Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density.

UNLABELLED: We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90% at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. INTRODUCTION: The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. METHODS: Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. RESULTS: One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89% (95%CI 82-96%) and 41% (95%CI 23-59%), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88% (95%CI 79-97%) and 55% (95%CI 42-68%), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90% but always with a trade-off of relatively low specificity. CONCLUSIONS: Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90% for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments.

The effect of tendon vibration on motor unit activity, intermuscular coherence and force steadiness in the elbow flexors of males and females.

BACKGROUND: Compartmentalized responses in motor unit (MU) activity of the short head (SH) and long head (LH) of the biceps brachii are observed following forearm position change. Differential muscle spindle afferent distribution has been proposed as a potential mechanism underlying this behaviour. Tendon vibration is an effective, non-invasive method of increasing muscle spindle afferent activity of a target muscle group offering a paradigm in which this hypothesis may be investigated further. AIM: To determine the effect of tendon vibration on MU recruitment and discharge rates of the SH and LH, muscle activity of the elbow flexors and triceps brachii, intermuscular coherence among the SH, LH, brachioradialis and triceps brachii and force steadiness in young males and females during isometric elbow flexion. METHODS: Intramuscular electromyography (EMG) of the SH and LH, and surface EMG of the elbow flexors were recorded pre- and post-vibration during low-force isometric contractions. Motor unit recruitment thresholds, MU discharge rates and MU discharge variability; surface EMG amplitude, intermuscular coherence and force steadiness were determined pre- and post-vibration. RESULTS: Differential changes in all MU properties, EMG amplitude and intermuscular coherence were observed among elbow flexors. Although MU properties exhibited differential changes, they accounted for little variance in isometric force steadiness. However, intermuscular EMG coherence among all muscles investigated was reduced post-vibration. CONCLUSION: Uncoupling of common oscillatory input as a result of differential muscle spindle afferent inputs to elbow flexors may be responsible for the reduction in force steadiness following tendon vibration and a forearm position change.

Performance of risk assessment instruments for predicting osteoporotic fracture risk: a systematic review.

UNLABELLED: We systematically reviewed the literature on the performance of osteoporosis absolute fracture risk assessment instruments. Relatively few studies have evaluated the calibration of instruments in populations separate from their development cohorts, and findings are mixed. Many studies had methodological limitations making susceptibility to bias a concern. INTRODUCTION: The aim of this study was to systematically review the literature on the performance of osteoporosis clinical fracture risk assessment instruments for predicting absolute fracture risk, or calibration, in populations other than their derivation cohorts. METHODS: We performed a systematic review, and MEDLINE, Embase, Cochrane Library, and multiple other literature sources were searched. Inclusion and exclusion criteria were applied and data extracted, including information about study participants, study design, potential sources of bias, and predicted and observed fracture probabilities. RESULTS: A total of 19,949 unique records were identified for review. Fourteen studies met inclusion criteria. There was substantial heterogeneity among included studies. Six studies assessed the WHO's Fracture Risk Assessment (FRAX) instrument in five separate cohorts, and a variety of risk assessment instruments were evaluated in the remainder of the studies. Approximately half found good instrument calibration, with observed fracture probabilities being close to predicted probabilities for different risk categories. Studies that assessed the calibration of FRAX found mixed performance in different populations. A similar proportion of studies that evaluated simple risk assessment instruments (≤5 variables) found good calibration when compared with studies that assessed complex instruments (>5 variables). Many studies had methodological features making them susceptible to bias. CONCLUSIONS: Few studies have evaluated the performance or calibration of osteoporosis fracture risk assessment instruments in populations separate from their development cohorts. Findings are mixed, and many studies had methodological limitations making susceptibility to bias a possibility, raising concerns about use of these tools outside of the original derivation cohorts. Further studies are needed to assess the calibration of instruments in different populations prior to widespread use.

Effects of vicariant barriers, habitat stability, population isolation and environmental features on species divergence in the south-western Australian coastal reptile community.

