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Biomedical subjects

M M Adams

Publications and source records attributed to M M Adams.

At least 19 recordsLinked to original sources

Long-term body-weight-supported treadmill training and subsequent follow-up in persons with chronic SCI: effects on functional walking ability and measures of subjective well-being.

STUDY DESIGN: Longitudinal, prospective within-subject design. OBJECTIVES: (1) To determine the effects of long-term body-weight-supported treadmill training (BWSTT) on functional walking ability and perceived quality of life in persons with chronic incomplete spinal cord injury (SCI), and (2) to investigate whether training adaptations are maintained following cessation of the BWSTT programme. SETTING: Hamilton, Ontario, Canada. METHODS: A group of 14 individuals with chronic (mean 7.4 years postinjury) incomplete SCI (ASIA B & C) participated in thrice-weekly sessions of BWSTT for a period of approximately 12 months (144 sessions). Functional walking ability and indices of subjective well-being were evaluated during the training programme and over an 8-month follow-up. RESULTS: In total, 13 subjects successfully completed the 144 training sessions in the required study period (max. 15 months). Adherence to the thrice-weekly training frequency was 78.8%. All subjects improved in treadmill walking ability (54% reduction in required external body-weight support (BWS), 180% increase in treadmill walking speed, 335% increase in distance walked/session), and six subjects improved their capacity to walk over ground. There were accompanying increases in satisfaction with life and satisfaction with physical function, both of which were significantly correlated with improvements in treadmill walking ability. All but one subject returned for follow-up assessment 8 months post-training; while there was a slight decline in treadmill walking performance, over ground walking scores remained relatively stable. The only change in subjective well-being in the follow-up was a slight decrease in satisfaction with physical function. CONCLUSION: Thrice-weekly BWSTT for 12 months was an effective stimulus to improve treadmill walking ability and indices of subjective well-being in persons with chronic incomplete SCI, and most of these improvements were maintained for up to 8 months following the cessation of training.

Activities of Daily Living↗

Spasticity after spinal cord injury.

Symptoms of spasticity are often experienced by individuals with spinal cord injury (SCI) following a period of spinal shock and, in many cases, these symptoms negatively affect quality of life. Despite its prevalence, spasticity as a syndrome in the SCI population is not always managed effectively. This is likely due to the fact that the syndrome can have various presentations, each with their own specific etiology. This overview summarizes the symptoms and pathophysiology of the various presentations of spasticity in the SCI population and discusses the currently accepted management techniques. There is a need for a better understanding of the syndrome of spasticity as well as the development of a valid and reliable assessment tool.

Baclofen↗

Different modes of hippocampal plasticity in response to estrogen in young and aged female rats.

Estrogen regulates hippocampal dendritic spine density and synapse number in an N-methyl-D-aspartate (NMDA) receptor-dependent manner, and these effects may be of particular importance in the context of age-related changes in endocrine status. We investigated estrogen's effects on axospinous synapse density and the synaptic distribution of the NMDA receptor subunit, NR1, within the context of aging. Although estrogen induced an increase in axospinous synapse density in young animals, it did not alter the synaptic representation of NR1, in that the amount of NR1 per synapse was equivalent across groups. Estrogen replacement in aged female rats failed to increase axospinous synapse density; however, estrogen up-regulated synaptic NR1 compared with aged animals with no estrogen. Therefore, the young and aged hippocampi react differently to estrogen replacement, with the aged animals unable to mount a plasticity response generating additional synapses, yet responsive to estrogen with respect to additional NMDA receptor content per synapse. These findings have important implications for estrogen replacement therapy in the context of aging.

Aging↗

Hippocampal dependent learning ability correlates with N-methyl-D-aspartate (NMDA) receptor levels in CA3 neurons of young and aged rats.

