Evaluation of treadmill exercise in a lower body negative pressure chamber as a countermeasure for weightlessness-induced bone loss: a bed rest study with identical twins.

UNLABELLED: Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative effects of simulated weightlessness on bone metabolism. This protocol may pave the way to counteracting bone loss during spaceflight and may provide valuable information about normal and abnormal bone physiology here on Earth.

Examination of two methods for statistical analysis of data with magnitude and direction emphasizing vestibular research applications.

When the dependent (or response) variable response variable in an experiment has direction and magnitude, one approach that has been used for statistical analysis involves splitting magnitude and direction and applying univariate statistical techniques to the components. However, such treatment of quantities with direction and magnitude is not justifiable mathematically and can lead to incorrect conclusions about relationships among variables and, as a result, to flawed interpretations. This note discusses a problem with that practice and recommends mathematically correct procedures to be used with dependent variables that have direction and magnitude for 1) computation of mean values, 2) statistical contrasts of and confidence intervals for means, and 3) correlation methods.

Adjuvant breast disease: an evaluation of 100 symptomatic women with breast implants or silicone fluid injections.

We evaluated 100 referred women with breast implants (n = 97) or silicone fluid injections (n = 3) into breasts who developed various symptoms. All reported symptoms occurred at a median latency period of 6 years (range 0-24 years) after implantation or injection of silicone. Commonest symptoms were weakness (95%), fatigability (95%), myalgia (90%), morning stiffness (89%), arthralgia (81%), memory loss (81%), sensory loss (77%), headache (73%) and dry eyes and dry mouth (72%). Laboratory results revealed abnormal levels of serum immunoglobulins or complement in 57% and autoantibodies in 78%. Sural nerve biopsy was abnormal in 80% with the major finding of loss of myelinated fibers in 79%. Biceps muscle biopsy was abnormal in 58% with the major finding of neurogenic atrophy in 27%. Ninety-six patients underwent implant removal; 60% of the patients were found to have one or both implants ruptured with silicone spilled into tissue. At time of removal, a pectoralis major muscle biopsy was taken which was abnormal in 89% with the major finding of neurogenic atrophy in 55%. Biopsy of implant capsule was abnormal in 94% showing foreign body giant cells containing refractile material consistent with silicone in 69% whether or not the elastomer shell was ruptured. Silicone can cause a systemic autoimmune disease with a variety of symptoms probably due to a global activation of the immune system. Since our patients had objective laboratory and histologic findings together with a high rate of mechanical implant failure, further investigations are necessary.

Facilitation of adaptation and acute tolerance to stressful sensory input by doxepin and scopolamine plus amphetamine.

This work characterizes a new methodologic and pharmacologic approach to control terrestrial and space motion sickness (SMS). The experimental design allowed separate evaluation of drug action on susceptibility and adaptability, and used repeated measures to approximate the chronic stressful motion of microgravity. Daily exposure to cross-coupled angular acceleration for 5 consecutive days demonstrated that the efficacy of doxepin and scopolamine plus amphetamine in the prevention of autonomic system dysfunction was not only apparent on the first test day (P < .01), but was also evident in the substantially enhanced resistance developed over the 5-day test period (P < .01) as compared with placebo. This indicates that daily use of these medications does not diminish therapeutic efficacy (tolerance). The efficacy of doxepin was anticipated because it possesses pharmacologic properties similar to those of established anti-motion sickness drugs. Comparable efficacy after doxepin loading for 4 hours, 3 days, or 21 days suggests a mechanism distinct from its antidepressant effects, possibly related to its potent antihistaminergic actions. Use of doxepin has operational significance to the National Aeronautics and Space Administration, in comparison with current preparations of scopolamine plus amphetamine, because of doxepin's minimal impact on cognitive performance, and most importantly, its favorable pharmacokinetic profile, particularly its long half-life.

Human performance and physiological function during a 24-hr exposure to 1% bromotrifluoromethane (Halon 1301).

Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon 1301 (bromotrifluoromethane, CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5% of baseline values. Physiological data were obtained before, during, and after the exposures from clinical chemistry analyses of blood and urine samples, pulmonary function tests, and monitoring of vital signs. Significant change during Halon inhalation was observed for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1% Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

Evidence of temporal lobe activation by discriminative spatial orientation.