Identifying explicit hypotheses regarding the factors determining genetic structuring within species can be difficult, especially in species distributed in historically dynamic regions. To contend with these challenges, we use a framework that combines species distribution models, environmental data and multi-locus genetic data to generate and explore phylogeographic hypotheses for reptile species occupying the coastal sand-dune and sand-plain habitats of the south-western Australian biodiversity hotspot, a community which has both a high diversity of endemics and has varied dramatically in spatial extent over time. We use hierarchical amova, summary statistic and distance-based analyses to explicitly test specific phylogeographic hypotheses. Namely, we test if biogeographic vicariance across barriers, habitat stability, population isolation along a linear habitat or fragmentation across different environments can explain genetic divergence within five co-distributed squamate reptile species. Our results show that patterns of genetic variation reflect complex and species-specific interactions related to the spatial distribution of habitats present currently and during repeated glacial minima, as opposed to being associated with historical factors such as habitat stability between glacial and inter-glacial periods or vicariant barriers. We suggest that the large impact of habitat characteristics over time (i.e. relative levels of habitat connectivity, climatic gradients and spatial heterogeneity of soil types) reflects the ecological restrictions of the sand-dune and sand-plain reptile communities and may explain the lack of concordance across taxa. The study demonstrates the general utility of the approach for assemblage-level, as well as single species, phylogeographic study, including its usefulness for exploring biologically informed hypotheses about what factors have influenced patterns of genetic variation.

Morphological differentiation correlates with ecological but not with genetic divergence in a Gehyra gecko.

Body size affects life history, the ecological niche of an organism and its interactions with other organisms. Resultantly, marked differences in body size between related organisms are often an indication of a species boundary. This is particularly evident in the Gehyra variegata species complex of geckos, which displays differential body sizes between genetically divergent species, but high levels of intraspecific morphological conservatism. We report on a Gehyra population that displays extraordinary body size differentiation in comparison with other G. variegata species. We used morphological and environmental data to show this population is phenotypically and ecologically distinct from its parapatric congener Gehyra lazelli and that morphology and ecology are significantly correlated. Contrastingly, mtDNA analysis indicates paraphyly between the two groups, and allele frequencies at six microsatellite loci show no population structure concordant with morpho-/ecotype. These results suggest either ecological speciation or environmentally induced phenotypic polymorphism, in an otherwise morphologically conservative group.

Age- and sex-related differences for electromyography gaps during daily activity and a discrete task.

Temporal patterns of quiescent electromyography termed 'gaps' were investigated in young and old men and women for a discrete task and daily activity. Gaps in women (1.3±3.2) and old adults (1.5±3.4) were fewer compared with men (4.7±6.7) and young adults (4.6±6.9) for the discrete task (p<0.001). Gap duration was shorter for women (0.1±0.2s) and old adults (0.1±0.3s) compared with men (0.2±0.3s) and young adults (0.2±0.2s) (p<0.01). For daily activity, gap number was similar with age, but gap duration and percentage of total time occupied by gaps were less in old compared with young adults (50%), and in women compared with men (43%) (p<0.001). Results suggest gap activity is sensitive to type and duration of activity and that old adults and women demonstrate less quiescent electromyography than young adults and men.

Age independent and position-dependent alterations in motor unit activity of the biceps brachii.

In the biceps brachii, age-related differences in synaptic excitability and muscle architecture may affect motor unit (MU) activity differently depending on the position of the forearm. It was hypothesised that as a result of these age-related differences, greater changes in MU activity would accompany a change in forearm position in old when compared with young men. Six young (22 +/- 3 years) and six old (84 +/- 3 years) men maintained isometric elbow flexion at 10% of maximal voluntary contraction (MVC) during changes in forearm position. Forty-nine MUs in the short (SBB) and long (LBB) heads of the biceps brachii were followed. Motor unit recruitment and de-recruitment thresholds, motor unit discharge rates (MUDRs), and MU discharge variability were measured. Although an age-related decrease in MU recruitment thresholds, and increase in MU discharge variability was evident, changes in forearm position influenced MUDRs similarly in young and old men (P = 0.27). Motor unit recruitment thresholds of the SBB were highest in the pronated position (8.2 +/- 2.9 %MVC), whereas in the LBB they were highest in the supinated position (8.6 +/- 2.0 %MVC). Motor unit discharge rates of the LBB did not change with forearm position. In the SBB, MUDRs were highest when the forearm was supinated, and also greater when compared with the LBB in this position. No position-dependent changes were observed for MU discharge variability in the LBB, but the SBB exhibited greatest MU discharge variability in the pronated position. The results suggest that MU activity is modulated following a change in forearm position, but the response is similar in young and old adults.

Age- and sex-related differences in muscle activation for a discrete functional task.

