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Neurolab (STS-90) represents a major scientific achievement that built upon the knowledge and capabilities developed during the preceding 15 successful Spacelab module missions. NASA proposed a dedicated neuroscience research flight in response to a Presidential declaration that the 1990's be the Decade of the Brain. Criteria were established for selecting research proposals in partnership with the National Institutes of Health (NM), the National Science Foundation, the Department of Defense, and a number of the International Space Agencies. The resulting Announcement of Opportunity for Neurolab in 1993 resulted in 172 proposals from scientists worldwide. After an NIH-managed peer review, NASA ultimately selected 26 proposals for flight on the Neurolab mission.

The 165 exposures from four 2-hour protocols were analyzed for correlations or trends between decompression sickness (DCS) or venous gas emboli (VGE), and variables that affect risk in the subject and astronaut populations. The assumption in this global survey is that the distributions of gender, age, body mass index, etc., are equally represented in all four tested procedures. We used Student t-test for comparisons between means and chi-square test between comparisons of proportions with p<0.05 defining a significant level. The type and distribution of the 19 cases of DCS were similar to historical cases. There was no correlation of age, gender, body mass index or fitness level with greater incidence of DCS or VGE. However increased age was associated with more Grade IV VGE in males. The duration and quantity of exercise during prebreathe is inversely related to risk of DCS and VGE. The latency time for VGE was longer (103 min +/- 56 SD, n = 15) when the ergometry was done approximately 15 min into the prebreathe than when done at the start of the prebreathe (53 min +/- 31, n = 13). The order of the ergometry did not influence the overall DCS and VGE incidence. We identified variables other than those of the prebreathe procedures that influence the DCS and VGE outcome. The analysis suggests that males over 40 years have a high incidence of Grade IV VGE.

The purpose was to develop an enhanced plan to diagnose, treat, and manage decompression sickness (DCS) during extravehicular activity (EVA). This plan is merited by the high frequency of upcoming EVAs necessary to construct and maintain the International Space Station (ISS). The upcoming ISS era will demand a significant increase in EVA. The DCS Risk and Contingency Plan provided a new and improved approach to DCS reporting, treatment, management, and training.

The majority of extravehicular activities (EVAs) performed from the shuttle use a 10.2 psi staged decompression. The International Space Station (ISS) will operate at 14.7 psi, requiring crews to "campout" in the airlock at 10.2 psi. The constraints associated with campout (crew isolation, oxygen usage, and waste management), provided the rationale to develop a 2-hour prebreathe protocol from 14.7 psi. Previous studies on the affect of microgravity and exercise during prebreathe suggested the feasibility of this approach. Various combinations of adynamia (nonwalking subjects), prebreathe exercise doses, and space suit donning options (10.2 vs. 14.7 psi) were analyzed against timeline and consumable constraints. Prospective decompression sickness (DCS) and venous gas emboli (VGE) accept/reject criteria were defined from statistical analysis of historical DCS data, combined with risk management of DCS under ISS mission circumstances. Maximum operational DCS levels were defined based on protecting for EVA capability with two crew members at 95% confidence, throughout ISS lifetime (within the constraints of NASA DCS disposition policy JPG 1800.3). The accept / reject limits were adjusted for greater safety (including Grade IV VGE criteria) based on analysis of related medical factors. Monte-Carlo simulation was performed to design a closed sequential, multi-center laboratory trial, including the capability of rejecting the primary protocol and testing at least one alternate exercise dose, within the 2-hour prebreathe. The 2-hour protocol incorporates 0, breathing for 5 0 min at 14.7 psi, including 10 min dual cycle ergometry at 75%VO(2max). It requires an additional 30 minO2breathing during depress from 14.7 to 10.2 psi, followed by a 30-60 min suit donning break at 10.2 psi/26.5% O2. It concludes with a 40 min in-suit O2 prebreathe. The protocol would be accepted for operations, if the incidence of DCS was less than 15% and Grade IV VGE less than 20%, both at 95% confidence. The above protocol and accept/reject limits were implemented in a multi-center study.