The results from this spatial orientation, or cue priming, investigation found that targets presented to the contralateral visual fields differentially activated the temporal zones. For instance, stimulation within the right visual field lead to activation of the left temporal zones, as indexed by the relative prominence of the association negativity, N2. The converse was true for left visual field stimulation. For both visual field stimulation, the N2 component also showed an occipital and parietal distribution. The P300 component, which is presumed to be modulated by medial temporal lobe structures, showed the classic centroparietal distribution. Somewhat surprisingly, differences between the primed (e.g., 'facilitated') and 'normal' conditions for the N2 component appeared restricted to the occipital zones. Here, the significant variable was the N2 peak latency. Hence, the priming cue appears to quicken the maximal development of the N2 processing component, preferentially over the occipital cortex, and this may partially explain the faster reaction times in the 'facilitated' conditions for both visual fields.

Vestibular ataxia following shuttle flights: effects of microgravity on otolith-mediated sensorimotor control of posture.

Orbital spaceflight exposes astronauts to an environment in which gravity is reduced to negligible magnitudes of 10(-3) to 10(-6) G. Upon insertion into earth orbit, the abrupt loss of the constant linear acceleration provided by gravity removes the otolith stimulus for vestibular sensation of vertical orientation constantly present on Earth. Since the central nervous system (CNS) assesses spatial orientation by simultaneously interpreting sensory inputs from the vestibular, visual, and proprioceptive systems, loss of the otolith-mediated vertical reference input results in an incorrect estimation of spatial orientation, which, in turn, causes a degradation in movement control. Over time, however, the CNS adapts to the loss of gravitational signals. Upon return to Earth, the vertical reference provided by gravitational stimulation of the otolith organ reappears. As a result, a period of CNS readaptation must occur upon return to terrestrial environment. Among the physiological changes observed during the postflight CNS readaptation period is a disruption of postural equilibrium control. Using a dynamic posturography system (modified NeuroCom EquiTest), 16 astronauts were tested at 60, 30, and 10 days preflight and retested at 1 to 5 hours, and 8 days postflight. All astronauts tested demonstrated decreased postural stability immediately upon return to Earth. The most dramatic increases in postural sway occurred during those sensory conditions in which both the visual and proprioceptive feedback information used for postural control were altered by the dynamic posturography system, requiring reliance primarily upon vestibular function for control of upright stance. Less marked but statistically significant increases in sway were observed under those conditions in which visual and foot support surface inputs alone were altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness.

This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95% confidence interval [95% CI] = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (> 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95% CI = 0.89-0.95), compared to those with early onset (< or = 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS.

Treatment of motion sickness in parabolic flight with buccal scopolamine.

Treatment of acute motion sickness induced by parabolic flight with a preparation of scopolamine placed in the buccal pouch was investigated. Twenty-one subjects flew aboard a KC-135 aircraft operated by the National Aeronautics and Space Administration (NASA) which performed parabolic maneuvers resulting in periods of 0-g, 1-g, and 1.8-g. Each subject flew once with a tablet containing scopolamine and once with a placebo in a random order, crossover design. Signs and symptoms of motion sickness were systematically recorded during each parabola by an investigator who was blind to the content of the tablet. Compared with flights using placebo, flights with buccal scopolamine resulted in significantly lower scores for nausea (31%-35% reduction) and vomiting (50% reduction in number of parabolas with vomiting). Side effects of the drug during flight were negligible. We conclude that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness.

Control of nausea and autonomic dysfunction with terfenadine, a peripherally acting antihistamine.

Terfenadine (Seldane) was administered to 14 male subjects in a randomized, double-blinded, and crossed-over design to assess the efficacy of this peripherally active antihistamine as an anti-motion sickness drug. Terfenadine possesses practically no central side effects. A Staircase Profile Test was administered 4 h following placebo or a single oral dose of terfenadine (300 mg). The study revealed a statistically significant therapeutic effect from terfenadine (p less than 0.05). This led us to conclude that because the drug does not or only poorly crosses the blood-brain barrier, a selective peripheral antihistamine (H1) action may be sufficient in the control of motion sickness induced through cross-coupled accelerative semicircular canal stimulation using a rotating chair. This finding implies that other peripherally acting agents might be found that possess even greater anti-motion sickness efficacy. The present research raises additional questions regarding current theories on the etiology of motion sickness, its associated autonomic system dysfunction, and the validity of assumptions that effective pharmacological agents must act centrally.

