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Biomedical subjects

M Place

Publications and source records attributed to M Place.

At least 19 recordsLinked to original sources
PubMed2004

Social communication deficits in conduct disorder: a clinical and community survey.

BACKGROUND: Increasing numbers of children are referred to Child and Adolescent Mental Health Services because of disruptive behaviour. Recent reviews on the origins of conduct problems indicate that the most severe and persistent forms are found predominantly among males with a range of neurodevelopmental vulnerabilities, which are likely to have biological substrates. In this study, we tested the hypothesis that many children who are identified with conduct disorder actually have a primary deficit in pragmatic language skills, of a quality and degree that is similar to children on the autistic spectrum. We hypothesised that pragmatic difficulties may underlie the antisocial behaviour in a proportion of children who are labelled as conduct disordered. METHODS: Using the Children's Communication Checklist (Bishop, 1998), we surveyed 142 children who had been referred for clinical investigation, with a predominant diagnosis of either an autistic spectrum condition (n = 87) or conduct disorder (n = 55), and 60 typically developing comparison children. Among children with conduct disorders, males predominated 9:1. RESULTS: On the basis of parent and teacher ratings, two-thirds of those with conduct disorders had pragmatic language impairments and other behavioural features similar in nature and degree to those of children with autism, independent of IQ. In a further study, we surveyed 54 children who had been excluded from elementary schools in a socio-economically disadvantaged inner-London borough and found over two-thirds to have comparable deficits. CONCLUSIONS: These findings have both theoretical and practical implications. First, they indicate the presence of communicative problems in a sub-group of children in whom conduct rather than language had been the major concern. Second, they indicate that severe deficits in pragmatic abilities and autistic-like behaviours can coexist with psychiatric conditions other than autism, especially in boys. Third, they imply that the management of many disruptive children could profitably be addressed to ameliorating their social and communicative skill deficits.

Autistic Disorder↗
PubMed1999

Dynamics of bed use in accommodating emergency admissions: stochastic simulation model.

OBJECTIVE: To examine the daily bed requirements arising from the flow of emergency admissions to an acute hospital, to identify the implications of fluctuating and unpredictable demands for emergency admission for the management of hospital bed capacity, and to quantify the daily risk of insufficient capacity for patients requiring immediate admission. DESIGN: Modelling of the dynamics of the hospital system, using a discrete-event stochastic simulation model, which reflects the relation between demand and available bed capacity. SETTING: Hypothetical acute hospital in England. SUBJECTS: Simulated emergency admissions of all types except mental disorder. MAIN OUTCOME MEASURES: The risk of having no bed available for any patient requiring immediate admission; the daily risk that there is no bed available for at least one patient requiring immediate admission; the mean bed occupancy rate. RESULTS: Risks are discernible when average bed occupancy rates exceed about 85%, and an acute hospital can expect regular bed shortages and periodic bed crises if average bed occupancy rises to 90% or more. CONCLUSIONS: There are limits to the occupancy rates that can be achieved safely without considerable risk to patients and to the efficient delivery of emergency care. Spare bed capacity is therefore essential for the effective management of emergency admissions, and its cost should be borne by purchasers as an essential element of an acute hospital service.

Bed Occupancy↗
PubMed1999

Validating the Ontario Child Health Scale in a UK population.

The Ontario Child Health Scale (OCHS) was one of the first scales to seek to assess a broad range of formally defined psychiatric disorders using a checklist format. The performance of the teacher version of this instrument is reported in a UK population of children attending a special educational provision for emotionally and behaviourally disordered (EBD) pupils. Against DSM-IV criteria the instrument proved to have retained its convergent and discriminant validity, although it was somewhat less effective in detecting internalizing disorders and discriminating oppositional defiance from other behavioural disorders. Overall the results confirm the usefulness of this instrument as a screening tool in a UK population.

Adolescent↗
PubMed1998

Primary cares. Messages from the frontline.

