Search NASASearch

SEARCH · Search NASA

Results for “Randomized Controlled Trial”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3

A phase response curve to single bright light pulses in human subjects

The circadian pacemaker is differentially sensitive to the resetting effects of retinal light exposure, depending upon the circadian phase at which the light exposure occurs. Previously reported human phase response curves (PRCs) to single bright light exposures have employed small sample sizes, and were often based on relatively imprecise estimates of circadian phase and phase resetting. In the present study, 21 healthy, entrained subjects underwent pre- and post-stimulus constant routines (CRs) in dim light (approximately 2-7 lx) with maintained wakefulness in a semi-recumbent posture. The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze (approximately 10 000 lx) and free gaze (approximately 5000-9000 lx) exposures. Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC. Plasma melatonin was used to determine the phase of the onset, offset, and midpoint of the melatonin profiles during the CRs. Phase shifts were calculated as the difference in phase between the pre- and post-stimulus CRs. The resultant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak-to-trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum, phase advances occurred when the light stimulus was centred after the critical phase, and no phase shift occurred at the critical phase. During the subjective day, no prolonged 'dead zone' of photic insensitivity was apparent. Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets. These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions.

Randomized Controlled Trial

Individual thermal profiles as a basis for comfort improvement in space and other environments

BACKGROUND: The development of individualized countermeasures to address problems in thermoregulation is of considerable importance for humans in space and other extreme environments. A methodology is presented for evaluating minimal/maximal heat flux from the total human body and specific body zones, and for assessing individual differences in the efficiency of heat exchange from these body areas. The goal is to apply this information to the design of individualized protective equipment. METHODS: A multi-compartment conductive plastic tubing liquid cooling/warming garment (LCWG) was developed. Inlet water temperatures of 8-45 degrees C were imposed sequentially to specific body areas while the remainder of the garment was maintained at 33 degrees C. RESULTS: There were significant differences in heat exchange level among body zones in both the 8 degrees and 45 degrees C temperature conditions (p < 0.001). The greatest amount of heat was absorbed/released by the following areas: thighs (8 degrees C: -2.12 +/- 0.14 kcal min(-1); 45 degrees C: +1.58 +/- 0.23); torso (8 degrees C: -2.12 +/- 0.13 kcal min(-1); 45 degrees C: +1.31 +/- 0.27); calves (8 degrees C: -1.59 +/- 0.26 kcal min(-1); 45 degrees C: +1.53 +/- 0.24); and forearms (8 degrees C: -1.67 +/- 0.29 kcal x min(-1); 45 degrees C: +1.45 +/- 0.20). These are primarily zones with relatively large muscle mass and adipose tissue. Calculation of absorption/release heat rates standardized per unit tube length and flow rate instead of zonal surface area covered showed that there was significantly greater heat transfer in the head, hands, and feet (p < 0.001). The areas in which there was considerable between-subject variability in rates of heat transfer and thus most informative for individual profile design were the torso, thighs, shoulders, and calves or forearms. CONCLUSIONS: The methodology developed is sensitive to individual differences in the process of heat exchange and variations in different body areas, depending on their size and tissue mass content. The design of individual thermal profiles is feasible for better comfort of astronauts on long-duration missions and personnel in other extreme environments.