Threshold altitude resulting in decompression sickness.

A review of case reports, hypobaric chamber training data, and experimental evidence indicated that the threshold for incidence of Altitude Decompression Sickness (DCS) was influenced by various factors such as prior denitrogenation, exercise or rest and period of exposure, in addition to individual susceptibility. Fitting these data with appropriate statistical models has the potential for estimating the frequency of occurrence of DCS at various altitudes under different experimental conditions and allows us to examine the influence of various factors on the threshold for DCS. This approach was illustrated by logistic regression analysis on the incidence of DCS below 9,144 m (30,000 ft). Estimations using these regressions showed that under a noprebreathe, 6-h exposure, simulated extravehicular activity profile, the threshold for symptoms occurred at approximately 3,353 m (11,000 ft); while under a no-prebreathe, 2-h exposure profile with knee-bends exercise, the threshold occurred at 7,925 m (26,000 ft). These examples showed that definition of threshold altitude should be qualified by the particular combination of experimental variables under which it was observed.

Lack of effects of astemizole on vestibular ocular reflex, motion sickness, and cognitive performance in man.

Astemizole was orally administered to 20 subjects in a randomized, double-blind design to assess the efficacy of this peripherally active antihistamine as an antimotion sickness drug possessing no central side-effects. Measures of vestibular ocular reflex (VOR) were made to evaluate the agent as a selective vestibular depressant. Following 1 week of orally administered astemizole (30 mg daily), a Staircase Profile Test, a VOR test, and a variety of tests of cognitive performance were administered. These tests revealed no statistically significant effects of astemizole. This leads us to conclude that, although the drug probably reaches the peripheral vestibular apparatus in man by crossing the blood-vestibular barrier, a selective peripheral antihistamine (H1) action is inadequate to control motion sickness induced through cross-coupled accelerative semicircular canal stimulation in a rotating chair.

Reliability of provocative tests of motion sickness susceptibility.

Accurate prediction of space motion sickness is dependent, in part, upon the reliability of terrestrial-based motion sickness susceptibility tests. In the present study, test-retest reliability values were derived from motion sickness susceptibility scores obtained from two successive exposures to each of three tests: 1) Coriolis Sickness Sensitivity Index (CSSI); 2) Staircase Velocity Movement Test (SVMT); and 3) Parabolic Flight Static Chair Test (PSCT). The reliability of the three tests ranged from 0.70 to 0.88. Normalizing values from predictors with skewed distributions improved the reliability. The apparent inconsistency between our finding of high reliability of predictive tests, and previous reports of low correlations between ground-based predictors and space motion sickness may be due to unreliability in assessment of the sickness criterion. Issues of reliability and validity of predictor and criterion measures, and their implications for future development of ground-based predictive tests are discussed in some detail.

Arousal and stability: the effects of five new sympathomimetic drugs suggest a new principle for the prevention of space motion sickness.

Sympathomimetic agents are frequent components in antimotion-sickness drug combinations because of their usefulness in counteracting the sedation caused by stressful motion or resulting from the administration of other antimotion-sickness drugs. The noradrenergic neurochemistry of the brain's arousal-attentional systems prompted us to evaluate the efficacy of five new sympathomimetic drugs and to further define the role of arousal in susceptibility to motion. Subjects were orally administered methamphetamine (20 mg), phenmetrazine (25 mg), phentermine (37.5 mg), methylphenidate (20 mg), or pemoline (75 mg) 2 h prior to taking a Staircase Profile Test. All of the drugs increased resistance to stressful coriolis stimulation by 80-120%. Methylphenidate and pemoline showed fewer side effects. These findings, interpreted in conjunction with the documented inefficacy of most anticholinergic and antihistaminergic drugs tested to date, suggest that sympathomimetic drugs or a generalized state of arousal can inhibit the development of motion sickness.