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Biomedical subjects

V Cooper

Publications and source records attributed to V Cooper.

At least 19 recordsLinked to original sources

Support for family carers of children and young people with developmental disabilities and challenging behaviour.

BACKGROUND: This study gathered information about perceptions of family carers of children and young people with developmental disabilities and challenging behaviour of the help, support and treatment received from services and professionals. METHODS: A total of 66 family carers completed postal questionnaires on the nature of, and their satisfaction with, services, professional help and advice received in respect of their family member's challenging behaviour. RESULTS: Most carers were dissatisfied with support and services received. Almost half reported receiving no professional input or none that was helpful. Over two-thirds reported receiving respite care but, in a third of these, the child had been excluded because of challenging behaviour. CONCLUSIONS: Families of children with challenging behaviour often do not receive services and supports that they find helpful. Treatments provided are not always evidence based. The 'rationing' of services creates a danger of inequality of access. We need a more proactive approach to identifying and meeting the need for family support.

Adolescent↗

Patients' perception of information about HAART: impact on treatment decisions.

The aim of this study was to profile patients' satisfaction with information they have received about HAART in relation to treatment uptake. As part of a prospective investigation into uptake and adherence to HAART, 115 participants, comprising predominantly gay men, completed validated questionnaires investigating their satisfaction with information relating to practical aspects and potential problems of HAART, perceptions of information from different sources and beliefs about HAART, following a clinically recommended treatment offer. There was a wide range of total satisfaction scores indicating variation in patients' information requirements. Those who declined HAART were less satisfied with the information they had received than those who accepted the treatment recommendation (p < 0.05). Lower levels of satisfaction were associated with stronger concerns about the potential adverse effects of HAART (p < 0.05). Furthermore, concerns about HAART were related to uptake of HAART with those declining treatment being significantly more concerned about potential adverse effects than those who accepted the treatment offer (p < 0.001). The most helpful sources of information were specialist HIV staff: hospital consultants, pharmacists and nurses, as well as other people with HIV. This study improves our understanding of how information about HAART is perceived by people faced with treatment decisions. It emphasizes the importance of providing information tailored to meet the needs of individual patients and address their specific concerns, in order to support informed decision making.

Adult↗

Perceptions of HAART among gay men who declined a treatment offer: preliminary results from an interview-based study.

As part of a prospective study of treatment decision making among people with HIV infection, we explored perceptions of HAART in a cohort who declined a treatment offer. This was a qualitative study in which 26 gay men were interviewed in relation to their views about HAART soon after treatment was recommended by their HIV physician. Fifteen themes were associated with the decision to decline HAART. These were grouped under three broad categories: doubts about personal necessity for HAART, concerns about potential adverse effects of taking HAART and satisfaction with the amount of personal control over the decision. These findings provide new insights into the type of beliefs that might inform people's evaluation of their perceived need for HAART and their concerns about HAART. Initiatives to support informed decisions should take account of these perceptions.

Adult↗

Teaching consultation skills in higher specialist training: experience of a workshop for specialist registrars in rheumatology.

OBJECTIVES: To design, implement and evaluate an initial communication skills workshop for higher specialist trainees in rheumatology, and to determine their prior experience of and attitude towards such training. METHODS: The setting for this study was a rheumatology specialist registrar study day in the West Midlands region of the UK. The workshop was jointly facilitated by a hospital specialist and a general practitioner educationist, providing both the credibility of subject expertise and experience of teaching consultation skills to groups of doctors. Simple, structured observations of pre-recorded consultations and simulations, based on scenarios from within the specialist field, were used. RESULTS: There was strong agreement amongst the trainees that the workshop was enjoyable and useful, that prior training and experience in this area was inadequate, and that it is feasible and important to develop the communication skills of hospital specialists. CONCLUSIONS: Undergraduate teaching in communication skills has been inadequate in the past and it receives little or no attention in most specialist training. There is a compelling argument for the inclusion of communication skills teaching in higher medical training within rheumatology. More work is required to research the optimum methods of delivering teaching in this area in a postgraduate setting, and to assess the impact of communication skills teaching on clinical practice.