NASA Discipline Life Sciences Technologies

Controlled breaks as a fatigue countermeasure on the flight deck

BACKGROUND: A major challenge for flight crews is the need to maintain vigilance during long, highly automated nighttime flights. No system currently exists to assist in managing alertness, and countermeasure options are limited. Surveys reveal many pilots use breaks as an in-flight countermeasure, but there have been no controlled studies of their effectiveness. HYPOTHESIS: We hypothesized that brief, regular breaks could improve alertness and performance during an overnight flight. METHOD: A 6-h, uneventful, nighttime flight in a Boeing 747-400 flight simulator was flown by fourteen two-man crews. The 14 subjects in the treatment group received 5 short breaks spaced hourly during cruise; the 14 subjects in the control group received 1 break in the middle of cruise. Continuous EEG/EOG, subjective sleepiness, and psychomotor vigilance performance data were collected. RESULTS: During the latter part of the night, the treatment group showed significant reductions for 15 min post-break in slow eye movements, theta-band activity, and unintended sleep episodes compared with the control group. The treatment group reported significantly greater subjective alertness for up to 25 min post-break, with strongest effects near the time of the circadian trough. There was no evidence of objective vigilance performance improvement at 15-25 min post-break, with expected performance deterioration occurring due to elevated sleep drive and circadian time. CONCLUSIONS: The physiological and subjective data indicate the breaks reduced nighttime sleepiness for at least 15 min post-break and may have masked sleepiness for up to 25 min, suggesting the potential usefulness of short-duration breaks as an in-flight fatigue countermeasure.

Non-NASA Center

Novel method to assess gastric emptying in humans: the Pellet Gastric Emptying Test

To further validate the Pellet Gastric Emptying Test (PGET) as a marker of gastric emptying, a randomized, four-way crossover study was conducted with 12 healthy subjects. The study consisted of oral co-administration of enteric coated caffeine (CAFF) and acetaminophen (APAP) pellets in four treatment phases: Same Size (100 kcal), Fasted, Small Liquid Meal (100 kcal), and Standard Meal (847 kcal). The time of first appearance of measurable drug marker in plasma, t(initial), was taken as the emptying time for the markers. Co-administration of same size enteric coated pellets of CAFF and APAP (0.7 mm in diameter) revealed no statistically significant differences in t(initial) values indicating that emptying was dependent only on size and not on chemical make-up of the pellets. Co-administration of different size pellets indicated that the smaller 0.7-mm diameter (CAFF) pellets were emptied and absorbed significantly earlier than the larger 3.6-mm diameter (APAP) pellets with both the Small Liquid Meal (by 35 min) and the Standard Meal (by 33 min) (P<0.05). The differences in emptying of the pellets were not significant in the Fasted Phase. The results suggest that the pellet gastric emptying test could prove useful in monitoring changes in transit times in the fasted and fed states and their impact on drug absorption.

NASA Discipline Regulatory Physiology

Anatomical and functional characteristics of carotid sinus stimulation in humans

Transmission characteristics of pneumatic pressure to the carotid sinus were evaluated in 19 subjects at rest and during exercise. Either a percutaneous fluid-filled (n = 12) or balloon-tipped catheter (n = 7) was placed at the carotid bifurcation to record internal transmission of external neck pressure/neck suction (NP/NS). Sustained, 5-s pulses, and rapid ramping pulse protocols (+40 to -80 Torr) were recorded. Transmission of pressure stimuli was less with the fluid-filled catheter compared with that of the balloon-tipped catheter (65% vs. 82% negative pressure, 83% vs. 89% positive pressure; P < 0.05). Anatomical location of the carotid sinus averaged 3.2 cm (left) and 3.6 cm (right) from the gonion of the mandible with a range of 0-7.5 cm. Transmission was not altered by exercise or Valsalva maneuver, but did vary depending on the position of the carotid sinus locus beneath the sealed chamber. These data indicate that transmission of external NP/NS was higher than previously recorded in humans, and anatomical variation of carotid sinus location and equipment design can affect transmission results.

Randomized Controlled Trial

Resistance exercise countermeasures for space flight: implications of training specificity