The biggest hurdle in the establishment of primary care groups is practices' reluctance to co-operate. GPs will want compensation for the time spent on administration. There is little awareness of the fact that PCG budgets may run out. The development of PCGs is expected to lead to an increase in salaried GPs. Current IT systems are seen as inadequate for PCGs.

Budgets↗
PubMed1997

The ability of teacher reports to identify child sexual abuse victims.

This study concerns the validation of an instrument, the SAB2, designed to measure child behaviour and to help identify emotional problems which arise because the child has been a victim of child sexual abuse. Clinically disturbed children, mainstream school children and sexually abused youngsters were assessed. Reliability and validity tests were carried out and a factor analysis was performed which produced seven factors. Finally, the mean factor scores of 35 sexually abused girls were compared with a control sample of 112 girls. The sexual abuse group was found to have significantly higher mean scores than controls on all factors and on the total instrument score. However, closer examination of the scores revealed that 15 of the female sexually abused group did not display any problematic behaviours, whereas the other 20 presented with high scores on all factors and a significantly higher score than any other group on the sexual behaviour factor. The instrument was capable of distinguishing behavioural disturbance arising from sexual abuse from that arising from other sources. However, the instrument failed to detect the 15 "silent' abused cases. It is unclear whether this sub-group has protective factors operating which minimise (or help to mask) the impact of sexual abuse, or whether the effects of the abuse will manifest later in life.

Adolescent↗
PubMed1995

Purification and characterization of recombinant varicella-zoster virus glycoprotein gpII, secreted by Chinese hamster ovary cells.

Chinese hamster ovary cells have been engineered to secrete an anchorless form of the varicella-zoster virus gpII protein. Purification of the recombinant product was achieved by a combination of hydrophobic and gel filtration chromatography giving rise to a protein more than 85% pure. Recombinant gpII was composed of several polypeptides which, on the basis of amino-terminal sequence analysis, corresponded to a 93-kDa precursor and to the N- and C-terminal subunits of the molecule (64 and 39/36 kDa, respectively). All polypeptides carried N-linked high-mannose and complex glycosylations, whereas O-glycosylations were carried by the precursor and the N-terminal subunits only. Surprisingly, purified recombinant gpII spontaneously formed large oligomeric structures of variable size. These complexes contained noncovalently linked lipids. Mice inoculated with the recombinant gpII absorbed onto the weak adjuvant, aluminium hydroxide, produced virus neutralizing antibodies. The recombinant gpII may thus constitute a good candidate for the development of a subunit vaccine against varicella-zoster virus.

Amino Acid Sequence↗
PubMed1993

Induction of neutralizing antibodies by varicella-zoster virus gpII glycoprotein expressed from recombinant vaccinia virus.

The gpII glycoprotein of varicella-zoster virus (VZV) was produced in CV1 cells via vaccinia virus recombinants. Two different DNA constructs were expressed: the first one encodes the complete gpII protein (gpII s+a+) and the second a truncated species lacking the membrane anchorage domain (gpII s+a-). To achieve expression both coding sequences had to be engineered at the 5' end by substituting the unusually short (24 bp) natural signal sequence by a more conventional one encoding 29 amino acids. Recombinant gpII proteins were detected in vaccinia virus-infected cells by ELISA and immunoprecipitation. Both forms of recombinant gpII proteins were produced as glycosylated single-chain molecules of respectively 110K and 90K. Upon reduction these were only partially converted into subunits. A rabbit infected with the vaccinia virus recombinant expressing the complete gpII produced antibodies which recognized VZV antigens and neutralized VZV infectivity in vitro, independent of complement.

Amino Acid Sequence↗
PubMed1990

Combining day patient treatment with family work in a child psychiatry clinic.