Communication↗

The Maudsley long-term follow-up of child and adolescent depression. 1. Psychiatric outcomes in adulthood.

BACKGROUND: Strong links exist between juvenile and adult depression but comorbid conduct disorder in childhood may mitigate this continuity. AIMS: To test the impact of comorbid conduct disorder on psychiatric adult outcomes. METHOD: A group of 149 subjects assessed at the Maudsley Hospital in the period 1970-1983 and meeting DSM-IV criteria for major depressive disorder with (n=53) or without (n=96) conduct disorder were interviewed 20 years later. Data were collected on the lifetime history of psychiatric disorders. RESULTS: Adult depressive recurrence was high for major depression (62.4%) and any depression (75.2%), and survival analyses showed no difference between the two groups. The group with conduct disorders had higher rates of drug misuse and dependence, alcoholism and antisocial personality disorders. CONCLUSIONS: Adolescent depression carries an elevated risk of adult depression irrespective of comorbidity. Comorbid conduct disorder in childhood is associated with raised rates of other psychiatric outcomes.

Adolescent↗

The Maudsley long-term follow-up of child and adolescent depression. 2. Suicidality, criminality and social dysfunction in adulthood.

BACKGROUND: Strong links exist between juvenile and adult depression, but comorbid conduct disorder may be associated with worse adult social difficulties. AIMS: To test the impact of comorbid conduct disorder on social adjustment and dysfunction, suicidality and criminality of adults who had had depression as youths. METHOD: Subjects (n=149) assessed at the Maudsley Hospital in 1970-1983 and meeting DSM-IV criteria for major depressive disorder with (CD-MDD; n=53) or without (MDD; n=96) conduct disorder were interviewed 20 years later. Data were collected on lifetime psychiatric disorders and adult social/personality functioning. Death certificates and criminal records were obtained. RESULTS: The suicide risk was 2.45%, and 44.3% of the sample had attempted suicide once in their lives. Compared with the MDD group, the CD-MDD group had higher rates of suicidal behaviours and criminal offences, and exhibited more pervasive social dysfunction. CONCLUSIONS: Adolescent depression is associated with raised risks of adult suicidality and with persistent interpersonal difficulties. Youths with CD-MDD show more severe and pervasive social dysfunction.

Adolescent↗

UTP-preferring P2 receptor mediates inhibition of sodium transport in porcine thyroid epithelial cells.

1. The effects of adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP) and analogues on forskolin-stimulated absorption of Na+ by porcine thyroid epithelial cells were analysed in cultures grown as confluent monolayers on permeable supports in Transwell Ussing chambers. 2. 85% of the forskolin (10 microM)-stimulated short-circuit current was inhibited by phenamil (1 microM), which is a selective antagonist for epithelial type Na+ channels. 3. Phenamil-sensitive current was inhibited in a dose dependent manner by nucleotides added to the apical compartment of Ussing chambers. In contrast, the phenamil-resistant current, previously shown to represent anion secretion, was unaffected by nucleotides. 4. The order of potency (with EC50 values given in microM) was UTP (0.08)>>ATP (6.3)=uridine 5'-diphosphate (UDP) (6. 6)>2methyl-thio-adenosine-5'-triphosphate (2MeSATP) (84.5)>adenosine 5'-diphosphate (ADP) (147.8)>alpha,beta-methylene ATP (>150)>>adenosine (>1000). 5. P2 receptors mediating inhibition of sodium absorption were present on the apical membrane of the cells since addition of UTP (1-1000 microM) to the basal compartment of the Ussing chambers had little effect while subsequent addition to the apical compartment produced a normal response. 6. Cibachron blue (Reactive blue 2) (1-100 microM), an antagonist at some P2 receptor subtypes, inhibited phenamil sensitive current in a dose dependent manner with half maximal inhibition occurring at 14.25 microM. 7. Suramin (100 microM), pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS) (100 microM) and pyridoxal 5'-phosphate (P5P) (100 microM) showed only slight competitive antagonism against the response to UTP. 8 These results indicate that a UTP-preferring P2 receptor located on the apical membrane of thyroid epithelial cells mediates inhibition of Na+ absorption.