Hippocampal N-methyl-D-Aspartate (NMDA) receptors mediate mechanisms of cellular plasticity critical for spatial learning in rats. The present study examined the relationship between spatial learning and NMDA receptor expression in discrete neuronal populations, as well as the degree to which putative age-related changes in NMDA receptors are coupled to the effects of normal aging on spatial learning. Young and aged Long-Evans rats were tested in a Morris water maze task that depends on the integrity of the hippocampus. Levels of NR1, the obligatory subunit for a functional NMDA receptor, were subsequently quantified both biochemically by Western blot in whole homogenized hippocampus, and immunocytochemically by using a high-resolution confocal laser scanning microscopy method. The latter approach allowed comprehensive, regional analysis of discrete elements of excitatory hippocampal circuitry. Neither method revealed global changes, nor were there region-specific differences in hippocampal NR1 levels between young and aged animals. However, across all subjects, individual differences in spatial learning ability correlated with NR1 immunofluorescence levels selectively in CA3 neurons of the hippocampus. Parallel confocal microscopic analysis of the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) receptor failed to reveal reliable differences as a function of age or spatial learning ability. This analysis linking age, performance, and NR1 levels demonstrates that although dendritic NR1 is generally preserved in the aged rat hippocampus, levels of this receptor subunit in selective elements of hippocampal circuitry are linked to spatial learning. These findings suggest that NMDA receptor abundance in CA3 bears a critical relationship to learning mediated by the hippocampus throughout the life span.

Age Factors↗

N-methyl-D-aspartate receptor mRNA levels change during reproductive senescence in the hippocampus of female rats.

Estrogen interacts with N-methyl-d-aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In the hippocampus, estrogens increase both dendritic spine density and synapse number, and NMDA antagonists block these effects. This plasticity in the hippocampus mediated by estrogen may be of particular importance in the context of aging when estrogen levels change and cognitive function is often impaired. Therefore, the present study was designed to investigate effects of aging and reproductive status on NMDA receptor (NR) subunit mRNA levels in the hippocampus. NR1, NR2A, and NR2B mRNA levels were measured by RNase protection assay in young (3-4 month), middle-aged (12-13 month), and aged (24-25 month) Sprague-Dawley rats in different phases of the estrous cycle in cycling animals and in acyclic subjects. Our results demonstrated that NMDA receptor subunit mRNA levels were much more prominently affected by the chronological age than by the reproductive status of the animals. Age-related changes were observed in NR1, NR2A, and NR2B in the ventral hippocampus and in NR1 and NR2B in the dorsal hippocampus. However, the only relationship with reproductive status was seen for NR1 mRNA, and this was restricted to the ventral hippocampus. An interaction between chronological age and reproductive status was found, with higher levels of NR1 mRNA seen in young animals in proestrus than in those in diestrus I (high and low estrogen levels, respectively). However, this relationship was not seen in the aged subjects. These results demonstrate that the hippocampus is subjected to age-related alterations in NMDA receptor subunit mRNA levels and that animals of different ages are influenced differently by reproductive status. This shift in the NMDA receptor mRNA levels may be a possible molecular mechanism contributing to alterations in cognitive behavior during normal aging.

Aging↗

Length of postovariectomy interval and age, but not estrogen replacement, regulate N-methyl-D-aspartate receptor mRNA levels in the hippocampus of female rats.

Estrogens and N-methyl-D-aspartate (NMDA) receptors regulate multiple aspects of morphological and functional plasticity in young animals. For example, estrogens increase spine density in the hippocampus, and NMDA antagonists block these effects. Few studies have examined the effects of age, postovariectomy interval, and duration of estrogen replacement in the hippocampus and more specifically on NMDA receptor subunits. Therefore, the present study was designed to investigate the effects of short- and long-term estrogen replacement or deprivation on mRNA levels of three NMDA receptor subunits, NR1, NR2A, and NR2B, in the hippocampus of aging female Sprague-Dawley rats. Young (3- to 4-month-old) and middle-aged (12- to 13-month-old) rats were ovariectomized for 1 month and then treated with estrogen or vehicle for either 2 days or 2 weeks. Another set of middle-aged and aged (24-to 25-month-old) animals were ovariectomized for 6 months and treated with estrogen or vehicle for 2 days or 2 weeks. RNase protection assay was used to assess changes in the NMDA receptor subunit mRNA levels. Our results demonstrated significant effects of age and length of ovariectomy on NMDA receptor mRNA levels, with little effect of the estrogen status of the animals on these parameters. The largest effect was seen for the length of the postovariectomy interval, with the results demonstrating that rats with a short-term ovariectomy have substantially higher NMDA receptor subunit mRNA levels than animals with long-term ovariectomy. The most dramatic effects of aging were seen for NR1 and NR2B mRNAs in ventral hippocampus, with large age-related increases. These data suggest that age and duration of ovariectomy impact NMDA receptor mRNA levels in the hippocampus, potentially affecting the stoichiometry and/or function of these receptors. These findings have important implications for postmenopausal or hysterectomy/oophorectomy estrogen depletion and replacement in humans.

