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Biomedical subjects

L Atkinson

Publications and source records attributed to L Atkinson.

At least 19 recordsLinked to original sources
PubMed2004

Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS.

Presynaptic P2X(7) receptors are thought to play a role in the modulation of transmitter release and have been localised to terminals with the location and morphology typical of excitatory boutons. To test the hypothesis that this receptor is preferentially associated with excitatory terminals we combined immunohistochemistry for the P2X(7) receptor subunit (P2X(7)R) with that for two vesicular glutamate transporters (VGLUT1 and VGLUT2) in the rat CNS. This confirmed that P2X(7)R immunoreactivity (IR) is present in glutamatergic terminals; however, whether it was co-localised with VGLUT1-IR or VGLUT2-IR depended on the CNS region examined. In the spinal cord, P2X(7)R-IR co-localised with VGLUT2-IR. In the brainstem, co-localisation of P2X(7)R-IR with VGLUT2-IR was widespread, but co-localisation with VGLUT1-IR was seen only in the external cuneate nucleus and spinocerebellar tract region of the ventral medulla. In the cerebellum, P2X(7)R-IR co-localised with both VGLUT1 and VGLUT2-IR in the granular layer. In the hippocampus it was co-localised only with VGLUT1-IR, including in the polymorphic layer of the dentate gyrus and the substantia radiatum of the CA3 region. In other forebrain areas, P2X(7)R-IR co-localised with VGLUT1-IR throughout the amygdala, caudate putamen, striatum, reticular thalamic nucleus and cortex and with VGLUT2-IR in the dorsal lateral geniculate nucleus, amygdala and hypothalamus. Dual labelling studies performed using markers for cholinergic, monoaminergic, GABAergic and glycinergic terminals indicated that in certain brainstem and spinal cord nuclei the P2X(7)R is also expressed by subpopulations of cholinergic and GABAergic/glycinergic terminals. These data support our previous hypothesis that the P2X(7)R may play a role in modulating glutamate release in functionally different systems throughout the CNS but further suggest a role in modulating release of inhibitory transmitters in some regions.

Animals↗
PubMed2004

Association of potassium channel Kv3.4 subunits with pre- and post-synaptic structures in brainstem and spinal cord.

Voltage-gated K+ channels (Kv) are divided into eight subfamilies (Kv1-8) and play a major role in determining the excitability of neurones. Members of the Kv3 subfamily are highly abundant in the CNS, with each Kv3 gene (Kv3.1-Kv3.4) exhibiting a unique pattern of expression, although single neurones can express more than one subtype. Of the Kv3 subunits relatively little is known of the Kv3.4 subunit distribution in the nervous system, particularly in the brainstem and spinal cord of the rat. We performed immunohistochemistry to determine both the cellular and sub-cellular distribution of the Kv3.4 subunit in these areas. Kv3.4 subunit immunoreactivity (Kv3.4-IR) was widespread, with dense, punctate staining in many regions including the intermediolateral cell column (IML) and the dorsal vagal nucleus (DVN), nucleus ambiguus (NA) and nucleus tractus solitarius (NTS). In the ventral horn a presynaptic location was confirmed by co-localization of Kv3.4-IR with the synaptic vesicle protein, SV2 and also with the glutamate vesicle markers vesicular glutamate transporter (VGluT) 1, VGluT2 or the glycine transporter GlyT2, suggesting a role for the channel in both excitatory and inhibitory neurotransmission. Electron microscopy confirmed a presynaptic terminal location of Kv3.4-IR in the VH, IML, DVN, NA and NTS. Interestingly however, patches of Kv3.4-IR were also revealed postsynaptically in dendritic and somatic structures throughout these areas. This staining was striking due to its localization at synaptic junctions at terminals with morphological features consistent with excitatory functions, suggesting an association with the postsynaptic density. Therefore the pre and postsynaptic localization of Kv3.4-IR suggests a role both in the control of transmitter release and in regulating neuronal excitability.

Amino Acid Transport Systems, Neutral↗
PubMed2004

Formal versus informal interventions for challenging behaviour in persons with intellectual disabilities.