While resistance exercise should be a logical choice for prevention of strength loss during unloading, the principle of training specificity cannot be overlooked. Our purpose was to explore training specificity in describing the effect of our constant load exercise countermeasure on isokinetic strength performance. Twelve healthy men (mean +/- SD: 28.0 +/- 5.2 years, 179.4 +/- 3.9 cm, 77.5 +/- 13.6 kg) were randomly assigned to no exercise or resistance exercise (REX) during 14 days of bed rest. REX performed five sets of leg press exercise to volitional fatigue (6-10 repetitions) every other day. Unilateral isokinetic concentric-eccentric knee extension testing performed before and on day 15 prior to reambulation included torque-velocity and power-velocity relationships at four velocities (0.52, 1.75, 2.97, and 4.19 rad s-1), torque-position relationship, and contractile work capacity (10 repetitions at 1.05 rad s-1). Two (group) x 2 (time) ANOVA revealed no group x time interactions; thus, groups were combined. Across velocities, angle-specific torque fell 18% and average power fell 20% (p < 0.05). No velocity x time or mode (concentric/eccentric) x time interactions were noted. Torque x position decreased on average 24% (p < 0.05). Total contractile work dropped 27% (p < 0.05). Results indicate bed rest induces rapid and marked reductions in strength and our constant load resistance training protocol did not prevent isokinetic strength losses. Differences between closed-chain training and open-chain testing may explain the lack of protection.

Randomized Controlled Trial

Effect of color coding and subtraction on the accuracy of contrast echocardiography

BACKGROUND: Contrast echocardiography may be used to assess myocardial perfusion. However, gray scale assessment of myocardial contrast echocardiography (MCE) is difficult because of variations in regional backscatter intensity, difficulties in distinguishing varying shades of gray, and artifacts or attenuation. We sought to determine whether the assessment of rest myocardial perfusion by MCE could be improved with subtraction and color coding. METHODS AND RESULTS: MCE was performed in 31 patients with previous myocardial infarction with a 2nd generation agent (NC100100, Nycomed AS), using harmonic triggered or continuous imaging and gain settings were kept constant throughout the study. Digitized images were post processed by subtraction of baseline from contrast data and colorized to reflect the intensity of myocardial contrast. Gray scale MCE alone, MCE images combined with baseline and subtracted colorized images were scored independently using a 16 segment model. The presence and severity of myocardial contrast abnormalities were compared with perfusion defined by rest MIBI-SPECT. Segments that were not visualized by continuous (17%) or triggered imaging (14%) after color processing were excluded from further analysis. The specificity of gray scale MCE alone (56%) or MCE combined with baseline 2D (47%) was significantly enhanced by subtraction and color coding (76%, p<0.001) of triggered images. The accuracy of the gray scale approaches (respectively 52% and 47%) was increased to 70% (p<0.001). Similarly, for continuous images, the specificity of gray scale MCE with and without baseline comparison was 23% and 42% respectively, compared with 60% after post processing (p<0.001). The accuracy of colorized images (59%) was also significantly greater than gray scale MCE (43% and 29%, p<0.001). The sensitivity of MCE for both acquisitions was not altered by subtraction. CONCLUSION: Post-processing with subtraction and color coding significantly improves the accuracy and specificity of MCE for detection of perfusion defects.

Multicenter Study

Attenuation of the protein wasting associated with bed rest by branched-chain amino acids

Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P < 0.05). Urinary 3-MeH excretion was unchanged in both groups with bed rest. We conclude that BCAA supplementation attenuates the N loss during short-term bed rest.

Randomized Controlled Trial

Acute effect of ephedrine on 24-h energy balance

Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (+/-)ephedrine in vitro to human beta1-, beta2- and beta3-adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965+/-1301 versus 8648+/-1347 kJ, P<0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 microg/mg creatinine) compared with placebo (0.044+/-0.012 microg/mg creatinine) (P<0.05). (+/-)Ephedrine is a relatively weak partial agonist of human beta1- and beta2-adrenoreceptors, and had no detectable activity at human beta3-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to beta3-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct beta1-/beta2-adrenoreceptor agonism. An indirect beta3-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.

