Rapid induction of protective tolerance to potential terrorist agents: a systematic review of low- and ultra-low dose research.

OBJECTIVE: To systematically review the literature on the ability of low-dose (LD) and ultra-low-dose (ULD) toxin exposure to prevent and treat biological and chemical threats. METHODS: Laboratory research articles on protection or treatment from LD or ULD exposure for the 13 high-risk chemical and biological warfare threats were collected and systematically evaluated for quantity and scientific quality using pre-defined methodological criteria. RESULTS: Over 2600 articles were screened. Only five studies met the inclusion criteria examining stimulation and protective effects of LD- or ULD-exposures to the 13 pre-identified biological and chemical agents. The quality evaluation (QE) of these studies was above average with a mean QE score of 70.6% of maximum. Two articles of fair to good quality reported both protective and treatment efficacy from exposure of animals or humans to LD- and ULD-exposures to toxins of risk in biochemical warfare. CONCLUSION: There is little research on agents of biological and chemical warfare investigating the possible use of LD- and ULD-toxins for protection and treatment. The existing literature is generally of good quality and indicates that rapid induction of protective tolerance is a feasible but under-investigated approach to bioterrorist or biowarfare defense. In our opinion, further research into the role of induced protection with LD- and ULD-toxic agents is needed.

Circulating levels of glucocorticoid hormones in WHHL and NZW rabbits: circadian cycle and response to repeated social encounter.

Social environment influences the progression of atherosclerosis in an important experimental model of disease, the Watanabe Heritable Hyperlipidemic rabbit (WHHL). Although the hypothalamic-pituitary-adrenocortical (HPA) system is likely to play an important role in the behavioral modulation of disease, relatively little is known about the glucocorticoid responses in these animals, or in other strains of rabbits. The purpose of the present study was to: (1) evaluate the rabbit glucocorticoid circadian rhythm, (2) compare plasma cortisol and corticosterone responses to social stress, and (3) examine strain differences (i.e., WHHL vs. New Zealand White (NZW)) in rabbit glucocorticoid responses to assess whether WHHLs have an aberrant HPA system. It was found that male rabbits secrete both corticosterone and cortisol in a circadian rhythm that peaks in the afternoon and reaches a nadir at 0600 h, i.e., approximately 12 h out-of-phase with the human glucocorticoid rhythm. Both glucocorticoids responded similarly to social stress induced by repeated daily 4 h pairings with another male rabbit; after 10 days of pairings, glucorticoid values were significantly correlated with the amount of defensive agonistic behavior exhibited. Finally, there were no significant strain differences in glucocorticoid circadian rhythms, baselines, or responses to social stress. These data suggest that glucocorticoid responses (i.e., circadian rhythms, responses to social stress) in the WHHL are similar to glucocorticoid responses in standard laboratory white rabbits.

Identification and expression analysis of ABC genes in Plasmodium yoelii and P. berghei.

The ATP-binding cassette (ABC) proteins are one of the largest evolutionarily conserved families. They are characterized by the presence of highly conserved nucleotide-binding sites (NBS). In the present study, we identified ABC genes in rodent Plasmodia. We queried the Plasmodium yoelii genome with the ABC signature motif and retrieved 15 contigs. Sequences were classified into seven ABC families by BLAST comparison. Conservation of the five signature ABC motifs in the P. yoelii contigs was examined by multi-alignment of the NBS. Expression of the ABC genes was examined during the blood stages of P. yoelii and P. berghei and the hepatocytic stages of P. yoelii. Our results with RT-PCR on total RNA from blood stages demonstrated the expression of 14 ABC genes in P. yoelii and ten in P. berghei. In P. yoelii hepatocytic stages, the expression of four ABC genes was detected.

Presence of platelet-activating factor in rhesus (Macaca mulatta) spermatozoa.