BACKGROUND: Although effective, humane treatments exist for persons with intellectual disabilities (ID) who have challenging behaviour, little research has examined the extent to which clients receive formal, documented vs. undocumented interventions. METHODS: Caregivers (of 625 persons with ID living in community and institutional residences in Ontario, Canada) were interviewed to examine the prevalence of different types of interventions. RESULTS: Overall, 55% of the 2506 different interventions (for 1464 target behaviours) were informal (i.e. lacking documented input from a professional, written intervention plans, and systematic evaluation). No significant differences emerged on formality of intervention across participant gender, age, level of ID, and type of residence. There were significantly more informal than formal behavioural interventions and counselling/psychotherapy, and no significant difference in the overall prevalence of formal and informal intrusive procedures. Behaviour control medications were paired more often with formal (67%) than informal interventions for dangerous behaviours. Formal interventions were associated with higher caregiver-reported estimates of behavioural improvement, higher inter-rater agreement on the descriptions of an individual client's target behaviours and interventions, and more caregiver training and supervision. CONCLUSIONS: The low levels of intervention accountability, training and supervision may place many clients with challenging behaviour at increased risk for ineffective and unnecessary restrictive interventions, and physical abuse. The results of this survey stimulated the government to write province-wide standards (that have yet to be implemented).

Adolescent↗
PubMed2003

Subcellular localization of neuronal nitric oxide synthase in the rat nucleus of the solitary tract in relation to vagal afferent inputs.

In the nucleus of the solitary tract (NTS), nitric oxide (NO) modulates neuronal circuits controlling autonomic functions. A proposed source of this NO is via nitric oxide synthase (NOS) present in vagal afferent fibre terminals, which convey visceral afferent information to the NTS. Here, we first determined with electron microscopy that neuronal NOS (nNOS) is present in both presynaptic and postsynaptic structures in the NTS. To examine the relationship of nNOS to vagal afferent fibres the anterograde tracer biotinylated dextran amine was injected into the nodose ganglion and detected in brainstem sections using peroxidase-based methods. nNOS was subsequently visualised using a pre-embedding immunogold procedure. Ultrastructural examination revealed nNOS immunoreactivity in dendrites receiving vagal afferent input. However, although nNOS-immunoreactive terminals were frequently evident in the NTS, none were vagal afferent in origin. Dual immunofluorescence also confirmed lack of co-localisation. Nevertheless, nNOS immunoreactivity was observed in vagal afferent neurone cell bodies of the nodose ganglion. To determine if these labelled cells in the nodose ganglion were indeed vagal afferent neurones nodose ganglion sections were immunostained following application of cholera toxin B subunit to the heart. Whilst some cardiac-innervating neurones were also nNOS immunoreactive, nNOS was never detected in the central terminals of these neurones. These data show that nNOS is present in the NTS in both pre- and postsynaptic structures. However, these presynaptic structures are unlikely to be of vagal afferent origin. The lack of nNOS in vagal afferent terminals in the NTS, yet the presence in some vagal afferent cell bodies, suggests it is selectively targeted to specific regions of the same neurones.

Animals↗
PubMed2003

Mastery motivation in young children with Down's syndrome: relations with cognitive and adaptive competence.

BACKGROUND: Prior research on relations between motivation and competence have focused on cognitive competence, despite theoretical predictions that mastery motivation spurs behaviour that is effective in meeting the demands of one's environment, i.e. adaptive competence. Issues of adaptive competence are especially relevant for children with developmental delay since functional independence is an important long-term goal for these children. METHODS: In the present study, mastery motivation was examined in relation to both cognitive and adaptive competence in 5-year-old children with Down's syndrome (n = 41). RESULTS: Scores on mastery task and parent-report measures of mastery motivation were generally low, but positively related to scores on standardized measures of cognitive competence and adaptive competence. CONCLUSIONS: This is the first study of motivation-competence relations in pre-school-age children. The findings have implications for both developmental theory and early intervention efforts, and the authors hope that they will serve as a stimulus for future research on cross-domain relationships in atypical populations.