Aging↗

Attenuated lesion-induced N-methyl-D-aspartate receptor (NMDAR) plasticity in the dentate gyrus of aged rats following perforant path lesions.

Young animals demonstrate a significant upregulation of N-methyl-d-aspartate receptor 1 (NMDAR1) in the outer molecular layer (OML) of the dentate gyrus following a total unilateral ablation of the perforant path, and this response presumably facilitates a degree of functional recovery. Aged animals have attenuated responses to lesion-induced synaptic plasticity as compared with young subjects, and in fact display decreased synaptogenesis and sprouting following a unilateral perforant path lesion. To investigate the response of NMDAR1 in the dentate gyrus of aged animals to perforant path ablation, 24-month-old Sprague-Dawley male rats received a unilateral knife cut of the angular bundle. Our results demonstrated that aged animals displayed a blunted response to lesion-induced NMDA receptor-mediated plasticity, suggesting that aged animals have an impaired ability to respond to deafferentation through an increase in NMDA receptor levels in the deafferented zone.

Age Factors↗

Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats.

The present study examined the long-standing concept that changes in hippocampal circuitry contribute to age-related learning impairment. Individual differences in spatial learning were documented in young and aged Long-Evans rats by using a hippocampal-dependent version of the Morris water maze. Postmortem analysis used a confocal laser-scanning microscopy method to quantify changes in immunofluorescence staining for the presynaptic vesicle glycoprotein, synaptophysin (SYN), in the principal relays of hippocampal circuitry. Comparisons based on chronological age alone failed to reveal a reliable difference in the intensity of SYN staining in any region that was examined. In contrast, aged subjects with spatial learning deficits displayed significant reductions in SYN immunoreactivity in CA3 lacunosum-moleculare (LM) relative to either young controls or age-matched rats with preserved learning. SYN intensity values for the latter groups were indistinguishable. In addition, individual differences in spatial learning capacity among the aged rats correlated with levels of SYN staining selectively in three regions: outer and middle portions of the dentate gyrus molecular layer and CA3-LM. The cross-sectional area of SYN labeling, by comparison, was not reliably affected in relation cognitive status. These findings are the first to demonstrate that a circuit-specific pattern of variability in the connectional organization of the hippocampus is coupled to individual differences in the cognitive outcome of normal aging. The regional specificity of these effects suggests that a decline in the fidelity of input to the hippocampus from the entorhinal cortex may play a critical role.

Aging↗

Visual cortical projections and chemoarchitecture of macaque monkey pulvinar.

We investigated the patterns of projections from the pulvinar to visual areas V1, V2, V4, and MT, and their relationships to pulvinar subdivisions based on patterns of calbindin (CB) immunostaining and estimates of visual field maps (P(1), P(2) and P(3)). Multiple retrograde tracers were placed into V1, V2, V4, and/or MT in 11 adult macaque monkeys. The inferior pulvinar (PI) was subdivided into medial (PI(M)), posterior (PI(P)), central medial (PI(CM)), and central lateral (PI(CL)) regions, confirming earlier CB studies. The P(1) map includes PI(CL) and the ventromedial portion of the lateral pulvinar (PL), P(2) is found in ventrolateral PL, and P(3) includes PI(P), PI(M), and PI(CM). Projections to areas V1 and V2 were found to be overlapping in P(1) and P(2), but those from P(2) to V2 were denser than those to V1. V2 also received light projections from PI(CM) and, less reliably, from PI(M). Neurons projecting to V4 and MT were more abundant than those projecting to V1 and V2. Those projecting to V4 were observed in P(1), densely in P(2), and also in PI(CM) and PI(P) of P(3). Those projecting to MT were found in P(1)- P(3), with the heaviest projection from P(3). Projections from P(3) to MT and V4 were mainly interdigitated, with the densest to MT arising from PI(M) and the densest to V4 arising from PI(P) and PI(CM). Because the calbindin-rich and -poor regions of P(3) corresponded to differential patterns of cortical connectivity, the results suggest that CB may further delineate functional subdivisions in the pulvinar.