Electromyography (EMG) recordings for a typical 8-h day have indicated that burst activity is greater in old adults compared with young adults; these age-related adaptations might be due to the tasks undertaken. The purpose of the present study was to determine whether EMG burst activity differs between young and old men and women for a discrete task of daily living, and to assess whether the time of day when the task is performed influences the EMG burst patterns. Subjects completed a discrete functional task of a grocery bag carry prior to and following 8 h of daily activity. Surface EMG was recorded from the biceps brachii, triceps brachii, vastus lateralis, and biceps femoris. Spatial and temporal characteristics of the bursts were quantified as a period of EMG activity being greater than 2% maximum EMG and for a duration longer than 0.1 s. Burst activity did not differ between the morning and evening recordings, which indicate that the time of day does not influence burst activity recorded for a discrete task. Although there were no differences in burst number between young (10.9 +/- 1.0) and old (11.4 +/- 0.7) adults, burst duration and area were 3-7 times larger in old adults compared with young adults. The number of bursts in women (7.9 +/- 1.0) were ~85% less compared with men (14.6 +/- 0.7), but burst duration and burst area were approximately three times larger in women compared with men. Thus, older adults demonstrate higher levels of burst activity compared with young adults, and these age-related changes in burst activity are augmented in women.

Effect of sperm concentration, medium osmolality and oocyte storage on artificial fertilisation success in a myobatrachid frog (Limnodynastes tasmaniensis).

The present study optimised artificial fertilisation and oocyte storage conditions in Limnodynastes tasmaniensis (Myobatrachidae). Data on general reproductive biology, the effect of sperm motility and concentration, medium osmolality and oocyte storage on artificial fertilisation success are presented. Egg number was most strongly correlated with bodyweight (r = 0.819). Sperm yield was correlated with testes weight (r = 0.827), which was strongly correlated with snout-vent length (r = 0.772). Optimal artificial fertilisation occurred in 0-7 mOsm kg(-1) amphibian Ringer, similar to ranid, bufonid and hylid species. High fertilisation rates were achieved using spermatozoa with little forwards progressive motility at comparatively low concentrations (3 x10(4) sperm cells mL(-1)) and with no relationship between percentage sperm motility and fertilisation success (correlation of fertilisation rate with sperm motility after activation: r = -0.145). Oocytes stored in 5 mOsm kg(-1) solutions showed no significant decline in fertilisability after 2 h, showing that swelling of the jelly surrounding the eggs does not prevent sperm from fusing with the oocyte in this species. Fertilisability of oocytes was extended to > 4 h in medium to high osmolality solutions (124-271 mOsm kg(-1)). These data allow for the future use of L. tasmaniensis in developing assisted reproductive technology protocols for foam-nesting myobatrachid species, many of which are now threatened with extinction in the wild.

Evaluation of sampling locations for two radionuclide air-sampling systems based on the requirements of ANSI/HPS N13.1-1999.

The Pacific Northwest National Laboratory characterized the performance of sampling locations for two radionuclide air-sampling systems that continuously monitor radioactive air emissions from research and development facilities. The testing was conducted to determine whether sampling system locations would meet the criteria for uniform air velocity and contaminant concentration in the American National Standard Institute standard, Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stacks and Ducts of Nuclear Facilities (ANSI/HPS N13.1-1999). The standard is a revision of the 1969 version that the facilities have been required to meet. Whereas the 1969 standard provided prescriptive criteria for the selection of sampling locations, the 1999 standard is performance-based and requires well-mixed sampling locations that must be demonstrated through performance tests that are specified in the standard. Testing at the Life Sciences Laboratory I was performed on the existing stack at the current sampling location; a scale model was built and used in place of the Radiochemical Processing Laboratory. Although both facilities' sampling sites were compliant with the 1969 standard, only the Radiochemical Processing Laboratory met the criteria of the revised standard. In the future, the use of a computational fluid dynamics computer model may be useful in determining whether a sampling location is likely to test successfully.

Results of inspection and cleaning of two radionuclide air-sampling systems based on the requirements of ANSI/HPS N13.1-1999.