Non-NASA Center

Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

Non-NASA Center

Hoffmann-reflex is delayed during 6 degree head-down tilt with balanced traction

BACKGROUND: Increased spinal height due to the lack of of axial compression on spinal structures in microgravity may stretch the spinal cord, cauda equina, nerve roots, and paraspinal tissues. HYPOTHESIS: Exposure to simulated microgravity causes dysfunction of nerve roots so that the synaptic portion of the Achilles tendon reflex is delayed. METHODS: Six healthy male subjects were randomly divided into two groups with three in each group. The subjects in the first group underwent horizontal bed rest (HBR) for three days. After a two week interval they underwent bed rest in a position of head-down tilt with balanced traction (HDT). So that each subject could serve as his own control, the second group was treated identically but in opposite order. Bilateral F waves and H-reflexes were measured daily (18:30-20:30) on all subjects placed in a prone position. RESULTS: By means of ANOVA, differences between HDT and HBR were observed only in M-latency and F-ratio, not in F-latency, central latency, and H-latency. Differences during the course of the bed rest were observed in M-latency and H-latency only. Tibial H latency was significantly lengthened in HDT group on day 2 and 3, although no significant difference between HDT and HBR was observed. CONCLUSION: The monosynaptic reflex assessed by H-reflex was delayed during 6 degree HDT with traction. The exact mechanism of this delay and whether the change was due to lengthening of the lower part of the vertebrae remain to be clarified.

Randomized Controlled Trial

Raised cerebrovascular resistance in idiopathic orthostatic intolerance: evidence for sympathetic vasoconstriction

Patients with idiopathic orthostatic intolerance (IOI) exhibit symptoms suggestive of cerebral hypoperfusion and an excessive decrease in cerebral blood flow associated with standing despite sustained systemic blood pressure. In 9 patients (8 women and 1 man aged 22 to 48 years) with IOI, we tested the hypothesis that volume loading (2000 cc normal saline) and alpha-adrenoreceptor agonism improve systemic hemodynamics and cerebral perfusion and that the decrease in cerebral blood flow with head-up tilt (HUT) could be attenuated by alpha-adrenoreceptor blockade with phentolamine. At 5 minutes of HUT, volume loading (-20+/-3.2 bpm) and phenylephrine (-18+/-3.4 bpm) significantly reduced upright heart rate compared with placebo; the effect was diminished at the end of HUT. Phentolamine substantially increased upright heart rate at 5 minutes (20+/-3.7 bpm) and at the end of HUT (14+/-5 bpm). With placebo, mean cerebral blood flow velocity decreased by 33+/-6% at the end of HUT. This decrease in cerebral blood flow with HUT was attenuated by all 3 interventions. We conclude that in patients with IOI, HUT causes a substantial decrease in cerebrovascular blood flow velocity. The decrease in blood flow velocity with HUT can be attenuated with interventions that improve systemic hemodynamics and therefore decrease reflex sympathetic activation. Moreover, alpha-adrenoreceptor blockade also blunts the decrease in cerebral blood flow with HUT but at the price of deteriorated systemic hemodynamics. These observations may suggest that in patients with IOI, excessive sympathetic activity contributes to the paradoxical decrease in cerebral blood flow with upright posture.

Non-NASA Center

Resistance exercise prevents plantar flexor deconditioning during bed rest

Because resistance exercise (REX) and unloading induce opposing neuromuscular adaptations, we tested the efficacy of REX against the effects of 14 d of bed rest unloading (BRU) on the plantar flexor muscle group. Sixteen men were randomly assigned to no exercise (NOE, N = 8) or REX (N = 8). REX performed 5 sets x 6-10 repetitions to failure of constant resistance concentric/eccentric plantar flexion every other day during BRU. One-repetition maximum (1RM) strength was tested on the training device. The angle-specific torque-velocity relationship across 5 velocities (0, 0.52, 1.05, 1.75, and 2.97 rad.s-1) and the full range-of-motion power-velocity relationship were assessed on a dynamometer. Torque-position analyses identified strength changes at shortened, neutral, and stretched muscle lengths. Concentric and eccentric contractile work were measured across ten repetitions at 1.05 rad.s-1. Maximal neural activation was measured by surface electromyography (EMG). 1RM decreased 9% in NOE and improved 11% in REX (P < 0.05). Concentric (0.52 and 1.05 rad.s-1), eccentric (0.52 and 2.97 rad.s-1), and isometric angle-specific torques decreased (P < 0.05) in NOE, averaging 18%, 17%, and 13%, respectively. Power dropped (P < 0.05) in NOE at three eccentric (21%) and two concentric (14%) velocities. REX protected angle-specific torque and average power at all velocities. Concentric and eccentric strength decreased at stretched (16%) and neutral (17%) muscle lengths (P < 0.05) in NOE while REX maintained or improved strength at all joint positions. Concentric (15%) and eccentric (11%) contractile work fell in NOE (P < 0.05) but not in REX. Maximal plantar flexor EMG did not change in either group. In summary, constant resistance concentric/eccentric REX completely prevented plantar flexor performance deconditioning induced by BRU. The reported benefits of REX should prove useful in prescribing exercise for astronauts in microgravity and for patients susceptible to functional decline during bed- or chair-bound hospital stays.