The 81 youngsters who began attending a day treatment programme within a 1-year period were assessed using an interval design. The children ranged in age from 18 months to 16 years and attended with similarly aged children for 1 day a week. The treatment programme combined family therapy with the day unit's milieu therapy and specific individual treatment programmes for the child. The results indicate that the combination of a 1 day a week attendance and family therapy had a significant clinical impact upon the problems. The pattern of improvement observed would suggest that the day-unit attendance made a unique contribution to the overall outcome.

Adolescent↗
PubMed1988

RNA binding to the untransformed glucocorticoid receptor. Sensitivity to substrate-specific ribonucleases and characterization of a ribonucleic acid associated with the purified receptor.

The cytosolic untransformed molybdate-stabilized glucocorticoid-receptor complex from rat liver was eluted as a heterogenous peak containing two components with Stokes radii (Rs) of 8.3 nm and 7.1 nm when analyzed by size-exclusion HPLC even in the absence of molybdate. In contrast, the highly purified glucocorticoid receptor yielded a sharp symmetrical peak of Rs = 7.1 nm. We demonstrate that the 7.1-nm component could not result from a proteolytic degradation of the 8.3-nm receptor form. The same receptor heterogeneity was observed in thymus cytosol which contains less proteases than liver. After labeling with [3H]dexamethasone 21-mesylate and SDS/PAGE the same 94-kDa receptor band was revealed in both the 8.3-nm and 7.1-nm forms. Immunoblotting experiments showed that both the 94-kDa hormone-binding subunit and the 90-kDa heat-shock protein were present in the two different receptor forms. The 8.3-nm receptor form was converted to the 7.1-nm receptor form after treatment by ribonuclease A in the presence of molybdate and this effect was dose-dependent, being completely prevented by placental ribonuclease inhibitor (RNasin). In contrast, in the presence of molybdate, the 7.1-nm receptor form was ribonuclease-insensitive. Treatment of cytosol with RNase A in the absence of molybdate, partially shifted the untransformed receptor towards the 5.2-nm transformed receptor form. This effect was abolished by placental ribonuclease inhibitor. RNase S protein, an enzymatically inactive proteolytic fragment of RNase A, or S1 nuclease, which is specific for single-stranded nucleic acids, were ineffective when used instead of RNase A. In contrast, cobra venom endonuclease, which preferentially attacks double-stranded regions of small RNAs, caused a complete conversion of the 7-8-nm untransformed receptor to the 5.2-nm transformed receptor form. These results were not observed in the presence of molybdate. Addition of RNasin prior to heating cytosol in the absence of molybdate did not prevent the receptor from dissociating to the 5.2-nm form, suggesting that an endogenous RNase is not involved in the transformation process. The 7.1-nm receptor form was shifted to a 9.2-nm complex when incubated with an excess of GR 49 antireceptor antibody, whereas the 8.3-nm receptor form did not bind to the antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Glucocorticoid receptors bound to the antagonist RU486 are not downregulated despite their capacity to interact in vitro with defined gene regions.

Modulation of gene expression by glucocorticoids involves interaction of these hormones with an intracellular receptor followed by 'transformation' of the hormone-receptor complex into a nuclear binding form. The molecular basis for the antiglucocorticoid action of high-affinity steroid analogues such as RU486 remains controversial. The effects of dexamethasone and RU486 on in vitro and in vivo properties of the receptor were compared using human lymphoblastoid IM-9 cells. In these cells, RU486 fully antagonized the glucocorticoid-specific induction of 5'-nucleotidase activity by dexamethasone. In vitro, however, RU486-bound receptor could be transformed and shown to interact specifically with cloned DNA fragments containing glucocorticoid response elements. These fragments included one from the mouse mammary tumour virus and two from the human growth hormone gene. In vivo, RU486-bound receptor did not behave like dexamethasone-bound receptor. While receptor downregulation, a property of the transformed receptor, was achieved by dexamethasone, this did not occur with RU486. Likewise, RU486 did not affect receptor half-life under conditions when this was shortened by dexamethasone. These seemingly contradictory results can be reconciled by proposing that receptor transformation by agonists involves dissociation of the receptor oligomer to reveal a DNA-binding site that pre-exists on this protein. Although cell-free receptor dissociation and therefore DNA binding can occur even when the receptor is bound to RU486, this steroid maintains receptors in the untransformed state in the intact cell and therefore behaves a glucocorticoid antagonist in vivo.