The Pacific Northwest National Laboratory inspected and cleaned two radionuclide air-sampling systems that continuously monitor radioactive air emissions from research and development facilities. The inspection and cleaning was performed to evaluate effective methods and potential cost impacts of maintenance requirements in the revised American National Standard Institute standard Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stacks and Ducts of Nuclear Facilities. The standard requires at least annual inspections of sampling systems followed by cleaning if deposits are visible. During 2001 and 2002, inspections were performed leaving the sampling systems in place and inserting videoscope cables into different access points to allow viewing of the inside and outside of sampling manifolds and transport lines. Cleaning was performed on one of the systems by disconnecting and extracting the sampling manifold, then washing it with de-ionized water and scrub brushes. The wash water was analyzed for radioactivity and solids. Results of the inspection showed greater deposition in one of the systems than would be expected by a High Efficiency Particulate Air (HEPA) filtered exhaust stream, possibly due to accumulation of dust from a short period when unfiltered air was exhausted from construction areas. The second system was also downstream of HEPA filters and appeared much cleaner. The videoscope was a useful and cost-effective tool and provided a better view than could be obtained with the naked eye. However, because even small amounts of deposition were made visible with the videoscope, clarification is needed in defining when probe washing is merited, particularly in existing sampling systems whose design is not conducive to easy removal and cleaning.

AZT distribution in the fetal and postnatal rat central nervous system.

The distribution of 3'-azido-3'-deoxythymidine (AZT, zidovudine), an antiviral drug used in the treatment of human immunodeficiency virus, was investigated in gestation day-20 (G-20) fetuses and in postnatal day-20 (PND-20) rats. At both ages, a single dose of 150 mg/kg (1.78 mmol/kg) AZT was administered orally along with tracer amounts of 14C-AZT, and rats were randomly killed at 15, 30, 60, 120, or 240 min after dosing. The fetuses, brains, and spinal cords were processed for autoradiography. The peak concentrations of AZT in plasma of G-20 and PND-20 rats were 92.2 microg/mL (0.345 micromol/mL) and 56.6 microg/mL (0.21 micromol/mL) at 15 and 30 min after intubation, respectively. The peak concentration of fetal tissue occurred in the colon at 60 min and was 205.8 microg/g tissue. In the G-20 rats, the brain showed higher levels of AZT than spinal cord only at the 30-min sample time, whereas in the PND-20 rats, greater radioactivity was found in the spinal cord up to the 240-min sample time. This pattern of AZT distribution in the central nervous system may hypothetically be attributed to the postnatal development of an organic anion carrier system believed to be responsible for transporting AZT from the brain to the blood, resulting in relatively greater overall exposure of the spinal cord to AZT than observed in the brain.

Impairment of spatial learning following preweaning cocaine exposure in the adult rat.

The present investigation focuses on learning and working memory capabilities of adult male and female Sprague-Dawley rats that were exposed to either cocaine (50 mg/kg/day sc) or distilled water during infancy (postnatal days 11-20). Learning and memory were assessed at 4 months using the eight-arm radial maze. Training was carried out in three phases in order to separate procedural learning from spatial capacity. Once criterion (entering at least seven arms without repeating arms for four out of five trials) was achieved in the first training room (Room 1), testing was moved to a second room (Room 2) with unique visual cues and an identical maze. Upon reaching criterion in Room 2, animals were returned to Room 1 and examined again. Cocaine-pretreated rats were less accurate than vehicle-pretreated rats during the first 10 trials of training. During the first five trials in Room 2 cocaine-pretreated animals made more errors, and made errors earlier within trials, than the vehicle-pretreated animals. Upon return to Room 1, reliable Gender x Pretreatment interactions were found for errors and total arms entered. These data demonstrate that a brief period of postnatal cocaine exposure can impair spatial cognition in adulthood and tentatively suggest that females are more sensitive than males.

Behavioral responses to dopamine agonists in adult rats exposed to cocaine during the preweaning period.

In order to determine whether developmental cocaine exposure altered the functional responses of dopamine systems, the behavioral responses to selective D1 or D2/D3 agonists were examined and compared to rats treated during the same period with a selective inhibitor of the dopamine transporter, GBR 12909. Sprague-Dawley rats were administered cocaine or GBR 12909 at 25 or 50 mg/kg/day during postnatal days (PND) 11-20. At 60+ days of age, rats were administered a challenge drug (either SKF 82958, a full D1 agonist, at 1.0 or 10 mg/kg, or quinpirole, a D2/D3 agonist, at 0.08 or 0.5 mg/kg, or saline) and subjected to 1 h of behavioral assessment. The cocaine or GBR treatments produced significant effects in three behavioral categories: distance traveled, sniffing, and rearing. For distance traveled, preweaning treatments interacted with sex since in the males, all cocaine- and GBR-treated groups showed relatively flat patterns of locomotor activity across time blocks, while in the treated females, locomotor activity typically increased across the time blocks. For other behaviors, the treatments generally produced enhanced responses to the challenge drugs. These results suggest that intermittent inhibition of the dopamine transporter with either cocaine or GBR during PND 11-20 produces long-term alterations in the functional responses of dopaminergic systems but that the neural substrates for these effects depend upon the sex of the animal.

