Rapid determination of the active leflunomide metabolite A77 1726 in human plasma by high-performance liquid chromatography

A simple method for the measurement of the active leflunomide metabolite A77 1726 in human plasma by HPLC is presented. The sample workup was simple, using acetonitrile for protein precipitation. Chromatographic separation of A77 1726 and the internal standard, alpha-phenylcinnamic acid, was achieved using a C-18 column with UV detection at 305 nm. The assay displayed reproducible linearity for A77 1726 with determination coefficients (r(2)) > 0.997 over the concentration range 0.5-60.0 mug/ml. The reproducibility (%CV) for intra- and inter-day assays of spiked controls was

Environmental contamination of arsenic and its toxicological impact on humans

Inorganic arsenic compounds are known carcinogens. The human epidemiologic evidence of arsenic-induced skin, lung, and bladder cancers is strong. However, the evidence of arsenic carcinogenicity in animals is very limited. Lack of a suitable animal model until recent years has inhibited studies of the mechanism of arsenic carcinogenesis. The toxicity and bioavailability of arsenic depend on its solubility and chemical forms. Therefore, it is critical to be able to measure arsenic speciation accurately and reliably. However, speciation of arsenic in more complex matrices remains a real challenge. There are tens of millions of people who are being exposed to excessive levels of arsenic in the drinking water alone. The source of contamination is mainly of natural origin and the mass poisoning is occurring worldwide, particularly in developing countries. Chronic arsenicosis resulting in cancer and non-cancer diseases will impact significantly on the public health systems in their respective countries. Effective watershed management and remediation technologies in addition to medical treatment are urgently needed in order to avoid what has been regarded as the largest calamity of chemical poisoning in the world.

The use of online health techniques to assist with the delivery of specialist paediatric diabetes services in Queensland

We have tested an alternative method of delivering health services to regional areas of Queensland. By integrating telepaediatrics into an existing outreach programme for children with diabetes and endocrine conditions, we were able to reduce travel for specialist hospital staff while maintaining (and sometimes increasing) the contact patients had with the specialist team. In the first 28 months, we facilitated 160 patient consultations and 10 education sessions via videoconference through the telepaediatric service. By the end of the study, site visits were taking place annually and routine videoconference clinics were scheduled quarterly for the review of new patients and follow-up. Telepaediatric services in endocrinology and diabetes were established at three levels: the coordination of routine specialist clinics via videoconference; ad hoc patient consultations for collaborative management during acute presentations and at times of urgent clinical need; and the delivery of education to staff and patients throughout the state. The net result was improved access to specialist services from rural and remote areas of Queensland.

Young refugees talk about well-being: A qualitative analysis of refugee youth mental health from three states

Young people from refugee backgrounds face enormous challenges in the settlement process within Australia. They must locate themselves within a new social, cultural, geographic and adult space, yet also try to find security within the spaces of their own families and ethnic communities. Traumas of the past can mix with painful experiences of the present. The stressors in the lives of these young people can be both complex and diverse. This paper explores the nature a/these stressors among young people from refugee backgrounds living in Australia. [t is based On in-depth interviews with 76 young people from refugee backgrounds now living in Brisbane, Adelaide and Perth. A qualitative analysis of the impact of these stressors as well as the coping strategies employed are discussed It is argued that trauma exists

How young people from culturally and linguistically diverse backgrounds experience mental health: Some insights for mental health nurses

This article reports on part of a study that looked at the mental health of culturally and linguistically diverse (CALD) young people. The research sought to learn from CALD young people, carers, and service providers experiences relevant to the mental health of this group of young people. The ultimate goal was to gain insights that would inform government policy, service providers, ethnic communities and most importantly the young people themselves. To this end, qualitative interviews were undertaken with 123 CALD young people, 41 carers and 14 mental health service providers in Queensland, Western Australia and South Australia. Only one aspect of the study will be dealt with here, namely the views of the young CALD participants, which included risk factors, coping strategies and recommendations about how they could be supported in their struggle to maintain mental health. One of the most important findings of the study relates to the resilience of these young people and an insight into the strategies that they used to cope. The efforts of these young people to assist us in our attempts to understand their situation deserve to be rewarded by improvements in the care that we provide. To this end this article sets out to inform mental health nurses of the results of the study so that they will be in a position to better understand the needs and strengths of their CALD clients and be in a better position to work effectively with them.

Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies

Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published methods for the determination of free drug concentrations by HPLC-MS. The development of atmospheric pressure ionisation sources, together with on-line microdialysis or on-line equilibrium dialysis and column switching techniques have reduced sample run times and increased assay efficiency. The availability of such methods will aid in drug development and the clinical use of certain drugs, including anti-convulsants, anti-arrhythmics, immunosuppressants, local anaesthetics, anti-fungals and protease inhibitors. The history of free drug measurement and an overview of the current HPLC-MS applications for these drugs are discussed. Immunosuppressant drugs are used as an example for the application of HPLC-MS in the measurement of drug pharmacodynamics. Potential biomarkers of immunosuppression that could be measured by HPLC-MS include purine nucleoside/nucleotides, drug-protein complexes and phosphorylated peptides. At the proteomic level, two-dimensional gel electrophoresis combined with matrix-assisted laser desorption/ionisation time-of-flight (TOF) MS is a powerful tool for identifying proteins involved in the response to inflammatory mediators. (C) 2003 Elsevier Science B.V. All rights reserved.

