Biomedical subjects
Publications and source records attributed to Michael Dudley.
A general-purpose method that includes nearly all possible two-beam diffraction mechanisms is presented for calculating diffracted and specularly reflected X-ray intensities from single crystals. Based on this method, it is demonstrated that a small universal computational routine can be developed to accurately treat two-beam diffraction for any scattering geometry.
SAR studies in a series of related 3-(heteroarylthio)cephems determined that a relatively high chemical reactivity of the beta-lactam ring, modulated by electronic effects of substituents at C-3 and C-7, is necessary to achieve high in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA). Such high reactivity results in lowered hydrolytic stability and concomitantly increases susceptibility to beta-lactam ring opening mediated by serum enzymes. Therefore, optimization of anti-MRSA activity versus stability toward serum-mediated degradation required a fine balance of substituent effects. Serum stability studies (measured as percentage of parent drug degraded after 60 min incubation) revealed up to 80-fold difference in degradation rate in a series of closely related (3-heteroarylthio)cephems. Of the compounds evaluated, RWJ-333441 (MC-04,546) possessed the best balance of serum stability (6% degradation after 60 min incubation) and in vitro activity versus MRSA (S. aureus COL MIC=1 microgram/mL). Accordingly, RWJ-333441 displayed excellent in vivo efficacy versus methicillin-susceptible Staphylococcus aureus (MSSA, ED(50)=0.39 mg/kg in mouse sepsis model with S. aureus Smith) and good pharmacokinetic properties in the rat (Cl(total)=0.39 L/h/kg).
Explore the source record for details and available documents.
OBJECTIVE: In Nazi-occupied Europe, substantial numbers of psychiatrists murdered their patients while many other psychiatrists were complicit with their actions. This paper addresses their motivations and actions, and with particular reference to Australia, explores issues of contemporary relevance. METHODS: The events are reviewed in their historical context using mainly secondary sources. RESULTS: The assumption that the term "Nazi" denotes a closed and unrepeatable chapter is questioned. As with the Holocaust that followed, medical killing of psychiatric patients was an open secret with gradations of collective knowing. Perpetrators were impelled by pressure from peers and superiors, unquestioning obedience, racist ideology and careerism. Perpetrators and bystanders' denial was facilitated by use of deceptive language, bureaucratic and technical proficiency, and notions such as "a greater cause" or "sacred mission". Dissociation and numbing were common. Psychiatrists were the main medical specialty involved because Nazi race and eugenic ideology (accepted by many psychiatrists) targeted mentally ill people for sterilization and euthanasia, and because psychiatrists were state-controlled and tended to objectify patients. Few psychiatrists resisted. IMPLICATIONS: Nazi psychiatry raises questions about medical ethics, stigma and mental illness, scientific "fashions", psychiatry's relations with government, and psychiatrists' perceived core business. Psychiatric resistance to future similar threats should be based on commemoration, broad-based education and reflection on cultural values, strong partnerships between psychiatrists and patients, and willingness to question publicly policies and attitudes that disadvantage and stigmatize groups. The principle fundamental to all these practices is an orientation to people as subjects rather than objects.
In 1998-1999, two Area Health Services in NSW conducted a project to implement evidence-based service enhancements for the clinical management of young people who present with Deliberate Self Harm (DSH) behaviour. The present study examined what structures and procedures were required to implement and sustain evidence-based practice in different health care settings for patients with DSH behaviour. Service provision was assessed at three points during the initial project to assess the degree of change that occurred, and 9 months after the completion of the project to allow an assessment of sustainability of the service provision. We examined staff perceptions of the importance of education, management directives, policy and procedure changes, and cultural/attitudinal changes, in implementing clinical best practice. Results indicated that support from both service management and clinical staff is necessary for successful implementation of service enhancements. High levels of staff education and policy development were also associated with high levels of service performance. The best sustained enhancements were those that were developed by the services themselves.