Animals↗

A comparative analysis of huddling in infant Norway rats and Syrian golden hamsters: does endothermy modulate behavior?

In infant rats, huddling improves surface-to-volume ratios and provides metabolic savings during cold exposure. It is unclear, however, whether endothermy is also a necessary component of huddling. In the present experiment, huddles composed of infant Norway rats (2- or 8-day-olds), which produce heat endogenously, or Syrian golden hamsters (8-day-olds), which do not produce heat endogenously, were exposed to decreases in air temperature. Behavioral and physiological responses were monitored throughout the test. Rats, especially at 8 days of age, were better able to thermoregulate using huddling than hamsters, due in part to endogenous heat production. Furthermore, 8-day-old rats exhibited behavioral responses that promote heat retention, suggesting that both physiological and behavioral mechanisms contribute to effective thermoregulation during huddling in the cold.

Adipose Tissue, Brown↗

Does inadequate prenatal care contribute to growth retardation among second-born African-American babies?

The authors evaluated the relation between adequacy of prenatal care and risk of delivery of full term small-for-gestational-age (SGA) infants. Data were derived from maternally linked birth certificates for 6,325 African-American women whose first two pregnancies ended in singleton, full term live births in Georgia from 1989 through 1992. The authors used stratified analysis to assess the effect of prenatal care on the risk of having an SGA baby in the second pregnancy among women with and without an SGA baby in their first pregnancy. The group of women with a history of SGA birth may be more likely to include persons for whom SGA delivery is related to factors, such as genetics, that are not amenable to intervention by prenatal care. Inadequate prenatal care was not associated with the risk of SGA delivery among women who had previously delivered an SGA baby. In unadjusted analyses, inadequate prenatal care was associated with an increased risk of delivering a full term SGA baby in the second pregnancy among women whose first baby was not SGA (risk ratio = 1.28; 95% confidence interval: 1.05, 1.55). The association did not persist when data were adjusted for confounding variables (odds ratio = 1.11; 95% confidence interval: 0.89, 1.38). Regardless of outcome in the first pregnancy, adequate prenatal care did not reduce the risk of full term SGA birth among second pregnancies in this population.

Adolescent↗

Perinatal changes in hypothalamic N-methyl-D-aspartate receptors and their relationship to gonadotropin-releasing hormone neurons.

During the neonatal period, the brain is subject to profound alterations in neuronal circuitry due to high levels of synaptogenesis and gliogenesis. In neuroendocrine regions such as the preoptic area-anterior hypothalamus (POA-AH), the site of GnRH perikarya, these changes could affect the maturation of GnRH neurons. Because the GnRH system is developmentally regulated by glutamatergic neurons, we hypothesized that changes in the N-methyl-D-aspartate (NMDA) receptor system begin early in postnatal development, before the onset of puberty, thereby playing a role in establishing the appropriate environment for the subsequent maturation of GnRH neurons. To this end, we determined developmental changes in NMDA receptors, alterations in GnRH gene expression, and the regulation of GnRH neurons by the NMDA receptor system in developing male and female rats. In Exp I, NMDA receptor subunit (NR) 1 mRNA levels in the POA-AH were found to increase significantly (approximately 5-fold) from E18 through P10 in both males and females. NR2b mRNA increased significantly between P0 and P5 in both males and females. In contrast, NR2a subunit mRNA, which was in very low abundance in both males and females, increased only in males between P10 and P15. In Exp II we determined that GnRH gene expression changes differentially in developing male and female rats, with increases from P0 to P5 in males, and decreases from P5 to P10 in females. This latter effect in females is attributed to a change in GnRH gene transcription because GnRH primary transcript RNA levels paralleled changes in GnRH mRNA levels. In Exp III, we tested effects of treatment with an NMDA receptor analog on GnRH mRNA levels and found that only P5 and P10 male rats responded to NMDA receptor activation with an increase in GnRH mRNA levels, via a posttranscriptional mechanism. This greater responsiveness of males to NMDA receptor stimulation may be due to differences in the composition and levels of NMDA receptor subunits. Exp IV examined the localization of NR1 in the POA-AH during neonatal development. No GnRH neurons were immunopositive for NR1, indicating that effects of glutamate on GnRH neurons are mediated by interneurons or other glutamate receptor subunits or types. Taken together, these data indicate that glutamatergic inputs to the POA-AH change dramatically during the early postnatal period, before puberty and before the GnRH system is fully responsive to glutamate, consistent with the hypothesis that the maturation of inputs to GnRH neurons, and the establishment of the proper neurotransmitter "milieu" enabling the activation of GnRH neurons, occurs before the onset of puberty.