Adaptation, Physiological↗
PubMed2001

Neuronal P2X7 receptors are targeted to presynaptic terminals in the central and peripheral nervous systems.

The ionotropic ATP receptor subunits P2X(1-6) receptors play important roles in synaptic transmission, yet the P2X(7) receptor has been reported as absent from neurons in the normal adult brain. Here we use RT-PCR to demonstrate that transcripts for the P2X(7) receptor are present in extracts from the medulla oblongata, spinal cord, and nodose ganglion. Using in situ hybridization mRNA encoding, the P2X(7) receptor was detected in numerous neurons throughout the medulla oblongata and spinal cord. Localizing the P2X(7) receptor protein with immunohistochemistry and electron microscopy revealed that it is targeted to presynaptic terminals in the CNS. Anterograde labeling of vagal afferent terminals before immunohistochemistry confirmed the presence of the receptor in excitatory terminals. Pharmacological activation of the receptor in spinal cord slices by addition of 2'- and 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP; 30 microm) resulted in glutamate mediated excitation of recorded neurons, blocked by P2X(7) receptor antagonists oxidized ATP (100 microm) and Brilliant Blue G (2 microm). At the neuromuscular junction (NMJ) immunohistochemistry revealed that the P2X(7) receptor was present in motor nerve terminals. Furthermore, motor nerve terminals loaded with the vital dye FM1-43 in isolated NMJ preparations destained after application of BzATP (30 microm). This BzATP evoked destaining is blocked by oxidized ATP (100 microm) and Brilliant Blue G (1 microm). This indicates that activation of the P2X(7) receptor promotes release of vesicular contents from presynaptic terminals. Such a widespread distribution and functional role suggests that the receptor may be involved in the fundamental regulation of synaptic transmission at the presynaptic site.

Animals↗
PubMed2001

Advances in neurotrauma in Australia 1970-2000.

The management of neurotrauma in Australia has been one of the significant public health triumphs during the last 30 years of the 20th century. State and national government agencies act in a coordinated fashion to collect data and to promote research or how to manage neurotrauma patients. Between 1970 and 1995, fatalities from road accidents decreased by 47%. Hospital admissions have decreased by 40% despite a 40% increase in the population and a 120% increase in registered vehicles. Fatalities per 10,000 registered vehicles were 8.05% in 1970 and they fell to 1.84% per vehicles in 1995, while fatalities per 10,000 population were 3 in 1970 falling to 1.11 in 1995. Hospitalization from road crashes decreased 23% between March 1988 and March 1997. Public education has steadily improved, backed by the state public health sources. A uniform code of road safety laws has been adopted, backed by legislation and legal penalties and increasing police enforcement. Clinical care of patients has improved as a result of faster communications, tele-medicine, trauma systems, the CT scanner, intensive care units, and improved monitoring. Patient rehabilitation and counseling are now carried out at units accredited by the Australian Council on Health Care Standards.

Australia↗
PubMed2001

Errorless compliance training with physically abusive mothers: a single-case approach.

OBJECTIVE: "Errorless compliance training" is a recently developed, success-based approach for teaching children to comply with parental requests without the use of coercive consequences. Two mothers were trained to use this intervention to reduce severe child defiance that was precipitating mother/child confrontations and physical abuse. METHOD: To determine probability of child compliance to specific requests, we observed mothers delivering requests to their child. We then developed a hierarchy of compliance probabilities for each child. Mothers were trained to deliver a high density of Level 1 requests (those that typically yielded compliance), and provide praise for child compliance. Lower probability request levels were introduced gradually, at a slow enough pace to preclude noncompliant responses, reducing the need for mothers to respond aversively to child behavior. RESULTS: At treatment completion and follow-up, both children demonstrated substantial improvements in compliance. CONCLUSIONS: The errorless approach may be well suited to managing parenting deficits and child opposition commonly associated with family violence.

Adult↗
PubMed2001

Comorbidity of psychiatric and substance use disorders in late adolescence: a cluster analytic approach.

