Biomedical subjects

S A Ferguson

Publications and source records attributed to S A Ferguson.

At least 37 records · Page 2Linked to original sources

PubMed2000

Prenatal exposure to SKF-38393 alters the response to light of adult rats.

The current study examined the consequences of prenatal SKF-38393 exposure on the cellular response in the adult suprachiasmatic nuclei to light. Pregnant rats were injected with the dopamine agonist SKF-38393 or vehicle daily from gestational day 15 to 21. Adult offspring received a light pulse (1 min/2 lux) 4 or 8 h after lights off (ZT16 or ZT20 where ZT=zeitgeber time). Brains were processed for c-FOS-like immunoreactivity in the SCN. At ZT20 the number of cells expressing c-FOS protein after a light pulse was the same in both groups. At ZT16 the number of cells in the SCN of SKF-38393-exposed animals was 58% lower than the vehicle-treated group. The data suggest that prenatal SKF-38393 treatment may have long-term consequences for SCN function.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Prenatal exposure to the dopamine agonist SKF-38393 disrupts the timing of the initial response of the suprachiasmatic nucleus to light.

The abuse of social drugs such as cocaine during pregnancy represents enormous risks to the offspring. Recent studies showed that drugs administered to the pregnant rat can activate cell populations in the fetal brain, possibly altering the timing of key neuronal developmental events. The current study examined the ontogeny of light-responsiveness of the neonatal rat suprachiasmatic nucleus using c-FOS protein in SCN nuclei as a marker. The effect of acute administration of the dopamine D1 agonist, SKF-38393, on the development of light responsiveness was also examined. Pregnant dams received either SKF-38393 (10 mg/kg) or vehicle 7 h after dawn on gestational day 20. Litters were then assigned to one of seven experimental time points from 4 h after subjective dark onset on the day of birth (P0-CT16) at 4-h intervals until CT16 on the day after birth (P1-CT16). Half of the pups in each litter were exposed to a 200 lux/2 h light pulse and the other half remained in darkness. Three time points (P1-CT0, P1-CT8 and P1-CT16) were used to examine the prenatal drug effects on light-responsiveness. Light exposure at the time of subjective lights on, the day after birth (P1-CT0), resulted in a significant increase in c-FOS-positive cells. The number of positive cells recorded in the SCN after a light pulse at P1-CT0 and P1-CT8 was significantly less in SKF-38393 pretreated pups compared to vehicle treated animals. The exposure to dopaminergic stimulation during gestation may have altered the timing of development of afferent connections to the fetal SCN, resulting in alteration of the initial response of the circadian timing system to light.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2000

Impairment magnification during dynamic trunk motions.

STUDY DESIGN: An examination of a group of patients with low back disorder and a group of healthy (asymptomatic) individuals asked to produce trunk motions under sincere and insincere experimental conditions. Trunk motion components were examined to determine which combination of motion components could best distinguish between sincere and insincere efforts. OBJECTIVE: To determine whether examination of trunk motion components could be used to identify impairment magnification during unresisted repeated bending tasks. SUMMARY OF BACKGROUND DATA: Trunk motion measures can be used to assess and "benchmark" the status of the low back. However, these measures typically are clinically useful only if the individual is producing an effort that does not magnify the impairment during the functional evaluation. This study addressed the issue of impairment magnification during the production of free dynamic trunk motion. METHODS: The trunk motion characteristics of 100 healthy individuals and 100 patients with chronic low back disorders were documented. All participants were asked to produce the trunk motions in two different types of conditions. In the one experimental condition, they were asked to produce sincere trunk motions. In the other experimental condition they were asked to pretend either that they were experiencing low back pain (the asymptomatic group) or that their pain was worse than it actually was (group with low back pain). RESULTS: A combination of trunk motion measures was able to distinguish well between the conditions. Sensitivity and specificity for the asymptomatic group were 92%, whereas they were 75% for the group with low back pain. Overall, sensitivity and specificity were 81.5% for all the participants combined. CONCLUSIONS: These results indicate that motion measures can be used to help assess impairment magnification during functional trunk motion testing. These measures can provide a means by which to scrutinize the quality of quantitative measures indicating the extent of a low back disorder. These objective motion measures also can be used to complement other subjective observational methods for the assessment of impairment.

