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Biomedical subjects

Andrew Lewis

Publications and source records attributed to Andrew Lewis.

8 recordsLinked to original sources

Development of an instrumented pole test for use as a gait laboratory quality check.

Gait analysis is becoming an increasingly common procedure in the diagnosis of movement disorders. Core equipment includes 3D tracking cameras and force platforms. Important clinical decisions are made with the assistance of gait data, therefore it is essential to have confidence in its quality. Calibration has a major role to play here and this paper describes the development of a daily spot check pole test for use in a gait laboratory. The work develops previous such tests, by the addition of a force transducer, removing the need to assume an idealised force system and allowing amplifier gain ranges to be checked. Repeatability results are presented, along with the response to 14 simulated error modes. The test provides useful data on system performance and is able to identify and diagnose failures. Failure thresholds can be tightened as accuracy improves, particularly in the area of centre of pressure measurement. Spot checks, such as this, along with full calibration tests, will become essential as new standards are introduced into clinical practice.

Biomechanical Phenomena↗

Structure-activity-relationship studies of conformationally restricted analogs of combretastatin A-4 derived from SU5416.

A series of combretastatin A-4 analogs derived from the ATP competitive, VEGF receptor tyrosine kinase inhibitor, SU5416 were synthesized. The cytotoxic effects of the analogs were evaluated against PC-3 and MDA-MB-231 cancer cell lines, as well as their abilities to inhibit tubulin polymerization. Results are compared to those of compound 1, our lead compound previously reported.

Antineoplastic Agents, Phytogenic↗

Mother-infant psychotherapy and perinatal psychiatry: current clinical practice and future directions.

OBJECTIVE: To explore trends in the practice of mother-infant psychotherapy among perinatal psychiatry clinicians based in Melbourne. METHODS: A cross-sectional survey with a purpose designed self-report questionnaire was used to assess the attitudes and practices of 47 perinatal and infant psychiatry clinicians in their use and understanding of mother-infant psychotherapy. RESULTS: Seventy per cent of clinicians in this field of psychotherapy who responded to the questionnaire subscribe to a psychodynamic model, although cognitive behavioural models are also used. The interventions were mostly used in conjunction with other interventions, would be more accurately described as 'parent-infant psychotherapy', and non-psychiatrists in the area tended to be more likely to be formally trained in psychotherapy, but only 4% were formally trained in specific mother-infant psychotherapy. There was a unanimous request for further clinical training in this area. CONCLUSIONS: The emerging field of perinatal psychiatry needs to develop coherent therapeutic models and conduct outcome trials on specific interventions. Specific trainings in these models, in assessment and in diagnostic frameworks are required to enhance clinical efficacy, for research and service development purposes.

Adult↗

A thalidomide analogue with in vitro antiproliferative, antimitotic, and microtubule-stabilizing activities.

We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G2-M arrest, which occurred mainly at the mitotic phase. In addition, immunofluorescence microscopy and in vitro tubulin polymerization studies showed that 5HPP-33 has antimicrotubule activity with a paclitaxel-like mode of action. It is effective against four different paclitaxel-resistant cell lines. Thus, 5HPP-33 represents a potential antitumor agent.

Animals↗

Conformationally restricted analogs of Combretastatin A-4 derived from SU5416.

A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti-microtubule agent Combretastatin A-4, inhibited tubulin polymerization, and showed potent growth inhibitory activities on both prostate and breast cancer lines with IC(50) values in low to subnanomolar range.

Animals↗

Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites.

Disposition kinetics of [(3)H]palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [(3)H]palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [(3)H]palmitate and metabolites were measured in four experimental groups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [(3)H]palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [(3)H]palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [(3)H]palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins.

Albumins↗

Safe working hours--doctors in training a best practice issue.

In 1995, the Australian Medical Association launched its Safe Working Hours campaign. By 1998, this had been developed into a National Code of Conduct that continues to resonate in the Australian public health system. However, and particularly in respect of Doctors in Training (DITs) who continue to work long hours, there are levels of resistance to proposals that seek to re-organise work or change prevailing professional and cultural expectations. Long working hours have substantial impacts on a DIT's capacity to consistently deliver high quality patient care, dilute the effectiveness of their training regime and have negative consequences on their health, social life and family responsibilities. While public hospitals often maintain the view that minimal budget flexibility restricts their capacity to affect change in a positive way, in fact devisable productivity and efficiency gains can be achieved by reducing working hours. Further, the medical profession needs to consider whether long hours provide an optimal environment for quality learning and performance.

Australia↗