Research Report 2004–2005

The National Health and Medical Research Council Clinical Trials Centre has the purpose of improving outcomes in health through clinical trials research. It was established by the National Health and Medical Research Council in 1988 as a research centre at the University of Sydney. The CTC provides the knowledge and infrastructure to ensure the quality, timely completion and reporting of clinical trials. It has vast expertise in the design, conduct and analysis of randomised controlled trials, particularly in cancer and cardiovascular disease. Over 100 staff have specialised skills, taking in clinical trials design, biostatistics, database design, randomisation and drug distribution, outcome assessment, quality assurance, and regulatory and ethical issues. In the past 16 years, the CTC has participated in more than 50 investigatorinitiated, collaborative-group clinical trials and coordinated some of the largest randomised trials initiated by Australian investigators (LIPID and FIELD studies, each with over 9000 patients). Over 40 000 patients have been randomised to these trials. All clinical trials undertaken through the CTC are conducted strictly according to guidelines for clinical trials research and conduct, and are audited by sponsors, the CTC itself and regulatory authorities. The CTC has a history of working collaboratively with cooperative groups, clinical trial networks and other organisations, and has played a central role in establishing some of these groups. These activities have been recognised in increased grant funding to enable further collaboration and to increase the number of investigator-initiated trials in Australia. In its research, the CTC has prospered: it has developed strategies for patient recruitment, trial and data management, study coordination, information systems and randomisation in an environment of academic excellence. In addition to trials management, the CTC is a leader in biostatistical methodology and analysis and in systematic review of health evidence. The integrated expertise of the CTC staff is turned to good use in frequent educational activities in Australia and elsewhere. This report covers the CTC’s achievements for the biennium, 2004–2005

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Contains fulltext : 21333.PDF (publisher's version ) (Open Access

Inactivation of Apoe and Apoc1 by two consecutive rounds of gene targeting : effects on mRNA expression levels of gene cluster members

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Variability in Cholesterol Content in Serum and Aortic Tissue in Apolipoprotein E-Deficient Mice Is Comparable in Inbred (129/Sv) and Outbred (Mixed 129/Sv and C57bl/6) Mice

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Variability in cholesterol content in serum and aortic tissue in apolipoprotein E-deficient mice is comparable in inbed (129/Sv) and outbred (mixed 129/Sv and C57BL/6) mice.

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Cell membrane integrity in myotonic dystrophy type 1: implications for therapy

Contains fulltext : 154719.pdf (publisher's version ) (Open Access)Myotonic Dystrophy type 1 (DM1) is a multisystemic disease caused by toxic RNA from a DMPK gene carrying an expanded (CTG*CAG)n repeat. Promising strategies for treatment of DM1 patients are currently being tested. These include antisense oligonucleotides and drugs for elimination of expanded RNA or prevention of aberrant binding to RNP proteins. A significant hurdle for preclinical development along these lines is efficient systemic delivery of compounds across endothelial and target cell membranes. It has been reported that DM1 patients show elevated levels of markers of muscle damage or loss of sarcolemmal integrity in their serum and that splicing of dystrophin, an essential protein for muscle membrane structure, is abnormal. Therefore, we studied cell membrane integrity in DM1 mouse models commonly used for preclinical testing. We found that membranes in skeletal muscle, heart and brain were impermeable to Evans Blue Dye. Creatine kinase levels in serum were similar to those in wild type mice and expression of dystrophin protein was unaffected. Also in patient muscle biopsies cell surface expression of dystrophin was normal and calcium-positive fibers, indicating elevated intracellular calcium levels, were only rarely seen. Combined, our findings indicate that cells in DM1 tissues do not display compromised membrane integrity. Hence, the cell membrane is a barrier that must be overcome in future work towards effective drug delivery in DM1 therapy

Iron absorption during epoetin alfa therapy for chemotherapy-associated anaemia.

Item does not contain fulltextAbsorption of a physiological dose of ferrous iron was studied in 18 patients with solid malignancy receiving epoetin therapy for mild chemotherapy-associated anemia. The historical control group consisted of 25 iron replete volunteers (iron absorption 20 +/- 11% in males and 26 +/- 13% in females) and 21 patients with uncomplicated iron deficiency (iron absorption 71 +/- 19%). Iron absorption was increased in the majority of the cancer patients (iron absorption 59 +/- 35%). There were no significant differences in iron absorption between cancer patients who were iron replete or iron deficient according to current clinical practice guidelines (iron deficiency: transferrin saturation < 20% and/or serum ferritin < 100 ng/mL). Red cell iron incorporation was not disturbed in the majority (89%) of patients

Breaking bounds : Alice Profé, radical and emancipationist

La vie et l'oeuvre d'Alice Profé (1887-1946). Son combat pour l'égalité des sexes en Allemagne. Son activisme en faveur de la gymnastique féminine, de la culture physique et de la pratique sportive des femmes (promotion de l'aviron 'stylistique'), de la participation des femmes aux Jeux olympiques