Sexual dimorphism in the brain metabolic response to prenatal cocaine exposure.

The effects of prenatal cocaine exposure on the metabolic function of major central neuronal systems in the periweanling rat are reported in this study. Pregnant Sprague--Dawley rats were administered cocaine at either 30 or 60 mg/kg or the vehicle from gestation day (G) 8 through 22 via daily gastric intubation. Since prenatal cocaine has been shown to alter behavior in weanling rats, brain functional activity was quantified using the deoxyglucose method in male and female 21-day-old offspring (one of each gender/litter). Cocaine's effects were most significant within the limbic system where a three-way interaction between cocaine treatment, sex and brain region was seen. Within the limbic system, two regions, the rostral accumbens and the diagonal band of Broca showed reductions in metabolic activity in the exposed male offspring compared to the control offspring while no changes were seen in females. At more caudal levels of the forebrain, the accumbens (at the level of 1.2 micro rostral to Bregma) and septum showed cocaine-induced reductions in metabolism which were not dependent upon the sex of the animal. Metabolism within the hypothalamus also tended to show a significant interaction between treatment, gender and brain region (P=0.06). Two regions, including the ventromedial nucleus and lateral hypothalamic area, were metabolically depressed in the males alone while three other regions; the dorsomedial, arcuate, and medial preoptic nuclei were also metabolically depressed in the treated groups collapsed across gender. There were no significant treatment or sex-related effects or interactions within the sensory and motor systems. Chronic prenatal cocaine exposure reduced metabolism significantly in a restricted portion of the forebrain, the mesocortical-limbic system, particularly in regions associated with the medial forebrain bundle. These reductions were seen primarily in males while some regions showed changes which were independent of the sex of the animal. These cocaine-induced effects resembled, to a great extent, those seen in similarly-treated males examined as adults. The data emphasize that cocaine use during a restricted period of early pregnancy depresses function within limbic and hypothalamic regions and that many of these effects are sexually dimorphic in nature.

Differential behavioral responses to chronic amphetamine in adult male and female rats exposed to postnatal cocaine treatment.

The impact of cocaine exposure during development on behavioral sensitization as measured by locomotor activity and stereotypy following repeated intermittent administration of amphetamine is examined. Male and female Sprague-Dawley rats were exposed to cocaine at 50 mg/kg/day during postnatal days (PND) 11-20 and, as adults (PND193-212), were administered seven daily injections of 2.0 mg/kg amphetamine. Both locomotor activity and stereotypic behavior were assessed following the first and seventh injections. Control males and females showed sensitized behavior following repeated amphetamine injections with females showing greater locomotion while males showed increased stereotypy. Male rats pretreated with cocaine failed to develop sensitized locomotor or stereotypic responses following repeated amphetamine injections consistent with dampened D(1) receptor activity. Females pretreated with cocaine did not show a sensitized locomotor response but did display sensitization of stereotypy following repeated amphetamine administration. Thus, it appears that postnatal cocaine treatment produces differential effects on the circuits mediating sensitization behavior in male and female rats.

Orthodontic treatment for an adolescent with a history of acute lymphoblastic leukemia.

This case report describes the treatment of a Class I malocclusion that involved ectopic position of the maxillary permanent left canine and the mandibular permanent right second molar. The patient was an adolescent who presented with a medical history that was remarkable for diagnosis and treatment of acute lymphoblastic leukemia (ALL). Dental history was remarkable for significant, generalized shortened roots that were more severe in the mandibular arch. The treatment included fixed appliance therapy in the maxillary arch only and surgical luxation of the mandibular second molar. Successful integration of the maxillary permanent left canine was accomplished without excessive flaring of the maxillary permanent incisors or disruption of the buccal segment occlusion. The risk of external root resorption on teeth with abnormal root morphology, as a result of fixed appliance therapy, should be weighed against the relative benefits that are expected from treatment.