Platelet-activating factor [1-O-alkyl-2-acetyl-sn-glycero-phosphocholine; PAF] is a unique signaling phospholipid which has been implicated in a number of biological activities (e.g., reproduction). PAF has been detected in the spermatozoa from a number of laboratory and domestic species, including, but not limited to, rabbit, bovine, and the mouse. The concentration of PAF is inversely related to human (Homo sapien) spermatozoal quality. Additionally, PAF levels are significantly higher in Bolivian squirrel monkey (Saimiri sciureus) spermatozoa obtained during the breeding season than spermatozoa obtained during the nonbreeding season. There are no reports on the presence of PAF in rhesus (Macaca mulatta) spermatozoa. Therefore, the primary objective of this study was to detect the presence of PAF in rhesus spermatozoa. A second objective was to determine if PAF spermatozoa levels differ between animals housed individually (single-caged) versus free-ranging (open corrals). Semen were collected from mature rhesus via electro-ejaculation. Spermatozoa were washed free of ejaculatory plug and quick frozen in PBS. Endogenous lipids were extracted from thawed spermatozoa and ejaculatory plugs then assayed for the presence of PAF by [125I]-radioimmunoassay. PAF was not detected in any ejaculatory plugs. PAF levels were significantly higher (P < 0.01) in spermatozoa obtained from free-ranging males (mean: 1.16 pmol/10(6) spermatozoa) than males housed individually in single cage units (mean: 0.53 pmol/10(6) spermatozoa). PAF was present in rhesus spermatozoa. Additionally, PAF levels were higher in spermatozoa obtained from corral-housed animals. Additional studies are warranted to elucidate the role of PAF in spermatozoa function.

Optimization of single electrode tactile codes.

The effects of a frequency modulated electrocutaneous signal's (code's) characteristics on the interpretability of the signal were investigated using an electrocutaneous tracking approach. The characteristics investigated include the functional relationship (exponential and hybrid) between an informational signal and the stimulation frequency, the range of stimulation (2-50 Hz and 2-100 Hz), and the impact of pulse width compensation on a code's efficacy. The interpretability of six different single bipolar electrode codes was examined by 30 subjects using a balanced incomplete block experimental design. Codes with exponentially shaped transfer functions resulted in generally lower electrocutaneous tracking errors than codes utilizing hybrid-shaped transfer functions. Hybrid codes had a transfer function that was linear in the lower frequency range and exponential in the higher frequency range. Codes with a 2-100 Hz frequency range were interpreted better than codes with a 2-50 Hz frequency range. The use of pulse width compensation to maintain a more even level of stimulation intensity had a slightly negative effect on the subjects' abilities to cutaneously track the information signal.

Audible pedestrian traffic signals: Part 1. Prevalence and impact.

A collaborative project between the San Diego Association of Governments and San Diego State University (5) evaluated the effectiveness of audible pedestrian traffic signals in aiding visually disabled and elderly persons to walk in their community with greater safety. Three aspects of audible pedestrian traffic signals were investigated: 1) the patterns of use and the impact of these signals on pedestrian traffic safety; 2) the physical characteristics of the sound emitted by the devices; and, 3) the detection of the emitted sounds in the presence of various traffic noise levels. This paper reports on the prevalence and impact of audible traffic signals were ascertained through seeking information from traffic engineers in 71 North American cities; soliciting opinions about these signals from various school officials, social agencies, and volunteer organizations that serve persons with vision impairments; and analyzing pedestrian accident rates at intersections before and after the installation of such signals. The other two aspects of the project are reported in accompanying articles (6,7) that appear in this issue of the Journal of Rehabilitation Research and Development.

Audible pedestrian traffic signals: Part 2. Analysis of sounds emitted.

This project evaluated audible pedestrian traffic signals from three perspectives: 1) the patterns of use and the impact of these signals on pedestrian travel; 2) the physical characteristics of the sound emitted by these devices; and, 3) the detection of their emitted sounds in the presence of various traffic noise levels. This paper, the second of three companion articles (2, 3), examines the sounds emitted by the Nagoya/Traconex audible traffic signal, the unit most commonly found in the western United States and almost exclusively in California. The sounds emitted by the north-south and east-west Traconex audible signals were analyzed for their loudness, directionality, frequency spectrum, and temporal characteristics using standard engineering tools including an anechoic chamber, sound level meters, spectrum analyzers, and signal analyzers.