Acceleration↗

PubMed2000

Effect of Florida's graduated licensing program on the crash rate of teenage drivers.

On 1 July 1996, Florida instituted a graduated licensing program for drivers younger than age 18. For the first 3 months, holders of learner's licenses are not allowed to drive at all between 19:00 and 06:00 h; thereafter, they may drive until 22:00 h. Learner's licenses must be held for 6 months prior to eligibility for the intermediate license. Sixteen-year-old intermediate license holders are not permitted to drive unsupervised from 23:00 to 06:00 h, 17 year-olds from 01:00 to 06:00 h. All drivers younger than 18 have strict limits on the number of traffic violations they can accumulate and, effective 1 January 1997, all drivers younger than 21 are subject to a zero tolerance law for drinking and driving. Florida crash data for 1995-1997 were obtained and compared with similar data from Alabama, a state that borders Florida but does not have graduated licensing. For 15, 16, and 17 year-olds combined, there was a 9% reduction in the fatal and injury crash involvement rate in Florida during 1997, the first full year of graduated licensing, compared with 1995. On a percentage basis, crashes declined most among 15 year-olds, followed by 16 year-olds and then 17 year-olds. Reductions were not seen among Alabama teenagers nor among 18 year-olds in Florida.

Accidents, Traffic↗

PubMed2000

Neck pain and head restraint position relative to the driver's head in rear-end collisions.

This two-year investigation was designed to estimate the incidence of driver neck pain in rear-struck vehicles involved in two-vehicle collisions and to determine the relationship between neck pain and specific vehicle, human, and environmental factors. Neck pain percentages were significantly higher for female (45%) than for male (28%) drivers. For female and male drivers, neck pain likelihood increased as head restraint height decreased below the head's center of gravity, although this effect was significant only for females. Head restraint backset, the horizontal distance measured from the back of the driver's head to the front of the head restraint, was not found to be related to neck pain for female drivers. Backset trends for male drivers could not be evaluated because few male drivers had head restraints that were high enough for backset to be relevant. Reported neck pain decreased for older drivers (females only), drivers in less severe crashes, and drivers in heavier cars (females only); all head restraint analyses were adjusted for these characteristics. Women, and most likely men, in the United States would benefit greatly from international harmonization to European head restraint standards. Until then, both women and men should be encouraged to adjust their adjustable head restraints, if possible, behind their heads' centers of gravity and to sit with the backs of their heads as close as possible to their head restraints.

Accidents, Traffic↗

PubMed2000

An evaluation of l-ephedrine neurotoxicity with respect to hyperthermia and caudate/putamen microdialysate levels of ephedrine, dopamine, serotonin, and glutamate.

l-Ephedrine is an active ingredient in several herbal formulations with a mechanism of action similar to amphetamine and methamphetamine. However, its potential to damage dopaminergic terminals in the caudate/putamen (CPu) has yet to be fully evaluated. The studies here used in vivo brain microdialysis experiments to determine the systemic doses and extracellular brain levels of l-ephedrine necessary to produce similar increases in CPu extracellular dopamine and marked hyperthermia that were previously shown necessary for amphetamine-induced neurotoxicity in male Sprague-Dawley rats. At an environmental temperature of 23 degrees C, a single 40 mg/kg intraperitoneal (ip) dose of l-ephedrine produced marked hyperthermia (>/= 40 degrees C), peak microdialysate ephedrine levels of 7.3 +/- 1.2 microM, and a 20-fold increase in microdialysate dopamine levels. Twenty-five mg/kg produced a lesser degree of hyperthermia, peak microdialysate ephedrine levels of 2.6 +/- 0.4 microM, and a 10-fold increase in dopamine levels. Three doses of 40 mg/kg given at 3-h intervals or 4 doses of 25 mg/kg l-ephedrine given at 2-h intervals were compared with 4 doses of 5 mg/kg d-amphetamine given at 2-h intervals. Multiple doses of either ephedrine or amphetamine caused severe hyperthermia (>/= 41.3 degrees C) but striatal tissue levels of dopamine 7 days after dosing were reduced only 25% or less by ephedrine compared to the 75% reductions produced by amphetamine. The increases in CPu microdialysate levels of serotonin produced by either 4 x 25 mg/kg l-ephedrine or 4 x 5 mg/kg d-amphetamine did not significantly differ, but elevation of dopamine levels by d-amphetamine were over 2-fold times the level caused by l-ephedrine. Microdialysate glutamate levels were elevated to the same extent by either 25 mg/kg l-ephedrine or 4 x 5 mg/kg d-amphetamine. l-Ephedrine may not be as neurotoxic to dopaminergic terminals as d-amphetamine, because non-lethal doses of l-ephedrine do not sufficiently increase the CPu dopamine levels within nerve terminals or the extracellular space to those necessary for a more pronounced long-term dopamine depletion.