Cluster analysis was used to identify subgroups of youths with past-year substance and/or psychiatric disorders (N = 110, mean age 19.0 years). Data for this study came from a community-based, prospective longitudinal investigation of speech/language (S/L) impaired children and matched controls who participated in extensive diagnostic and psychosocial assessments at entry into the study at 5 years of age and again at follow-up. Clustering variables were based on five DSM diagnostic categories assessed at age 19with the University of Michigan Composite International Diagnostic Interview. Using Ward's method, the five binary variables were entered into a hierarchical cluster analysis. An iterative clustering method (K-means) was then used to refine the Ward solution. Finally, a series of analyses of variance (ANOVAs) were run to analyze group differences between clusters on measures of Global Assessment of Functioning (GAF), criminal involvement, anxiety and depressive symptomatology, and frequency of drug use and heavy drinking. The analysis yielded eight replicable cluster groups, which were labeled as follows: (a) anxious (20.9%); (b) anxious drinkers (5.5%); (c) depressed (16.4%); (d) depressed drug abusers (10%); (e) antisocial (16.4%); (f) antisocial drinkers (10%); (g) drug abusers (8.2%); (h) problem drinkers (12.7%). These groups were differentiated by external criteria, thus supporting the validity of our cluster solution. Cluster membership was associated with a history of S/L impairment: A large proportion of the depressed drug abusers and the antisocial cluster group had S/L impairment that was identified at age 5. Clarification of the developmental progress of the youths in these cluster groups can inform our approach to early intervention and treatment.

Adolescent↗
PubMed2001

Fourteen-year follow-up of speech/language-impaired and control children: psychiatric outcome.

OBJECTIVE: To examine the association between early childhood speech and language disorders and young adult psychiatric disorders. METHOD: In a longitudinal community study conducted in the Ottawa-Carleton region of Ontario, Canada, interviewers administered structured psychiatric interviews to age 19 participants who were originally identified as speech-impaired only, language-impaired, or nonimpaired at age 5. The first stage of the study took place in 1982 when participants were 5 years old, and the latest stage of the study took place between 1995 and 1997 when participants had a mean age of 19 years. This report examines the association between early childhood speech/language status and young adult psychiatric outcome. RESULTS: Children with early language impairment had significantly higher rates of anxiety disorder in young adulthood compared with nonimpaired children. The majority of participants with anxiety disorders had a diagnosis of social phobia. Trends were found toward associations between language impairment and overall and antisocial personality disorder rates. Males from the language-impaired group had significantly higher rates of antisocial personality disorder compared with males from the control group. Age of onset and comorbidity did not differ by speech/language status. The majority of participants with a disorder had more than one. CONCLUSIONS: Results support the association between early childhood speech and language functioning and young adult psychiatric disorder over a 14-year period. This association underscores the importance of effective and early interventions.

Adult↗
PubMed2001

Child-parent attachment and children's peer relations: a quantitative review.

The central premise of attachment theory is that the security of the early child-parent bond is reflected in the child's interpersonal relationships across the life span. This meta-analysis was based on 63 studies that reported correlations between child-parent attachment and children's peer relations. The overall effect size (ES) for child-mother attachment was in the small-to-moderate range and was quite homogeneous. ESs were similar in studies that featured the Strange Situation and Q-sort methods. The effects were larger for peer relations in middle childhood and adolescence than for peer relations in early childhood. ESs were also higher for studies that focused on children's close friendships rather than on relations with other peers. Gender and cultural differences in ESs were minimal. The results for the few studies on father-child attachment were inconclusive.

Adolescent↗
PubMed2000

Attachment security: a meta-analysis of maternal mental health correlates.

This meta-analysis addresses the association between attachment security and each of three maternal mental health correlates. The meta-analysis is based on 35 studies, 39 samples, and 2,064 mother-child pairs. Social-marital support (r = .14; based on 16 studies involving 17 samples and 902 dyads), stress (r = .19; 13 studies, 14 samples, and 768 dyads), and depression (r = .18; 15 studies, 19 samples, and 953 dyads) each proved significantly related to attachment security. All constructs showed substantial variance in effect size. Ecological factors and approach to measuring support may explain the heterogeneity of effect sizes within the social-marital support literature. Effect sizes for stress varied according to the time between assessment of stress and assessment of attachment security. Among studies of depression, clinical samples yielded significantly larger effect sizes than community samples. We discuss these results in terms of measurement issues (specifically, overreliance on self-report inventories) and in terms of the need to study the correlates of change in attachment security, rather than just the correlates of attachment security per se.