Neurobehavioral effects of perinatal AZT exposure in Sprague-Dawley weaning rats.

Because AZT (azidothymidine, zidovudine, ZDV) has become the standard of care for preventing HIV transmission during pregnancy, we conducted a study to assess the possible neurobehavioral effects of this drug, using a rat model. Each litter was randomly assigned to a treatment group: vehicle, AZT 50, 100, or 150 mg/kg, or no treatment. Treatments were administered once daily via gastric intubation, prenatally from gestation day (G) 19-22 and then postnatally from postnatal day (PND) 2-20, except the nontreated group, which was only weighed every 4 days. On PND21 each rat was given a single dose of amphetamine (0.25, 0.50, 0.75, or 1.0 mg/kg) or saline and placed in the Accuscan activity chamber for 1 h of data collection and video taping. Results show that all of the behaviors analyzed produced statistically significant main effects of perinatal treatment, challenge drug, and time block. For distance traveled, there was a significant three-way interaction between treatment, sex, and time block, an effect that was independent of the effects of handling and injecting the rats. That is, within the males, the AZT 150 group displayed the greatest amount of locomotion, while among the females, the AZT 50 group was the most active. Furthermore, the AZT 50 group showed significantly less margin time (wall hugging) and more grooming than the nontreated control group. However, handling contributed to these differences because they were not observed when the vehicle-intubated group was used as the control. Across all treatment groups, amphetamine increased locomotion, the duration of rearing, and sniffing, while it decreased wall hugging, grooming, and time spent quiet. Complex interactions between amphetamine dose and time block were also seen for each behavior. In summary, these data indicate that amphetamine, at the doses used in the current study, alters behavior in the rat at 21 days of age, and that perinatal AZT exposure alters behavior in a single domain, locomotion with the threshold for this effect depending on genders.

Cocaine decreases uteroplacental blood flow in the rat.

Although cocaine administration reduces blood flow to the fetus in the pregnant ewe, the effects of cocaine on uterine and placental blood flow in the pregnant rat have not been adequately documented. The current study tested the hypothesis that cocaine decreased uterine and placental blood flow in awake and freely moving pregnant rats 17 min following gastric intubation. Blood flow was determined using [14C]iodoantipyrine in pregnant Sprague-Dawley rats 1 day prior to parturition. On the day of the experiment, rats were intubated with either 60 mg/kg cocaine or the vehicle and 17 min later infused i.v. with 75 microCi [14C]iodoantipyrine. Ten arterial blood samples were taken over 1 min through a femoral arterial catheter placed on the previous day. At 1 min the animal was decapitated and the entire uterus rapidly removed and frozen. After processing for autoradiography, the amounts of radioactivity in the tissues were determined by computerized image analysis. The results show that cocaine reduced blood flow in the uterus by 27% and decreased blood flow in the placenta by 30%. While cocaine reduced the total amount of iodoantipyrine reaching the fetus, the distribution of tracer within the fetus did not appear to be altered by cocaine. Maternal blood pressure and heart rate decreased by 5% and 13% respectively (paired t-test), while maternal and fetal blood gases were not altered. These data indicate that acute cocaine administration reduces uteroplacental blood flow in the rat. The duration of this effect and whether these decreases are sufficient to produce neurobehavioral changes in the offspring remain to be determined.

Neurobehavioral effects of perinatal AZT exposure in Sprague-Dawley adult rats.

Since AZT (azidothymidine, zidovudine, ZDV) has become the standard of care for preventing human immunodeficiency virus transmission during pregnancy, we conducted a study to assess the possible long-term neurobehavioral effects of AZT, using a rat model. Each litter was randomly assigned to a treatment group: no treatment, vehicle or AZT 50, 100, or 150 mg/kg. Treatments were administered once daily via gastric intubation, prenatally from gestation day (G) 19-22 and then from postnatal day (PND) 2-20. Between PND 59-65, each rat was given a single dose of amphetamine (0.1, 0.5, 1.0, or 2.0 mg/kg) or saline and placed in the Accuscan activity chamber for 1 h of data collection and video taping. There was a significant interaction between perinatal treatment and amphetamine challenge drug for one behavioral category, distance traveled, which was due to differences in the nontreated control group compared to all treated groups. These data indicate that chronic AZT treatment at three dose levels during the perinatal period produces no lasting changes in response to amphetamine in the open field in the rat.