Animals↗

PubMed2000

Effects of genistein exposure on sexually dimorphic behaviors in rats.

The phytoestrogen genistein, the principal isoflavone in soybeans, has adverse effects on animal reproduction. As adult physiology and behavior are sensitive to perturbation by developmental estrogens, exposure to genistein during development may produce behavioral alterations as well. Pregnant rats were fed soy-free diets containing 0, 25, 250, or 1250 ppm genistein (approximately 0, 2, 20, or 100 mg/kg/day) beginning on gestational day 7, and offspring continued on these diets through postnatal day (PND) 77. Male and female offspring were assessed for levels of sexually dimorphic behaviors: open field activity, play behavior, running wheel activity, and consumption of saccharin- and sodium chloride-flavored solutions. Consumption of the salt solution was affected by genistein, with animals in the 1250-ppm group drinking significantly more than controls; consumption of plain water was unaffected. Genistein treatment also significantly affected play behavior; although no treated group was significantly different from controls, and the effect was not sexually dimorphic. Running wheel activity and saccharin solution consumption showed significant sex differences, but no effects of genistein treatment. Gestational duration, total and live pups per litter, and total and live litter sex ratios were not significantly affected by genistein. However, average weight per live pup at birth and offspring body weights from PND 42-77 were significantly decreased in the 1250-ppm group. Body weight and food intake for the dams were also significantly decreased in the 1250-ppm group. These results indicate that developmental genistein treatment, at levels that decrease maternal and offspring body weight, causes subtle alterations in some sexually dimorphic behaviors.

Animals↗

PubMed2000

Acute effects of cocaine on play behaviour of rats.

Play behaviours are exhibited by many mammalian species. The similarity of such behaviour across children, non-human primates and rats makes it an especially appropriate target for the investigation of drug- or toxicant-induced disruption. In this study the acute effects of cocaine on play behaviour in male and female Sprague-Dawley rats was assessed. Same-sex dyads of rats (postnatal day 35-36) were separated 24 h prior to testing. On the following day, one or both rats of the dyad were injected with the same dose of cocaine (0, 2.5, 5.0 or 20.00 mg/kg). Thirty minutes later the rats were placed together and, after 5 min of habituation, the frequency of pins and crawl-overs were measured for each subject. In dyads in which both rats were treated, crawl-overs and pinning behaviour were decreased by 20 mg/kg cocaine. In dyads in which only one rat was treated, there was marginal effect of cocaine treatment on pinning frequency, while crawl-overs were unaffected. Pinning frequency was not sexually dimorphic in either type of dyad; however, crawl-overs were more frequently exhibited by females in dyads in which only one rat was treated. Thus, pinning behaviour in juvenile rats appears somewhat more sensitive to cocaine-induced disruption than crawl-over behaviours. Additionally, the presence of an untreated rat appears to attenuate the play-disrupting effects of cocaine on pinning frequency.

Animals↗

PubMed2000

Child seating position and restraint use in three states.