Audible pedestrian traffic signals: Part 3. Detectability.

This project (10) evaluated audible pedestrian traffic signals (APTS) from three perspectives: 1) the patterns of use and the impact of these signals on pedestrian travel; 2) the physical characteristics of the sound emitted by the Nagoya/Traconex APTS; and, 3) the detectability of the sounds emitted by this brand of APTS. This paper, the last of three companion articles (13,14), describes the detectability of the sounds emitted by the Nagoya/Traconex audible traffic signal, the unit most commonly found in the western United States and almost exclusively in California. To determine detectability, three groups of subjects with normal hearing--young sighted adults (controls), elderly sighted adults, and elderly blind adults--participated in an audiological study. Auditory stimuli, which consisted of APTS sounds embedded in various levels of interfering traffic noise, were presented to subjects seated inside a double-walled sound-treated chamber. The subjects were instructed to press down on a response button as soon as they heard the audible pedestrian traffic signal. The percentage of correct detections determined the absolute detectability of APTS under various S/N ratios. The subjects' speed of response indicated how quickly a pedestrian might begin to cross the intersection upon hearing the APTS.

The pulsatile portal vein in cases of congestive heart failure: correlation of duplex Doppler findings with right atrial pressures.

To better understand portal vein pulsatility in congestive heart failure, the authors compared portal vein spectral patterns to right atrial pressures measured with a Swan-Ganz catheter in 17 adult patients suspected of having congestive heart failure. Portal vein pulsatility was also evaluated in 17 healthy adults. A pulsatility score (scale, 1-5) based on a ratio of minimum to peak portal vein velocity was assigned. A score of 1 indicated continuous, monophasic flow, while a score of 5 indicated that flow reversal was observed with each cardiac cycle. All 17 healthy volunteers had portal vein pulsatility scores of 2 or less. Among the 17 patients suspected of having congestive heart failure, seven had normal right atrial pressure (less than 10 mm Hg) and pulsatility scores of 2 or less. Among the 10 patients with a right atrial pressure of 10 mm Hg or greater, six had pulsatility scores of 3 or greater (sensitivity, 60%; specificity, 100%). Greater than 50% of the variation in portal vein score is explained by changes in right atrial pressure. Review of echocardiograms in 13 of 17 patients showed no significant correlation between the degree of tricuspid regurgitation and portal vein score. Portal vein pulsatility is a sign of elevated systemic venous pressure.

Technological devices for deaf-blind children: needs and potential impact.

The authors provide a glimpse into the world of congenitally deaf-blind children and how the application of technology might enable them to lead more productive lives. They describe this population and then summarize the present status of efforts to educate and communicate with them. A review of technological devices presently usable and potentially usable to complement these efforts is given. The authors conclude with a list of technological tools that are needed for communication with deaf-blind persons.

Effects of training on human tracking of electrocutaneous signals.

The effects of training on a person's ability to perceive, interpret and utilize information presented via the tactile sense were examined by using a dual-channel electrocutaneous tracking approach. The electrocutaneous code studied was linear pulse rate encoding of information. The stimulus had a pulse width of 200 microseconds and a pulse rate between 2 and 50 pulses per second. Three tracking tasks--visual tracking, one-dimensional electrocutaneous tracking and two-dimensional electrocutaneous tracking--were performed by 20 subjects during eight to nine daily training sessions. The effects of this training regimen were found to be highly significant for both electrocutaneous tracking tasks (p less than 0.00005). The overall average improvement between successive training sessions was 21.6% for one-dimensional electrocutaneous tracking and 22.9% for two-dimensional electrocutaneous tracking. Furthermore, the rate of improvement was fastest during the initial training sessions with a slower rate of improvement seen in most subjects beginning with their fifth session. The cumulative effects of training were also reflected in the lesser amounts of practice and review required by the subjects with each succeeding test session. Results from this study can be used to estimate the amount and rate of improvement that one can expect using a typical training program for tactile sensory aids.