5'-Nucleotidase↗
PubMed1987

The relative value of screening instruments in adolescence.

The phase of development that equips a child to become an adult is a period of transition. To date no instrument has become established as the routine screening measure for this age group in the same way as the Rutter B2 Scale has in children. During a major population study of adolescent functioning, the pupils drawn from four comprehensive schools were used to compare the validity of several screening measures in this age group. The results show that screen instruments tend to be behaviour specific and that antisocial and neurotic behaviour are relatively sex specific. The Rutter Malaise Inventory had the highest correlation with the psychiatrist's diagnosis of neurotic disorder, although the General Health Questionnaire also proved to be reasonably efficient. The antisocial subscale of the Rutter B2 Scale showed the best correlation with the psychiatrist's diagnosis of conduct disorder.

Adolescent↗
PubMed1987

The Newcastle Adolescent Behaviour Screening Questionnaire.

As part of a larger study, a brief rating-scale was developed which focuses on the mid-adolescent phase of development. Completed by teachers, the questionnaire has an inter-rater reliability of 0.78, with a test-retest correlation of 0.82. When the performances of various screening instruments were compared it became clear that no single questionnaire was obviously more efficient than the others at detecting potential disturbance in an urban adolescent population. Indeed, different questionnaires seemed to highlight particular facets of functioning. The Newcastle Adolescent Questionnaire proved to be a reliable and valid screening measure.

Adolescent↗
PubMed1986

Youngsters who persistently do not attend school.

5% of the children attending psychiatric clinics in the UK have difficulties with school attendance and these stem from difficulties which are predominantly social (truancy) or predominantly psychological or dynamic (school refusal). Adolescents who display school refusal are three times more likely to develop neurotic difficulties in adult life, especially if marked family difficulties are persistent. Up to 20% of the senior school pupils may truant in a 2-week period and teachers report these youngsters to be more aggressive and to show more neurotic symptoms then the regular school attenders. Their peers choose them significantly less often as friends, and the marked differences in the rate of absence between schools seems related to school philosophy and the degree of school involvement in the community. Truancy can be influenced by greater vigilance in the school and by legal intervention. Although absence from school in itself does not seem to adversely influence the youngsters' adult functioning, if it is associated with conduct problems and educational retardation, long-term difficulties are common.

Absenteeism↗
PubMed1985

The difficult adolescents who are referred to a psychiatric unit--I. Classification.

The first 206 cases referred to an adolescent psychiatry unit were coded on a clinical inventory. This inventory proved to have acceptable inter-rater and test retest reliability, as well as quite a high degree of validity. Cluster analysis using Yule's similarity coefficient produced a series of near neighbours which, when combined with relevant history details produced four diagnostic groupings which seem to have clinical relevance to referrals to an adolescent psychiatric clinic. The importance of correct diagnosis in this age group is emphasized because of the part it plays in the search for more effective treatments of adolescent disorders.

Adolescent↗
PubMed1985

The difficult adolescents who are referred to a psychiatric unit--II. Clinical features and response to treatment.

The development of a new adolescent psychiatric unit for an urban area afforded the opportunity to study the range of cases that were referred. Using a special inventory that was developed and validated for the project distinct groups of youngsters were identified and their family characteristics studied. Of the conduct disordered group, a large proportion proved to be rather solitary and impulsive with a tendency towards outbursts of aggression. These adolescents and their families found least benefit from the family orientated approach of the unit. Of the remaining youngsters about 70 per cent showed symptomatic improvement, a rate which compares well with the findings from other outcome studies.

Adolescent↗