Animals↗

Linguistic processing during repetitive transcranial magnetic stimulation.

To determine if linguistic processing could be selectively disrupted with repetitive transcranial magnetic stimulation (rTMS), rTMS was performed during a picture-word verification task. Seven right-handed subjects were trained in two conditions: picture-word verification, which required the subject to verify whether the picture of an object matched the subtitle name on the same page, and frame verification, which required subjects to verify whether there was a rectangular frame around the combined object picture and subtitle. Half of the trials were performed during rTMS. The effects of rTMS on performance were evaluated at the following four scalp positions: left anterior (the area where rTMS produced speech arrest), a mirror site on the right, and two positions in the left and right parietal region. Stimulation over the left deltoid muscle served as a control. Subjects had less difficulty in making picture-word matching decisions during unstimulated compared with stimulated trials at the left anterior and posterior positions. No significant difference in accuracy was detected in the frame verification condition, but response times in the frame verification condition were longer with stimulation at the left anterior position. Because rTMS of the dominant hemisphere affected linguistic processing independent of speech motor output, we confirm that rTMS may be used to investigate language and other cognitive functions.

Adult↗

PET imaging of maze processing.

Covered maze traversal models nonverbal planning, involving sequential execution of moves using learned spatial maps. To determine the neural substrate involved in maze processing, eleven adults underwent [H(2)15O]-PET while performing motor control, following the computer; visual control, choosing the wall with more dead-ends; uncovered maze, traversing fully visible mazes; covered maze, traversing mazes only locally visible. Maze processing lateralizes to the right hemisphere: uncovered maze versus controls revealed area 23 and 29 activation; covered maze versus controls activated areas 8, 10 and 19. The extrastriate region may store path information, evoked by prefrontal areas for spatial planning and navigation.

Adolescent↗

Protein tyrosine phosphorylation influences adhesive junction assembly and follicular organization of cultured thyroid epithelial cells.

The follicular histoarchitecture of the thyroid forms the anatomical basis for thyroid physiology and is commonly disturbed in diseases of the thyroid. We have used cultured porcine thyroid cells to study thyroid epithelial morphogenesis and its regulation. When cultured in the presence of TSH, freshly isolated thyroid cells reorganize to form follicles within three-dimensional cell aggregates. However, when established follicles are washed into TSH-free medium, thyroid cells spread and migrate to convert follicles into confluent epithelioid monolayers, activating morphogenetic mechanisms, such as cell locomotility, that may be relevant to thyroid inflammation and tumor invasiveness. The phenomenon of follicle to monolayer conversion, therefore, provides an opportunity to identify morphogenetic mechanisms that 1) must be tonically inhibited to maintain follicular organization and 2) may contribute to pathogenetic disturbances of follicular architecture when functioning aberrantly. In this study we found that follicle to monolayer conversion is associated with an increase in cellular phosphotyrosine. This was particularly evident at nascent focal adhesions (cell-substrate adhesive junctions) and later at cell-cell junctions. Focal adhesion assembly was accompanied by reorganization of the actin cytoskeleton, with the appearance of prominent stress fibers. Genistein, a potent inhibitor of protein tyrosine kinases, inhibited the accumulation of phosphotyrosine, focal adhesion assembly, and follicle to monolayer conversion. We conclude that tyrosine phosphorylation exerts an important influence on thyroid epithelial organization in culture, at least partly mediated through regulation of focal adhesion assembly.

Animals↗

Isolation, biochemical characterization and ultrastructural analysis of the limbic system-associated membrane protein (LAMP), a protein expressed by neurons comprising functional neural circuits.