Animals↗

More awakenings and heart rate variability during supine sleep in preterm infants.

OBJECTIVE: The Task Force of The American Academy of Pediatrics (1996) recommends the nonprone sleeping position for asymptomatic preterm infants to prevent sudden infant death syndrome. The mechanism by which the nonprone sleeping position reduces the rate of sudden infant death syndrome is unclear for full-term infants and the precise effect of sleeping position on sleep and cardiorespiratory characteristics has never been addressed in preterm infants. The purpose of the present study was to clarify the effect of sleeping position on sleep and cardiorespiratory characteristics in preterm infants at an age when they are ready for discharge. STUDY DESIGN: Sixteen asymptomatic preterm infants were studied in both supine and prone sleeping positions at 36.5 +/- 0.6 weeks' postconceptional age using videosomnography. Sleep, respiratory, and heart rate characteristics were compared between the two positions using each infant as his/her own control. RESULTS: More awakenings (ie, arousals >/=60 seconds) were seen during all sleep states in the supine sleeping position but overall the total sleep and percent sleep state were not affected by sleeping position. After each feeding, the first quiet sleep was significantly shorter, with more heart rate variability and awakenings in the supine position. There were no significant differences in the occurrence of arousals (<60 seconds) or the incidence or severity of apnea and periodic breathing. No clinically significant apnea (>/=15 seconds), bradycardia, or oxygen desaturations were seen. CONCLUSION: In 36-week-postconceptional age preterm infants, the supine sleeping position had less quiet sleep and was associated with greater heart rate variability during the first sleep cycle after the feeding. More awakenings were seen during all sleep states in the supine position. These data support the American Academy of Pediatrics recommendation for "Back to Sleep" for asymptomatic preterm infants because more awakenings and lower threshold for arousal may provide some benefit for the infant responding to a life-threatening event. However, further studies are needed to address positional effect on the physiologic measures in preterm infants at older ages (later stages of development). Precisely what constitutes the most healthy or advantageous sleep for newborn infants remains an important question.

Arousal↗

Completeness of ascertainment of prenatal smoking using birth certificates and confidential questionnaires: variations by maternal attributes and infant birth weight. PRAMS Working Group. Pregnancy Risk Assessment Monitoring System.

Birth certificate data frequently are used to monitor the prevalence of smoking during pregnancy. The authors used a two-sample capture-recapture method to estimate the completeness of ascertainment of prenatal smoking on birth certificates and on confidential questionnaires in six US states. Completeness of ascertainment was also examined according to maternal attributes and infant birth weight. The samples included white women who delivered a live infant between 1993 and 1995 in one of six states (Alabama, Alaska, Georgia, Maine, South Carolina, or West Virginia) and who responded to a questionnaire mailed to them 2-6 months postpartum as part of the Pregnancy Risk Assessment Monitoring System. State-specific sample sizes ranged from 2,647 to 4,795. The completeness of ascertainment ranged from 70.6% to 82.0% using birth certificates and from 86.2% to 90.3% using confidential questionnaires. In all six states, the birth certificates' completeness of ascertainment varied by maternal education and infant birth weight, and the questionnaires' completeness varied by maternal age. Both birth certificates and questionnaires underestimated the true extent of smoking during pregnancy among these white women. Differential reporting by birth weights recorded on birth certificates would result in an overestimated association between low birth weight and prenatal smoking.