Preliminary experience of allied health assessments delivered face to face and by videoconference to a residential facility for elderly people

We investigated whether allied health assessments carried out via videoconferencing were comparable to assessments carried out face to face. Five allied health therapists (in dietetics, occupational therapy, physiotherapy, podiatry and speech pathology) conducted an assessment of 12 high-dependency residents both face to face and by videoconferencing. On a five-point Likert scale, the therapists' mean ratings for the efficiency and suitability of videoconferencing for assessment were significantly lower than for face to face. Their mean rating for the adequacy of their care plans was also significantly lower for videoconferencing than for face to face. However, in each case the dietician's assessments did not differ significantly between the two modalities. In 35 cases out of 60, two independent raters agreed that the therapists' care plans after the videoconferencing and face-to-face assessments were the same. However, the level of agreement between raters was only moderate (kappa=0.31). Despite the therapists' (natural) preference for face-to-face working, care plans formulated via videoconferencing were reasonably similar to those formulated in face-to-face assessment. Allied health assessments carried out by videoconferencing would therefore seem to be feasible.

The cost of allied health assessments delivered by videoconference to a residential facility for elderly people

We calculated the cost of providing allied health assessments to high-dependency residents of a rural facility for elderly people. The costs of conducting assessments via videoconferencing were compared with the costs of conducting assessments face to face. The observed costs in a three-month pilot trial were used to estimate the annual costs. Given an annual workload of 1000 occasions of service, each videoconference assessment would cost $84.93, compared with $90.25 for face-to-face assessments. Allied health assessments delivered by videoconferencing became cheaper at workloads of approximately 850 occasions of service annually. Additional increases in the workload further improved the financial viability of this approach to service delivery.

How does mental health status relate to accessibility and remoteness?

Objective: To determine whether mental illness is associated with accessibility and remoteness. Design: A cross-sectional, population-based, computer-assisted telephone interview survey, stratified by Accessibility and Remoteness Index of Australia (ARIA) categories. Setting: Secondary analysis of data collected from 2545 South Australian adults in October and November 2000. Outcome measures: Psychological distress and depression as determined by the Kessler 10 Psychological Distress Scale, the SF-12 measure of health status, and self-reported mental illness diagnosed by a doctor in the previous 12 months. Results: Overall, mental illness prevalence estimates were similar using the three measures of psychological distress (10.5%), clinical depression (12.9%) and self-reported mental health problem (12.7%). For each measure, there was no statistically significant variation in prevalence across ARIA categories, except for a lower than expected prevalence of depression (7.7%) in the accessible category. There was no trend suggesting higher levels of mental illness among residents of rural and remote regions. Conclusions: The prevalence rates of psychological distress, depression and self-reported mental illness are high. However, we found no evidence that the prevalence of these conditions varies substantially across ARIA categories in South Australia. This finding may challenge existing stereotypes about higher levels of mental illness outside metropolitan Australia.

Using a non-invasive stable isotope tracer to measure the absorption of water in humans

The development of solutions that prevent dehydration or promote adequate re-hydration play a vital role in preventing fatigue during exercise, however, the methods commonly used to assess the hydration ability of such solutions are invasive and often assess the components of absorption separately. This paper describes using a non-invasive deuterium tracer technique that assesses gastric emptying and intestinal absorption simultaneously to evaluate the uptake of water during rest and exercise. The kinetics of absorption are further examined by mathematical modelling of the data generated. For the rest group, 0.05 g/kg of body weight of deuterium, contained in gelatine capsules, was ingested with ordinary tap water and saliva samples were collected every 5 min for one hour while the subject remained seated. The deuterium was administered as above for the exercise group but sample collection was during one hour of exercise on a treadmill at 55% of the subject's maximum heart rate. The enrichment data for each subject were mathematically modelled and the parameters obtained were compared across groups using an independent samples t-test. Compared with the rest condition, the exercise group showed delayed absorption of water as indicated by significant differences for the modelling parameters t(2), t(1/2), maximum absorption rate and solution absorption amount at t(1). Labelling with a deuterium tracer is a good measure of the relative rate ingested fluids are absorbed by the body. Mathematical modelling of the data generates rates of maximum absorption and allows calculation of the percentage of the solution that is absorbed at any given time during the testing period. Copyright (C) 2004 John Wiley Sons, Ltd.

Determination of protein charge by capillary zone electrophoresis

The feasibility of employing classical electrophoresis theory to determine the net charge (valence) of proteins by capillary zone electrophoresis is illustrated in this paper. An outline of a procedure to facilitate the interpretation of mobility measurements is demonstrated by its application to a published mobility measurement for Staphylococcal nuclease at pH 8.9 that had been obtained by capillary zone electrophoresis. The significantly higher valence of +7.5 (cf. 5.6 from the same series of measurements) that has been reported on the basis of a charge ladder approach for charge determination signifies the likelihood that the latter generic approach may be prone to error arising from nonconformity of the experimental system with an inherent assumption that chemical modification or mutation of amino acid residues has no effect on the overall three-dimensional size and shape of the protein. (C) 2004 Elsevier Inc. All rights reserved.

Determination of binding constants by affinity chromatography

This review summarizes developments in the use of affinity chromatography to characterize biospecific interactions in terms of reaction stoichiometry and equilibrium constant. In that regard, the biospecificity incorporated into the design of the experiment ensures applicability of the method regardless of the sizes of the reacting solutes. By the adoption of different experimental strategies (column chromatography, simple partition equilibrium, solid-phase immunoassay and biosensor technology protocols) quantitatiative affinity chromatography can be used to characterize interactions governed by an extremely broad range of binding affinities. In addition, the link between ligand-binding studies and quantitative affinity chromatography is illustrated by means of partition equilibrium studies of glycolytic enzyme interactions with muscle myofibrils. an exercise which emphasizes that the same theoretical expressions apply to naturally occurring examples of affinity chromatography in the cellular environment. (C) 2004 Elsevier B.V. All rights reserved.