We evaluate 2-hour prebreathe protocols combining simulated microgravity and exercise during prebreathe with the objective of validating a protocol for use on International Space Station (ISS). The protocol was tested with four different exercise doses during prebreathe in a multi-center trial involving three laboratories. Subject selection, Doppler monitoring techniques for venous gas emboli (VGE), test termination criteria, and definitions of decompression sickness (DCS) were standardized in all laboratories. The Phase II protocol met the accept criteria for a prebreathe procedure for use by astronauts during assembly and maintenance of the ISS Dual-cycle ergometry or light exercise individually was not sufficient to protect against DCS at acceptable levels. The combination of both was successful.

A 10 min aerobic prebreathe exercise up to 75% V-O2(sub max) on a dual-cycle ergometer, included in the 2-hour prebreathe protocol, has been shown to dramatically reduce the incidence of decompression sickness (DCS) at altitude. In-flight only leg ergometry will be available. A balanced exercise was developed using surgical tubing with the ergometer on-orbit. We hypothesize that a 75% V02max workload, individually prescribed, would be achieved using a target heart rate to regulate the intensity of the arm exercise. VO2, heart rate (HR) / ECG, V-CO2 /V-O2, V(sub E), and V(sub T), and rate of perceived exertion (Borg scale) were measured in eleven healthy subjects who passed a US Air Force Class III Physical examination. A V-O2 peak test was performed to assess the sub-maximal exercise prescription. Two series of sub-maximal tests were performed: (1) leg ergometer/hand ergometer and (2) leg ergometer/surgical tubes. We found no significant differences (P > 0.05) in comparing the means for V-O2 and HR between the predicted and measured values during the final 4 minute-stage at "75% V-O2 workload" or between the two types of sub-maximal tests. The prescribed prebreathe sub-maximal exercise performed with flight certified surgical tubes was achieved using the target HR.

A randomized, double-blind, placebo-controlled, parallel-group, phase III multicenter trial was performed to evaluate the relative efficacy and safety of cilostazol and pentoxifylline. The study included 54 outpatient vascular clinics, including sites at Air Force, Veterans Affairs, tertiary care, and university hospitals in the United States. Of 922 consenting patients, 698 met the inclusion criteria, were randomized, and received treatment with either cilostazol 100 mg P0 twice a day, pentoxifylline 400 mg PO 3 times a day, or placebo. Treatment was double-dummy to ensure study blindness. Efficacy was primarily established by maximal walking distance (MWD), measured with constant-speed, variable-grade treadmill testing, assessed at baseline and at 4, 8, 12, 16, 20, and 24 weeks. Mean MWD of cilostazol-treated patients (n=227) was significantly improved at every visit compared with patients who received pentoxifylline (n=232) or placebo (n=239). After 24 weeks of cilostazol, mean MWD increased 53.9% (107.3 m) from baseline, and the effect had not plateaued. This was better (P < 0.001) than the 30.4% (64.4 m) MWD improvement with pentoxifylline. MWD improvement with pentoxifylline was similar (P = 0.82) to that of placebo (64.7 m). Deaths and serious adverse event rates were similar in each group. Common side effects included headache (27.8% with cilostazol, 11.2% with pentoxifylline, 11.7% with placebo), palpitations (17.2% with cilostazol, 2.2% with pentoxifylllne, 1.3% with placebo), and abnormal stools. Cilostazol was significantly better than pentoxifylline or placebo for increasing walking distances; pentoxifylline was no better than placebo.

Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of host immune rejection; (3) protection from the autoimmune component of the disease; and (4) anatomic placement of the engrafted cells that permits timely response to blood sugar levels as well as effective release and deployment of insulin. Bioreactor technology may provide some critical advances for surmounting some of these scientific hurdles. The NASA bioreactor is a horizontally rotating cylinder that is completely filled with culture medium. Gaseous exchange is maintained by a concentric cylinder of permeable silicon. In slow rotation (15-25 rpm) particles of small mass such as cells and tissue aggregates remain suspended in the rotating body of fluid. This novel approach suspends cells without stirring thus, allowing objects of different size mass to colocate and interact in a very low shear environment. In fact, analysis of the forces acting on individual cells in the rotating bioreactor reveals that the cells are continuously falling through the fluid medium. The conditions in the bioreactor permit assembly of cells into aggregates. three-dimensional tissue growth, synthesis of intercellular matrix,10 differentiation, and some sinusoid formations that may serve as a surrogate vasculature for larger tissue segments.

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 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 percent reduction) and vomiting (50 percent reduction in number of parabolas with vomiting). Side effects of the drug during flight were negligible. It is concluded that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness.

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 one 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 to the conclusion 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.