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Biomedical subjects

L R Drew

Publications and source records attributed to L R Drew.

At least 19 recordsLinked to original sources
PubMed2000

The role of trans-acting factors and DNA-bending in the silencing of human beta-globin gene expression.

The molecular mechanisms which govern the develop-mental specificity of human beta-globin gene transcription have been studied in K562 cells, a human eyrthroleukemia line that expresses minimal beta-globin. Protein-binding analysis reveals that the 5' region contains three elements bound by trans-acting factors, beta-protein 1 (BP1) and beta-protein 2 (BP2). In vitro mutagenesis of each individual element in a beta-globin vector containing chloramphenicol acetyl-transferase (pCAT) followed by transient transfection into K562 cells increased levels of CAT activity 5. 5-fold higher than wild-type (wt) betaCAT, consistent with their silencing role. Mutagenesis of all three elements, however, resulted in activity significantly lower than wt betaCAT. BP1 and BP2 motifs have overlapping binding sites for high mobility group proteins (HMG1+2), DNA-bending factors, shown here to extrinsically bend the beta-globin promoter. Theoretically, mutations in all beta-protein binding sites could affect the binding of HMG1+2 sufficiently to impede DNA-protein and/or protein-protein interactions needed to facilitate constitutive gene expression. Placing two turns of DNA between BP1 and BP2 motifs also increased expression 3-fold, indicative of spatial constraints required for optimal silencing. However, insertion of the HMG1+2 DNA-bending motif (also equivalent to two turns) facilitates beta-silencing by re-establishment of BP1-BP2 proximity. Thus a combination of general DNA-bending and specific transcriptional factors appear to be involved in beta-globin silencing in the embryonic/fetal erythroid stage.

Adult↗
PubMed1999

Clozapine in community practice: a 3-year follow-up study in the Australian Capital Territory.

OBJECTIVE: This paper aims to present the first data on the long-term use of clozapine in an entire cohort of patients encountered in a community, the Australian Capital Territory. It examines the clinical and financial outcomes 3 years after the prescription of clozapine to a cohort of 37 patients. METHOD: Experience during the 2 years before clozapine was prescribed was compared with experience in the following 3 years on the basis of a retrospective review of official records. Data included hospital and hostel bed use and an estimate of treatment costs. In addition, changes in living circumstances and employment status were assessed and treating psychiatrists reported the presence of side effects and their impressions of clinical change since clozapine was prescribed. RESULTS: Compared with the preclozapine period, there were significant reductions postclozapine in hospital admissions (year 3) and hospital bed-days (year 2) by the total cohort and in hospital bed-days and hospital expenditure for those patients (n = 25) who remained on clozapine (years 2 and 3). There was no significant increase or decrease postclozapine in the estimated combined cost of treatment attributable to bed use (hospital or hostel), clozapine tablets, blood monitoring, and the employment of a Clozapine Coordinator. Clinically, all patients who stayed on clozapine were reported to be moderately or markedly improved. Five of nine patients who were not taking clozapine at study's end were unimproved or deteriorated. CONCLUSIONS: The findings of significant clinical improvement without evidence of increased cost lend support for the selective use of clozapine in community practice.

Adult↗
PubMed1996

Homeless, helpless and hospitalised: the travails of a Chinese refugee.

OBJECTIVE: To report the case of a Chinese refugee who presented with a brief reactive psychosis in the presence of significant stressors. CLINICAL PICTURE: A 30-year-old Chinese refugee, who fled alleged torture and persecution in China, presented with an acute, severe, paranoid psychosis. TREATMENT AND OUTCOME: This patient's psychosis was exacerbated by involuntary hospitalisation and treatment. The withdrawal of restrictive measures, cessation of medications and attention to his social needs led to an improvement in his condition. CONCLUSIONS: Involuntary treatment of a brief reactive psychosis in those who have been previously tortured may exacerbate the psychosis. Withdrawal of restrictions and advocacy for the patient may generate a therapeutic alliance with a positive outcome.

Adult↗
PubMed1994

Initial experiences with clozapine at Kenmore Psychiatric Hospital.