OBJECTIVE: Because of risks from deploying airbags to children in front seats, extensive publicity has been aimed at getting them restrained and in rear seats. The objective of this study was to assess restraint use and seating positions among children in vehicles with and without airbags. METHOD: Surveys were conducted in cities in Michigan, North Carolina, and Texas 1998. Restraint use and seating position were noted for all children, as well as their estimated age, driver belt use, airbag presence, and vehicle license plate number. RESULTS: Fewer children were observed in the front seats of vehicles with passenger airbags (24%) than in vehicles without them (36%). Most of the children seated in front were ages 7-12 (44%-61%), followed by 3-6 year olds (29%-35%). Very few children ages 0-2 were seated in front (5%-12%). The overwhelming majority of children ages 0-2 were restrained. However, children ages 3-6 seated in the front were least likely to be restrained and most likely to be improperly restrained. Restraint use was higher when the driver was belted, but about 30% of 3-6 year olds were unrestrained even with a belted driver. CONCLUSIONS: Efforts should continue to educate parents about the importance of correct restraint use and rear seating for children, particularly once children move from child safety seats into adult belts. Efforts also should be made to enforce the seat belt laws that exist in every state.

Accident Prevention↗

PubMed2000

Variations in teenage activities with and without a driver's license.

High school students were surveyed every 6 months from their freshman through senior years concerning licensing, driving, and transportation to and from their various activities. Students in Delaware (learner's permit can be issued at age 15 years, 10 months; driver's license at age 16) were compared with students in Connecticut and New York (permit at age 16; license at age 16) and in New Jersey (license at age 17). During the junior year, most Delaware students, some New York and Connecticut students, and few New Jersey students were licensed. However, even during the junior year, students in the respective states did not differ significantly with respect to time spent at activities such as a paying job, homework, watching television, dating, parties, being with friends, talking on the phone, or participating in sports or school activities. Graduated licensing systems can delay full-privilege teenage licensure and reduce teenage crash rates. These systems also can increase the number of times parents and others must drive. However, the present study's results indicate that licensing delays of as much as 1 year have minimal effects on the nondriving activities of high school students.

Adolescent↗

PubMed2000

Developmental neurotoxicity of endocrine disrupters: focus on estrogens.

A number of different environmental compounds are proposed to interact with the endocrine system (i.e., endocrine disrupters). Many of these have estrogenic effects in vitro and/or in vivo. Recent reviews have focused attention on the need for assessing the neurotoxicity of these compounds following developmental exposure. This attention comes in part from the literature on the effects of developmental exposure to exogenous estrogen on later behavioral and neuropathological alterations. A review of the ongoing neurobehavioral and neuropathological studies at the National Center for Toxicological Research on four such estrogen mimics (genistein, methoxychlor, nonylphenol, and ethinyl estradiol) is presented with results indicating that intake of a sodium solution is sensitive to these estrogen mimics. Developmental dietary exposure in male and female rats resulted in increased consumption of the sodium solution. Volume of the sexually dimorphic nucleus of the medial preoptic area was reduced by genistein, nonylphenol, and ethinyl estradiol exposure in males. The regulatory impact of these data and the directions for future research are discussed.

Animals↗

PubMed2000

Multigenerational exposure to dietary genistein has no severe effects on nursing behavior in rats.

The phytoestrogen and principal isoflavone in soy, genistein, has adverse effects on reproductive physiology in rodents. Since physiology and behavior are both sensitive to perturbations by estrogens, genistein may produce behavioral alterations as well. This paper reports one aspect of a study in which several adult rodent behaviors will be assessed following long term multigenerational dietary exposure to genistein. Since maternal care may affect offspring behaviors in adulthood, it is important to determine the potential for genistein to affect maternal behavior. Here, rats (F0 generation) were fed soy-free diets containing 0, 5, 100, or 500 ppm genistein (approx. 0, 0.4, 8, and 40 mg/kg/day for an adult) beginning on postnatal day (PND) 42. Two generations of offspring (F1 and F2) were continued on these diets and all treatment groups of the F3 generation were returned to 0 ppm at weaning (PND 22). In the first 3 weeks after parturition (for each generation), dams were assessed on 6 occasions for the presence of the arched back posture with at least one pup nursing. Data were analyzed by 3 way repeated measures analysis of variance (ANOVA) with generation, treatment, and postnatal day as factors, and p<0.05 required for significance. There were no significant interactions among treatment, generation, or day, and no overall effects of treatment or generation. As expected, there was a significant overall effect of day, with animals nursing less on later days (p<0.0001). As assessed here, these results suggest that lifelong and multigenerational exposure to dietary genistein has no severe effects on nursing behavior in rodents.

