Conclusions: The anti-G suit is effective in supporting arterial pressure. The addition of the LCG lowers heart rate during re-entry.

Kraemer WJ, Armstrong LE, Watson G. The effects of exertional heatstroke and exercise-heat acclimation on plasma β-endorphin concentrations. Aviat Space Environ Med 2003; 74:758–62. Introduction: It has been suggested that a proopiomelanocortin peptide β-endorphin may play an important role in temperature regulation and therefore have specific heat stroke response patterns. Methods: The purpose of this study was to examine the response patterns of plasma β-endorphin at baseline, during a 7-d exercise-heat acclimation period (HA; 90 min · d⁻¹, 40°C), and during a 6-h exercise-heat tolerance test (HTT; 6 h, 40°C) performed before and after HA. Subjects were nine previously diagnosed heatstroke patients (P) and eight matched controls (C). No differences between the two groups were observed at rest, prior to HTT. Results: Plasma β-endorphin concentration in P significantly increased above resting values at 2, 4, and 6 h of HTT and were significantly greater than C responses. During HA tests, a significantly higher β-endorphin concentration was observed in P before exercise on day 1 and day 7, but not on day 4. A significant increase occurred after exercise in both groups, on all days of HA; no differences were observed between the groups on days 4 and 7. Discussion: These results demonstrate that the opioid peptide responses in individuals with recent exertional heatstroke were greater than control subjects during the initial 6-h HTT. Decreased physical training among P may have contributed to these results. However, 7 d of HA abolished these between-group differences by reducing the magnitude of β-endorphin responses in P, indicative of an adaptation of pituitary function.

Fitzpatrick DT, Conkin J. Improved pulmonary function in working divers breathing nitrox at shallow depths. Aviat Space Environ Med 2003; 74:763–67. Introduction: There is limited data about the long-term pulmonary effects of nitrox use in divers at shallow depths. This study examined changes in pulmonary function in a cohort of working divers breathing a 46% oxygen enriched mixture while diving at depths less than 12 m. Methods: A total of 43 working divers from the Neutral Buoyancy Laboratory (NBL), NASA-Johnson Space Center completed a questionnaire providing information on diving history prior to NBL employment, diving history outside the NBL since employment, and smoking history. Cumulative dive hours were obtained from the NBL dive-time database. Medical records were reviewed to obtain the diver’s height, weight, and pulmonary function measurements from initial pre-dive, first year and third year annual medical examinations. Results: The initial forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁) were greater than predicted, 104% and 102%, respectively. After 3 yr of diving at the NBL, both the FVC and FEV₁ showed a significant (p < 0.01) increase of 6.3% and 5.5%, respectively. There were no significant changes in peak expiratory flow (PEF), forced mid-expiratory flow rate (FEF_25–75%), and forced expiratory flow rates at 25%, 50%, and 75% of FVC expired (FEF_25%, FEF_50%, FEF_75%). Cumulative NBL dive hours was the only contributing variable found to be significantly associated with both FVC and FEV₁ at 1 and 3 yr. Conclusions: NBL divers initially belong to a select group with larger than predicted lung volumes. Regular diving with nitrox at shallow depths over a 3-yr period did not impair pulmonary function. Improvements in FVC and FEV₁ were primarily due to a training effect.

Knapik JJ, Craig SC, Hauret KG, Jones BH. Risk factors for injuries during military parachuting. Aviat Space Environ Med 2003; 74:768–74. Introduction: Parachuting is an activity performed by a variety of occupational groups including the military, firefighters (smoke jumpers), and rescue groups. Methods: This paper systematically reviewed the literature on injury risk factors for soldiers performing static line parachuting from military aircraft. Jump-related injuries were defined as those occurring from the time the soldier exited the aircraft until he or she released their parachute harness on the ground. Results and Discussion: Despite methodological differences, where two or more studies examined a particular risk factor, results were generally similar. Higher injury risk was associated with higher wind speed, night jumps, jumps from airplanes (vs. balloons and helicopters), jumps wearing additional equipment, jumps without ankle braces, uneven terrain on the drop zone, and female gender. Risk factors identified in only single studies included a greater number of soldiers exiting the aircraft, winds from the rear of the aircraft, simultaneous exits from doors on opposite sides of the aircraft, smaller parachute canopies, higher ambient air temperatures, and airborne refresher courses (vs. introductory courses). Further studies are needed which use a multivariate approach to evaluate the relative impact of the various risk factors and their interactions. Conclusions: This paper identified a number of risk factors relevant to all parachutists (e.g., wind speed, female gender) and some relevant primarily to the military and other tactical parachutists such as smoke jumpers (e.g., equipment weight). Knowledge of these risk factors can assist parachutists and those that train them in their risk analysis.

Akin A, Canakci Z, Sen Z, Tore HF. Chiari-I malformation in two fighter pilots. Aviat Space Environ Med 2003; 74:775–8.This report describes two cases of Chiari Malformation Type I (Chiari-I) in fighter pilots of the Turkish Air Force. Chiari-I is a congenital malformation characterized by herniation of cerebellar tonsils through the foramen magnum. Patients have symptoms and signs related to dysfunction of the brainstem, spinal cord, and cerebellum. They generally are symptomatic in the earlier years of life. However, asymptomatic cases can eventually become symptomatic in later years. Symptoms can be provoked by increasing intracranial pressure (Valsalva or straining). We report on two pilots with Chiari-I malformation who had no symptoms or signs in their daily activities. Furthermore, these pilots had successfully completed physiological training, including centrifuge training, without any symptoms. However, they suffered from headache, neck spasms, and/or disequilibrium under +Gz during flight training sorties. The clinical presentation, diagnosis, treatment, possibility of acquired cases, and aeromedical disposition of Chiari malformations are discussed.

Temme LA, Rupert A. The economic context for the development of “blind flight.” Aviat Space Environ Med 2003; 74:779–84.On 24 September 1929, at Mitchel Field, Long Island, NY, Jimmy Doolittle performed the first so-called “blind flight.” He executed a flight plan and landed using only cockpit instruments, a feat that culminated a research program supported by the Daniel Guggenheim Fund for the Promotion of Aeronautics. Contemporary aviation medicine, with its understanding of the challenges of spatial (dis)orientation, has a special understanding and appreciation of the complex human performance, medical and technical problems that had to be overcome to make instrument flight possible. It is likely that the problems would not have been solved unless a socioeconomic context provoked a sufficient motivation to address them. This paper outlines some of the economic factors that motivated the research and development necessary for instrument flight. These factors were the direct consequence of the sudden, huge explosion of the aviation industry caused by World War I, and with the Armistice, the equally sudden loss of the industry’s primary customer, the military. Finding a civilian role for aviation awaited the development of air mail, which, in turn, depended on the ability to fly according to a reliable schedule. The need to reliably adhere to a schedule forced the scientific and technological research needed to develop all-weather, blind flight.