NASA Discipline Musculoskeletal

Subjective alertness rhythms in elderly people

The aim of this study was to evaluate age-related changes in the circadian rhythm of subjective alertness and to explore the circadian mechanisms underlying such changes. Using a visual analogue scale (VAS) instrument, 25 older men and women (71 y and older; 15 female, 10 male) rated their subjective alertness about 7 times per day during 5 baseline days of temporal isolation during which habitual bedtimes and waketimes were enforced. Comparisons were made with 13 middle-aged men (37-52 y) experiencing the same protocol. Advancing age (particularly in the men) resulted in less rhythmic alertness patterns, as indicated by lower amplitudes and less reliability of fitted 24-h sinusoids. This appeared in spite of the absence of any reliable age-related diminution in circadian temperature rhythm amplitude, thus suggesting the effect was not due to SCN weakness per se, but to weakened transduction of SCN output. In a further experiment, involving 36 h of constant wakeful bedrest, differences in the amplitude of the alertness rhythm were observed between 9 older men (79 y+), 7 older women (79 y+), and 17 young controls (9 males, 8 females, 19-28 y) suggesting that with advancing age (particularly in men) there is less rhythmic input into subjective alertness from the endogenous circadian pacemaker. These results may explain some of the nocturnal insomnia and daytime hypersomnia that afflict many elderly people.

NASA Discipline Regulatory Physiology

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

PURPOSE: To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS: Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS: After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS: Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION: We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

NASA Discipline Number 14-10

A single bout of exhaustive exercise affects integrated baroreflex function after 16 days of head-down tilt

We tested the hypothesis that one bout of maximal exercise performed 24 h before reambulation from 16 days of 6 degrees head-down tilt (HDT) could increase integrated baroreflex sensitivity. Isolated carotid-cardiac and integrated baroreflex function was assessed in seven subjects before and after two periods of HDT separated by 11 mo. On the last day of one HDT period, subjects performed a single bout of maximal cycle ergometry (exercise). Subjects did not exercise after the other HDT period (control). Carotid-cardiac baroreflex sensitivity was evaluated using a neck collar device. Integrated baroreflex function was assessed by recording heart rate (HR) and blood pressure (MAP) during a 15-s Valsalva maneuver (VM) at a controlled expiratory pressure of 30 mmHg. The ratio of change in HR to change in MAP (delta HR/ delta MAP) during phases II and IV of the VM was used as an index of cardiac baroreflex sensitivity. Baroreflex-mediated vasoconstriction was assessed by measuring the late phase II rise in MAP. Following HDT, carotid-cardiac baroreflex sensitivity was reduced (2.8 to 2.0 ms/mmHg; P = 0.05) as was delta HR/ delta MAP during phase II (-1.5 to -0.8 beats/mmHg; P = 0.002). After exercise, isolated carotid baroreflex activity and phase II delta HR/ delta MAP returned to pre-HDT levels but remained attenuated in the control condition. Phase IV delta HR/ delta MAP was not altered by HDT or exercise. The late phase II increase of MAP was 71% greater after exercise compared with control (7 vs. 2 mmHg; P = 0.041).(ABSTRACT TRUNCATED AT 250 WORDS).

Randomized Controlled Trial

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.

Randomized Controlled Trial

Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

Randomized Controlled Trial