The limbic system-associated membrane protein (LAMP) is a cell surface glycoprotein expressed by cortical and subcortical regions of the mammalian CNS that comprise or receive direct projections from limbic system structures. The early and restricted expression of LAMP has led to its postulated role in neural development. Purification and biochemical characterization of LAMP was performed in order to ascertain its relationship to other, well-defined cell surface proteins in the nervous system. Subcellular fractionation, immunoaffinity chromatography, and Western blots of rodent and bovine hippocampus revealed that LAMP is an integral membrane protein with a molecular mass of 64-68 kDa and a pI of 5.2-5.5. Deglycosylation of LAMP indicates that it contains N-linked high mannose or hybrid sugars and a minor amount of sialic acid. The LAMP protein exhibits an identical molecular mass in developing hippocampus and in several different brain regions in the adult. No cross-reactivity was obtained using the monoclonal antibody that recognizes the HNK-1 carbohydrate epitope, a complex sulfated moiety expressed on members of a large family of glycoproteins. Immunocytochemical analysis at the ultrastructural level reveals that LAMP immunoreactivity is exhibited by neurons in a stereotyped pattern throughout limbic system areas. Glial cells are not immunoreactive. In the adult, LAMP-immunoreactive membrane patches are present exclusively postsynaptically on neuronal somata and dendrites. Myelinated and unmyelinated axons are not stained in any brain region examined. Analysis of LAMP expression in the developing CNS during synaptogenesis demonstrates that LAMP is located on growing axons and both pre- and postsynaptically at forming terminal complexes. Double-labeling studies of the hippocampal neurons grown in vitro reveal that the LAMP epitope is extracellular and is expressed on neurofilament- and microtubule-associated protein 2-positive neurites. Cells expressing glial fibrillary acidic protein are not LAMP-immunoreactive. These results demonstrate that in the adult brain, LAMP is expressed almost exclusively by the postsynaptic (target) elements in limbic circuits, but that during development, all components of the surface of the growing neuron contain LAMP. The stereotyped anatomical pattern of expression of LAMP in the developing and mature brain and its biochemical characteristics suggest that LAMP is a unique, system-associated membrane glycoprotein that is distinct from previously identified, developmentally important cell surface proteins.

Animals↗

Kernel estimates of dose response.

A nonparametric method for analyzing quantal response data from an indirect bioassay experiment is proposed. Kernel estimates of the dose-response curve are used to develop approximate confidence intervals for (i) the optimal combination dose of a drug with therapeutic effects at low doses and toxic effects at high doses, and (ii) the lethal dose levels of a toxic chemical. This nonparametric procedure was implemented on real and simulated data. The confidence interval for problem (i) has high coverage probabilities when the dose-response curve is symmetric about the optima. However, the coverage probabilities are adversely affected by asymmetry about the optima and consequently are not reliable unless the sample sizes are large. The use of kernel estimators with higher-order kernels may alleviate this sensitivity to asymmetry. The confidence interval for problem (ii) has high coverage probabilities robust with respect to the shape or symmetry of the underlying dose-response curve.

Animals↗

Models of spinal cord injury: Part 1. Static load technique.

Testing of potential therapies for spinal cord injury has been significantly hampered by the unavailability of a standardized, reproducible animal model with predictable outcome at a given force of injury (dose-response). The rat was selected in the development of this model in preference to larger animals for economy and availability; this permits use of large numbers of animals to increase statistical validity. In the experiments reported in this article, a static load method (weight placed gently on cord) of inducing cord injury was evaluated. A total of 198 Sprague-Dawley rats were used. Under general anesthesia, a one-level laminectomy was carried out at T-12 with the dura mater intact. Weights varying from 80 to 150 g were lowered onto the dorsal surface of the intact dura mater for durations of 0 to 300 seconds. Recovery of motor function was assessed for up to 8 weeks using two behavioral tests, a modified Tarlov scale and an inclined plane test of hind limb motor function. A statistically significant relationship was found between force of injury and motor recovery as measured by the Tarlov scale, but this did not correlate with inclined plane performance; the duration that the weight rested on the cord did not influence outcome. Pathologically, there was variation in the extent of damage for a given injury load. A semiquantitative pathological assessment of cord injury showed a statistically significant correlation between pathological score and behavioral deficit as measured by the Tarlov scale, but this did not correlate with inclined plane performance. In view of these deficiencies, the static load technique does not seem to be an ideal model for spinal cord injury research.

Animals↗