Animals↗

PubMed1999

The quantification of low back disorder using motion measures. Methodology and validation.

STUDY DESIGN: Trunk angular motion features were used as a means to quantify the extent of a low back disorder in healthy people and patients with chronic low back disorders. OBJECTIVE: To refine and validate a previously reported means of quantifying the extent of a low back disorder. SUMMARY AND BACKGROUND: Many assessment tools of low back disorder are subjective. A quantitative assessment tool would facilitate the tracking of the recovery and help document the appropriateness of treatments. METHODS: The trunk motion characteristics of 374 healthy people and 335 patients with chronic low back disorders of varying severity were documented as they flexed and extended their trunks in five different planes of motion. The trunk motion features were normalized as a function of age and gender. Four classification techniques were used to assess the ability of the quantitative motion measure to identify those with and without low back disorders. In addition, 31 patients were observed longitudinally to determine whether the motion measures agreed with observed changes in back pain symptoms. RESULTS: The quantitative trunk motion measure distinguished between people with low back disorders and healthy people between 88% and 94% of the time, depending on which classification system was used. Sensitivity and specificity varied between 83% and 97%. The quantitative measure also showed promise as a means to distinguish between muscle-based and structure-based low back disorders. Prospective findings indicated that the quantification system agreed well with clinical observations of progress. CONCLUSIONS: The quantification of trunk motion can serve as a measure of the extent of a low back disorder. When considered along with other clinical information, the ability to assess and treat low back disorders is enhanced.

Adult↗

PubMed1999

Nicotine phase shifts the 6-sulphatoxymelatonin rhythm and induces c-Fos in the SCN of rats.

The neurotransmitter acetylcholine is not found in the major suprachiasmatic nuclei afferents reported to mediate light effects on entrainment and phase shifts in mammals; however it clearly has some role in the control of circadian rhythmicity. This study examined the effect of the cholinergic agonists nicotine and oxotremorine on (1) the rhythmic production of melatonin using the metabolite, 6-sulphatoxymelatonin as a marker, and (2) the expression of c-Fos protein in the suprachiasmatic nuclei (SCN) of the rat. Nicotine administration (1 mg/kg, s.c.) caused phase delays in the timing of the onset of 6-sulphatoxymelatonin excretion (compared to the pre-treatment night), when administered at circadian time (CT)16 (1.7+/-0.3 h delay) and CT18 (1.7+/-0.2 h delay) but not at CT14 (0.8+/-0.3 h delay), whereas oxotremorine and saline administration had no effect on the timing of the melatonin rhythm. Nicotine administration also caused the induction of c-Fos-like immunoreactivity in the SCN in a dose- and time-dependent manner. Further, pre-treatment with the nicotinic antagonist mecamylamine reduced the number of nicotine-induced c-Fos-positive cells in the SCN by 65%. These data indicate that cholinergic neurons may alter the timing of the onset of melatonin excretion by a direct or indirect effect on the SCN possibly mediated by the nicotinic receptor.

Animals↗

PubMed1999

The effectiveness of commonly used lifting assessment methods to identify industrial jobs associated with elevated risk of low-back disorders.

Low-back disorders (LBD) continue to be the most costly and common musculoskeletal problem facing society today. Investigators have developed tools or measures that are intended to identify jobs that will probably be associated with an elevated risk of low-back disorders. However, an important and not widely discussed issue associated with these tools and procedures has been that of the validity or effectiveness of the tools. Therefore the objective of this study was to evaluate the validity and effectiveness of two commonly used types of LBD assessment methods in terms of their ability to correctly associate jobs with LBD risk. The 1981 NIOSH Work Practices Guide for Manual Lifting and the 1991 NIOSH revised lifting equation, along with psychophysical measures were assessed for their ability to correctly identify high-, medium-, and low-risk (of LBD) jobs. Risk was defined according to a database of 353 industrial jobs representing over 21 million person-hours of exposure. The results indicated that both NIOSH measures were predictive and resulted in odds ratios between 3.1 and 4.6. Higher odds ratios were found when the maximum horizontal distance was used to assess a job compared to the average horizontal distance. Further analyses indicated that the two NIOSH assessment methods classified risk in very different ways. The 1981 NIOSH Guide demonstrated good specificity (91%) in that it identified low-risk jobs well but it also displayed low sensitivity by only correctly identifying 10% of the high-risk jobs. The 1993 NIOSH revised lifting equation, on the other hand, had better sensitivity. It correctly identified 73% of the high-risk jobs but did not identify low- and medium-risk jobs well. Using psychophysical criteria it was observed that 60% of the high-risk jobs would be judged to be acceptable, whereas, 64% and 91% of the medium- and low-risk jobs, respectively, would be judged to be acceptable. This study indicates that the different measures have various strengths and weaknesses. When controlling for occupational LBD it should be recognized that a variety of measures exist and that the measure that most appropriately assesses risk depends upon the characteristics of the job.