Relationship between pulse rate and pulse width for a constant-intensity level of electrocutaneous stimulation.

The relationship between pulse rate (PR) and pulse width (PW) for a constant level of electrocutaneous stimulation was ascertained using the method of comparative judgments. Twelve volunteer subjects were asked to adjust the PW of Comparison Stimulus (S2) until its intensity matched that of a Standard Stimulus (S1) for which the PW was 200 microseconds and PR was 10 or 20 pulses per sec (pps). As expected, the experimental results indicate that the PW of a constant-current amplitude pulse train should decrease as its PR increases if a constant level of tactile stimulation intensity is desired. However, PW and PR were not linear-inversely related (p less than 0.005). Rather, their relationship was best described by a logarithmic equation: log PW = a + b log PR, where PW is in microseconds, a is 2.82, b is -0.412, and PR is between 1 and 100 pps. Utilization of this relationship during electrical stimulation of the skin sense will decouple the intensity component of the tactile sensation from its frequency component, thereby enhancing the potential comfort and clarity of this sensory communication interface.

Evaluation of a curb-climbing aid for manual wheelchairs: considerations of stability, effort, and safety.

The experimental and theoretical procedures used to gather ergonomic data and derive theoretical estimates of stability, effort, and safety in use of a curb-climbing aid for standard manual wheelchairs are presented. The aid, intended for use of paraplegic persons, employs ramps which the user while seated in the chair can deploy and retrieve using attached telescoping rods. Ramps and rods may be carried in a ready-for-use position or stowed away in a bag hung behind the wheelchair backrest. Design, construction and method of use were described in White RN, Szeto AYJ, and Hogan HA: A practical curb-climbing aid for wheelchair-bound paraplegic patients (a progress report) Bull Prosth Res BPR 10-34 17(2):13-19 Fall 1980.

Electrocutaneous code pairs for artificial sensory communication systems.

Pairs of electrocutaneous codes suitable for dual-channel sensory communication systems were compared using a dual-channel electrocutaneous tracking task. The tracking task required the test subject to dynamically respond to changes in the tactile sensation being modulated by two independent pseudorandom signals, one for each channel. The rule (or method) by which the signals changed the tactile sensations was called an electrocutaneous code. Four frequency variation codes and two intensity variation codes were paired in different combinations and then checked as to their effectiveness for sensory communications. The experimental protocol used a balanced incomplete block design which involved 24 subjects testing 3 of 8 code pairs each. Although the variance in the tracking performances between subjects was larger than the differences between the code pairs, learning rates for the various pairs were significantly different. The easiest one to learn was the Low Pulse Rate Modulation Code paired with itself. other findings included the general superiority of monophasic stimulation code pairs over biphasic stimulation code pairs, the need for placement of the two electrodes on different dermatomes in order to achieve satisfactory dual-channel communications, and the greater sensitivity to electrocutaneous stimulation of the ventral side of the forearm versus its dorsal side.

A simulator for objectively evaluating prospective drivers of the Scott van.

A simple simulator for evaluating the physical capabilities of severely handicapped prospective drivers was developed and evaluated. The simulator presents a two-dimensional tracking task to be carried out using the driving controls of the Scott van, which is a uni-lever servo-controlled vehicle designed for the severely impaired. Twenty-five able-bodied subjects were tested on the simulator and 13 of them were then given driving tests in a Scott van. Simulator RMS tracking error and the number of traffic cones knocked down were the respective performance measures for these tests. Nine severely disabled subjects were then tested in the simulator and in driving tests in the van. In order to compare the simulator performances of the handicapped subjects with their driving performances, their performance scores were all converted to T-scores. The T-score transformed the performance of these subjects into scores having as a common reference the performances of the able-bodied subjects. Simulator T-scores for the handicapped subjects reflected large variations in their tracking abilities due to differences in their functional capabilities. Most importantly, in the authors' opinion, was the fact that the simulator T-scores of the handicapped subjects correlated very well with their driving performance T-scores. This type of simulator therefore appears to be a valuable tool for providing objective and quantitative data for evaluating severely handicapped prospective drivers.