Adolescent↗

Are we underestimating rates of vaginal birth after previous cesarean birth? The validity of delivery methods from birth certificates.

Previous studies of birth certificates have not fully evaluated how accurately they identify delivery methods that have a historical component, such as repeat cesarean and vaginal birth after previous cesarean (VBAC). The authors used linked Georgia birth certificates for first and second deliveries to examine the accuracy of four reported delivery methods in the second pregnancy: vaginal (without previous cesarean), VBAC, primary cesarean, and repeat cesarean, as well as an indicator of a previous cesarean. From the immediate birth certificates, the delivery method for each of the two births was classified as vaginal (V) or cesarean section (CS), which produced possible sequences of V-V, CS-V, V-CS, and CS-CS. The delivery method for the second births to 106,049 women from 1989 through 1992 was reviewed, taking into account the historical information from the linked certificates regarding the first births. Only 42.0% of women with a CS-V sequence were correctly designated on the second birth certificate as a VBAC; 79.3% of women with a V- CS sequence were correctly designated as primary cesarean. From 1980 through 1988, birth certificates contained a check box indicating a previous cesarean (but no VBAC box). During this period, only 75.5% of 25,491 women with a previous cesarean were so designated on the birth certificate. These findings suggest that cross-sectional vital records data substantially underestimate VBAC and primary cesarean rates.

Birth Certificates↗

The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex.

Behavioral and neurophysiological studies suggest that skill learning can be mediated by discrete, experience-driven changes within specific neural representations subserving the performance of the trained task. We have shown that a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training. These gains did not generalize to the contralateral hand nor to a matched sequence of identical component movements, suggesting that a lateralized representation of the learned sequence of movements evolved through practice. This interpretation was supported by functional MRI data showing that a more extensive representation of the trained sequence emerged in primary motor cortex after 3 weeks of training. The imaging data, however, also indicated important changes occurring in primary motor cortex during the initial scanning sessions, which we proposed may reflect the setting up of a task-specific motor processing routine. Here we provide behavioral and functional MRI data on experience-dependent changes induced by a limited amount of repetitions within the first imaging session. We show that this limited training experience can be sufficient to trigger performance gains that require time to become evident. We propose that skilled motor performance is acquired in several stages: "fast" learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration, and then "slow" learning, consisting of delayed, incremental gains in performance emerging after continued practice. This time course may reflect basic mechanisms of neuronal plasticity in the adult brain that subserve the acquisition and retention of many different skills.

Adult↗

Live births resulting from unintended pregnancies: an evaluation of synthetic state-based estimates.

OBJECTIVES: Most states lack information on the proportion of live births resulting from unintended pregnancies. We evaluated a potential solution to the lack of data, a synthetic state-based estimate of the percentage of live births resulting from unintended pregnancies for the state of Georgia. METHODS: We constructed the synthetic estimate by standardizing the 1995 National Survey of Family Growth data by the race, marital status, and age distribution of Georgia residents ages 15-44 years who delivered a live birth during 1990-1994. Two surveys conducted in Georgia during the same period that collected information on unintended pregnancies were used for comparison: the Georgia Women's Health Survey (GWHS) and the Georgia Pregnancy Risk Assessment Monitoring System (PRAMS). RESULTS: The synthetic estimate (35.2%, 95% CI = 33.5%-36.7%) was not statistically different from the GWHS estimate (39.6%, 95% CI = 35.7%-43.5%), but was significantly lower than the Georgia PRAMS estimate (49.0%, 95% CI = 45.5%-52.5%). When we stratified by race, marital status, and age, the synthetic and GWHS estimates were statistically similar except for married females and females ages 25-34 years, for whom the synthetic estimates were lower. For all groups of females, the synthetic estimates were statistically lower than the Georgia PRAMS estimates. CONCLUSIONS: The synthetic estimate can be a useful method for states that need to know the overall magnitude of the percentage of live births resulting from unintended pregnancy for purposes such as program planning.

Adolescent↗