Databases, Factual↗

PubMed1999

Emergence of altered circadian timing in a cholinergically supersensitive rat line.

Mammalian circadian rhythms are controlled by the suprachiasmatic nuclei (SCN) in concert with light information. Several neurotransmitters and neural pathways modulate light effects on SCN timing. This study used a line of rat with an upregulated cholinergic system to investigate the role of acetylcholine in rhythmicity. With the use of a selective breeding program based on the thermic response to a cholinergic agonist, we developed a supersensitive (S(ox)) and subsensitive (R(ox)) rat line. The S(ox) rats showed an earlier onset time of melatonin rhythm under a 12:12-h light-dark photoperiod from generation 3 (3 +/- 0.5 h after dark) compared with R(ox) rats (4.5 +/- 0.1 h) and an earlier morning decline in temperature (0.9 +/- 0.3 h before lights on) compared with R(ox) animals (0.1 +/- 0.1 h). Furthermore, the S(ox) animals displayed a significantly shorter free-running period of temperature rhythm than R(ox) rats (23.9 +/- 0.04 and 24.3 +/- 0.1 h, respectively, P < 0.05). The results suggest that the altered circadian timing of the S(ox) rats may be related to the cholinergic supersensitivity, intimating a role for acetylcholine in the circadian timing system.

Acetylcholine↗

PubMed1998

The effect of teenage passengers on the fatal crash risk of teenage drivers.

Fatal crash-involved drivers of passenger vehicles were identified in the Fatality Analysis Reporting System for the period 1990 through 1995. Each driver was categorized as being alone in the vehicle at the time of the crash or with one or more passengers. Drivers at fault or responsible for crash occurrence were defined as all drivers involved in a single-vehicle crash, or drivers in multiple-vehicle crashes who were coded in the Fatality Analysis Reporting System as committing one or more driver errors. The results indicated that passenger presence was associated with proportionately more at-fault fatal crashes for drivers aged 24 and younger, were a neutral factor for drivers aged 25-29, and were associated with fewer at-fault involvements for drivers aged 30 and older. Relative risk of fatal crash involvement was particularly high for teenage drivers traveling, day or night, with two or more teenage passengers. Additional research is needed to determine how the added risk associated with teenage passengers riding with teenage drivers can be reduced or eliminated.

Accidents, Traffic↗

PubMed1998

Fatal crash risk for older drivers at intersections.

Risk of fatal crash involvement was calculated for older drivers relative to drivers aged 40-49 in the United States during the years 1994-1995. The results indicated that drivers ages 65-69 were 2.26 times more at risk for multiple-vehicle involvements at intersections compared with 1.29 times more at risk in all other situations. The comparable figures for drivers aged 85 and older were 10.62 for multiple-vehicle involvements at intersections compared with 3.74 for all other situations. The relative crash risk was particularly high for older drivers at uncontrolled and stop sign-controlled locations; when traveling straight or when just starting to enter the intersection; and when the specific behavioral error in the crash was failure to yield. Countermeasures will likely involve reducing or simplifying the need to detect and evaluate moving traffic coming from the left and right when at intersections. This can be accomplished by traffic signals with protected left turns, four-way stop signs, and one-way streets. Whereas such devices involve significant cost in terms of dollars and travel delay, their cost-effectiveness may have to be revisited as the United States population continues to age.

Accidents, Traffic↗