OBJECTIVE: To replicate overseas experience with clozapine, a new antipsychotic drug reputed to be effective in producing major improvement in a high proportion of patients with treatment-resistant schizophrenia. DESIGN AND SETTING: A prospective clinical trial at Kenmore Psychiatric Hospital, Goulburn, NSW. This paper is a preliminary communication covering 14 to 18 weeks after commencement of clozapine. PATIENTS: Twelve patients with treatment-refractory chronic schizophrenia, chosen on the basis of the severity of their disability. INTERVENTION: After existing medication was changed to be compatible with clozapine, it was reduced to the minimum level acceptable for staff and patient safety. Clozapine was then introduced gradually while other medication was withdrawn. OUTCOME MEASURES: Progress was monitored in terms of clinical presentation, side effects, use of supplementary medication and assessments by means of three standardised scaling systems. RESULTS: None of the patients deteriorated. Of six patients aged 35 years or less, three showed dramatic improvement and three showed clinically significant improvement. None of the six older patients showed major improvement, except that extrapyramidal symptoms were reduced in all cases. Drowsiness and hypersalivation were the only common side effects. CONCLUSIONS: These preliminary findings are consistent with results reported overseas.

Adult↗
PubMed1992

Treatment is an art to which science can contribute: the 2nd James Rankin Oration.

Working models-beliefs-are an essential element of behaviour. Clients' models and non-scientific treatment models, need to be respected. It is contended that, practically and theoretically, scientific models have little validity or relevance for understanding and managing addictive behaviour. The WHO model of drug use, with two added elements (the self and the functions of choice and decision making; and random variation of neurophysiological activities), is used as an example. The scientific method consists of dissecting a complex phenomenon into simpler parts, testing hypotheses about these parts, collecting and summating the data, and applying the conclusions to individual cases. It is presumed that if we know enough about a person then we can predict their future behaviour, including response to therapeutic interventions. Four major arguments are produced against that presumption. The scientific method depends upon the use of meaningful numbers (representing discrete, replicable categories) and its results are presented in statistical formats (with limited individual relevance). Measurement in the behavioural sphere is neither precise nor objective. This is critical with complex interactive systems (such as the WHO model) in which an apparently insignificant change in input can result in dramatic changes in output. Progress may have been made technically, e.g. to reduce relapse, but therapy remains an art. In future, scientific endeavours should be complemented by attention to other disciplines.

Journal Article↗
PubMed1992

Chance: a major factor in the causation of mental illness.

This paper questions the adequacy of traditional models of human behaviour, including models of functional mental illness. It is proposed that random (chance) variation is an invariable rule of nature which must apply to neurophysiological processes. Because of this, internal chance (random variation in neurophysiological processes) must be an important factor in determining the course and onset of mental illness. It is proposed that external chance--fortuitous changes in the complex pattern of interaction between physical and functional factors influencing behaviour--is also an important determinant of mental illness. It is proposed that many of the key characteristics of mental illness are explicable in terms of the properties of complex interactional systems.

Brain↗
PubMed1991

Morals, science and chance.

The importance of paradigms (models, hypotheses) is emphasized. It is proposed that the reductionist model has dominated the addiction field to the exclusion of existentialist models. The limits of reductionism (typified by the 1980 WHO model of alcohol and other drug use) are explored. Attention is drawn to the characteristics of complex dynamic systems, including their sensitivity to small changes in any factor and the unpredictability of their outcomes. The importance of the capacity of individuals to make choices and the role of chance (both external and internal) is highlighted. The implications for therapy are explored. It is affirmed that therapy is, and will always be, an art, but the technical competence of the therapist can influence effectiveness.

Journal Article↗
PubMed1986

Psychiatrists and drug use: implications of alternatives to the 'disease' concept.

The development of the disease concept of drug use and the application of the medical model of management of drug problems were an accompaniment of the growth of modern medicine. They have, however, been subject to considerable review and criticism. A positive response to such criticism is advocated. Consideration of the 'way of life leading to predicaments' model, based on the work of a number of authors, allows the identification of essential tasks in helping people out of predicaments and the clarification of roles that psychiatrists can and should play.

Humans↗