Adult↗
PubMed2000

P2X(2) receptor immunoreactivity in the dorsal vagal complex and area postrema of the rat.

Adenosine 5'-triphosphate (ATP) can function as a fast synaptic transmitter through its actions on ionotropic (P2X) and metabotropic (P2Y) receptors in neuronal tissue. The ionotropic receptors have been classified into seven subtypes (P2X(1)-P2X(7)) by molecular cloning. However, they are difficult to distinguish pharmacologically owing to an absence of specific agonists and antagonists. In this study we used neuroanatomical methods to determine the origin and neurochemical phenotype of the P2X(2) subtype of purinoceptor in the dorsal medulla of the rat. Using immunohistochemistry we observed dense networks of P2X(2) receptor immunoreactive labelled fibres and terminals in the dorsal vagal complex and area postrema, as well as labelled cell bodies in the dorsal vagal nucleus and the area postrema. The P2X(2) receptor was localized presynaptically in vagal afferent fibres and terminals in the nucleus tractus solitarius at the ultrastructural level by combining injections of an anterograde tracer (biotin dextran amine) into the nodose ganglion with pre-embedding immunogold visualization of P2X(2) immunoreactivity. Terminals immunoreactive for the P2X(2) receptor in the nucleus tractus solitarius were found to contain glutamate, but not GABA immunoreactivity by post-embedding immunogold-labelling techniques. In cell bodies in the area postrema, dual immunofluorescence also indicated that P2X(2) receptor immunoreactive cells are glutamatergic but not GABAergic. The P2X(2) receptor was localized to vagal preganglionic neurons in the dorsal vagal nucleus that were identified by prior intraperitoneal injections of the retrograde tracer FluoroGold. No cells immunoreactive for the P2X(2) receptor were observed in the nucleus tractus solitarius. The localization of P2X(2) receptor immunoreactivity presynaptically in vagal afferent terminals indicates that the receptor may be involved in modulating transmitter release from vagal afferent fibres. Furthermore, the presence of the P2X(2) receptor in vagal preganglionic cells and in glutamatergic cells of the area postrema implies that it may, respectively, play a role in regulation of vagal efferent cell activity and modulation of excitatory outputs from the area postrema to other brain regions.

Animals↗
PubMed2000

Success-based, noncoercive treatment of oppositional behavior in children from violent homes.

OBJECTIVES: Errorless compliance training is a success-based, noncoercive intervention for children with severe oppositional behavior. The strategy involves hierarchical introduction of more demanding parental requests at a gradual pace that greatly reduces noncompliance and obviates the need for constraining consequences (e.g., time-out). In this study, this approach was evaluated as a treatment for severe disciplinary problems in children from violent homes. METHOD: Participants were 15 children (aged 3-10 years) and their mothers. All participants had experienced long-term family violence. Using a multiple-baseline design, the authors trained parents in a group format and conducted observations of child compliance in the home throughout the intervention. RESULTS: Observations indicated improvements in generalized child compliance that were maintained up to 6 months posttreatment. Pre-/post maternal reports indicated significant reductions in maternal perception of child noncompliance, externalizing and internalizing problems, and parenting stress. CONCLUSIONS: Researchers have noted a dearth of empirically supported interventions for children from violent homes. Errorless compliance training may help to fill this void, as it appears well suited to treatment of difficulties encountered by these youngsters and their parents.

Adult↗
PubMed1999

Fourteen-year follow-up of children with and without speech/language impairments: speech/language stability and outcomes.

This report concerns the speech and language outcomes of young adults (N = 242) who participated in a 14-year, prospective, longitudinal study of a community sample of children with (n = 114) and without (n = 128) speech and/or language impairments. Participants were initially identified at age 5 and subsequently followed at ages 12 and 19. Direct assessments were conducted in multiple domains (communicative, cognitive, academic, behavioral, and psychiatric) at all three time periods. Major findings included (a) high rates of continued communication difficulties in those with a history of impairment; (b) considerable stability in language performance over time; (c) better long-term outcomes for those with initial speech impairments than for those with language impairments; and (d) more favorable prognoses for those with specific language impairments than for those with impairments secondary to sensory, structural, neurological, or cognitive deficits. These general conclusions held when either a liberal or a more stringent criterion for language impairment was employed. Some of these findings are consistent with those from earlier follow-up studies, which used less optimal methods. Thus, the present replication and extension of these findings with a sound methodology enables greater confidence in their use for prognostic, planning, and research purposes.

Adolescent↗
PubMed1999

Adolescent substance use disorders: findings from a 14-year follow-up of speech/language-impaired and control children.

Intervening on the development of adolescent addiction requires an understanding of the role of precursors. In a community sample of youth with and without early childhood speech/language (S/L) impairments, 12.7% of participants had a substance use disorder (SUD). Among these participants, 42.0% met criteria for more than 1 SUD. Interestingly, rates of SUDs did not differ by S/L status. However, S/L-impaired participants did show greater psychiatric comorbidity and poorer functioning. A total of 80% of S/L participants with SUDs had a concurrent diagnosis of antisocial personality disorder, compared with 43.8% of SUDs controls. In a logistic regression analysis, we found age 5 mother-rated problem behavior scores and an interaction between S/L status and teacher-rated conduct problem scores were predictive of SUDs. High conduct scores were predictive of SUDs development among control participants but not among S/L-impaired participants. First substance use and initial SUDs symptoms suggest that a window of opportunity exists to reach these troubled young people before they spiral into addiction.

Adolescent↗
PubMed1997

Serum LH concentrations in hypogonadal men during transdermal testosterone replacement through scrotal skin: further evidence that ageing enhances testosterone negative feedback. The Testoderm Study Group.

OBJECTIVE: The present study was designed to explore further the mechanism for the decline in androgen production as men age by studying the influence of ageing on testosterone negative feedback control of gonadotrophin secretion. DESIGN: Circulating testosterone, dihydrotestosterone, oestradiol, SHBG and LH concentrations were measured during long-term treatment of men with primary hypogonadism using transdermal testosterone via scrotal skin. PATIENTS: Results were compared in 12 hypogonadal men below age 40 years (34 +/- 1.1 years; mean +/- SEM), 13 middle-aged men, aged 51 +/- 2.2 years, and 10 men age 64 years or older (68 +/- 1.4 years). RESULTS: During the course of therapy, circulating LH levels were suppressed 48% (F = -2.42, P = 0.018) from 19.6 +/- 6.0 IU/I at baseline to 10 +/- 7.7 IU/I during month 15 in elderly men. By contrast, LH levels were unchanged (F = 0.31; P = 0.97) in young men (20.3 +/- 7.4 IU/I at baseline and 17.7 +/- 14.9 IU/I during treatment month 15). Intermediate results were observed in middle-aged men in whom LH levels declined slightly (F = 1.34; P = 0.24). Transdermal testosterone treatment produced similar circulating testosterone levels (F = 1.49; P = 0.24) and oestradiol levels (F = 0.60; P = 0.42) in elderly and young men. Mean plasma DHT levels were approximately 20% higher (F = 9.91; P = 0.01) during treatment in elderly men overall mean values of 8.03 +/- 0.37 nmol/l) than in young men (6.68 +/- 0.08 nmol/l). When total DHT was adjusted for higher plasma SHBG levels in elderly men, the free DHT index during treatment was similar (F = 0.23; P = 0.64) in both groups. CONCLUSIONS: These data provide further evidence that the set point for androgen negative feedback control of gonadotrophin accretion in men is altered by ageing. Taken together with previous findings, these results provide a potential explanation for the unchanged or slightly increased plasma LH levels and reduced testosterone production characteristic of elderly men. Accordingly, ageing-associated Leydig cell insufficiency leads to a decline in testosterone production, but circulating LH levels do not rise appropriately because the set-point for negative feedback is decreased.

Administration, Cutaneous↗