Medicine (Western Health) - Research Publications

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    Very early mobilization following acute stroke: Controversies, the unknowns, and a way forward
    Bernhardt, J (WOLTERS KLUWER MEDKNOW PUBLICATIONS, 2008-01)
    UNLABELLED: Evidence that organized stroke-unit care results in better outcome has led to positive changes in stroke service delivery around the world. It is well accepted that stroke rehabilitation should commence as early as possible for optimal recovery to be achieved. Exactly how early rehabilitation should start is controversial. Early mobilization (getting up out of bed within 24 h of stroke onset) is a wellestablished feature of acute stroke care in many Scandinavian hospitals. Elsewhere in the world, stroke protocols enforce bed rest for the first few days or foster long periods of bed rest after stroke. This paper aims to provide an overview of the topic of very early mobilization (VEM). It is divided into three sections: section 1 reviews the effects of bed rest and outlines arguments both for and against enforced bed rest after stroke; in section 2, VEM as a treatment for stroke and the limitations of existing literature in the field are described; and section 3 outlines the systematic approach that has been taken by our team of clinical researchers to the study the effect of VEM after stroke. CONCLUSION: VEM represents a simple, easy-to-deliver intervention, requiring little or no equipment. It is potentially deliverable to 85% of the acute stroke population and, if proven to be effective, may help reduce the significant personal and community burden of stroke. As current opinion about when mobilization should begin is divided, one way to move forward is through the conduct of a large high-quality clinical trial (such as A Very Early Rehabilitation Trial (AVERT)). Although some inroads have been made, further research in this field is clearly warranted.
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    Depression: An Important Comorbidity With Metabolic Syndrome in a General Population
    Dunbar, JA ; Reddy, P ; Davis-Lameloise, N ; Philpot, B ; Laatikainen, T ; Kilkkinen, A ; Bunker, SJ ; Best, JD ; Vartiainen, E ; Lo, SK ; Janus, ED (AMER DIABETES ASSOC, 2008-12)
    OBJECTIVE: There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a sample representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components. RESEARCH DESIGN AND METHODS: Three cross-sectional surveys including clinical health measures were completed in rural regions of Australia during 2004-2006. A stratified random sample (n = 1,690, response rate 48%) of men and women aged 25-84 years was selected from the electoral roll. Metabolic syndrome was defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale and psychological distress by the Kessler 10 measure. RESULTS: Metabolic syndrome was associated with depression but not psychological distress or anxiety. Participants with the metabolic syndrome had higher scores for depression (n = 409, mean score 3.41, 95% CI 3.12-3.70) than individuals without the metabolic syndrome (n = 936, mean 2.95, 95% CI 2.76-3.13). This association was also present in 338 participants with the metabolic syndrome and without diabetes (mean score 3.37, 95% CI 3.06-3.68). Large waist circumference and low HDL cholesterol showed significant and independent associations with depression. CONCLUSIONS: Our results show an association between metabolic syndrome and depression in a heterogeneous sample. The presence of depression in individuals with the metabolic syndrome has implications for clinical management.
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    Association between raised blood pressure and dysglycemia in Hong Kong Chinese
    Cheung, BMY ; Wat, NMS ; Tso, AWK ; Tam, S ; Thomas, GN ; Leung, GM ; Tse, HF ; Woo, J ; Janus, ED ; Lau, CP ; Lam, TH ; Lam, KSL (AMER DIABETES ASSOC, 2008-09)
    OBJECTIVE: To investigate the association between raised blood pressure and dysglycemia. RESEARCH DESIGN AND METHODS: We studied the association between raised blood pressure and dysglycemia in 1,862 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. We determined the factors predicting the development of diabetes and hypertension in 1,496 subjects who did not have either condition at baseline. RESULTS: Diabetes and hypertension were both related to age, obesity indexes, blood pressure, glucose, HDL cholesterol, and triglycerides. Of subjects with diabetes, 58% had raised blood pressure. Of subjects with hypertension, 56% had dysglycemia. BMI and blood glucose 2 h after a 75-g oral glucose load were independent predictors of new-onset diabetes. Age, systolic blood pressure, and 2-h glucose were independent predictors of new-onset hypertension. BMI, systolic blood pressure, and 2-h glucose were independent predictors of the development of diabetes and hypertension together. CONCLUSIONS: Diabetes and hypertension share common etiological factors. Patients with diabetes or hypertension should be screened and managed for the precursor of the other condition.
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    Retinol-binding protein 4 and insulin resistance in polycystic ovary syndrome
    Hutchison, SK ; Harrison, C ; Stepto, N ; Meyer, C ; Teede, HJ (AMER DIABETES ASSOC, 2008-07)
    OBJECTIVE: Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating insulin resistance in overweight women with PCOS. RESEARCH DESIGN AND METHODS: At baseline, 38 overweight women (BMI >27 kg/m(2)) with PCOS and 17 weight-matched control subjects were compared. Women with PCOS were then randomly assigned to 6 months of a higher-dose oral contraceptive pill (OCP) (35 microg ethinyl estradiol/2 mg cyproterone acetate) or metformin (1 g b.i.d.). Outcome measures were insulin resistance (total insulin area under the curve) on an oral glucose tolerance test, RBP4, and metabolic/inflammatory markers. RESULTS: Overweight women with PCOS were more insulin resistant than control subjects, yet RBP4 levels were not different in women with PCOS versus those in control subjects (35.4 +/- 4.3 vs. 28.9 +/- 3.1 microg/ml, P = 0.36). RBP4 correlated with cholesterol and triglycerides but not with insulin resistance. Metformin improved insulin resistance by 35%, whereas the OCP worsened insulin resistance by 33%. However, RBP4 increased nonsignificantly in both groups (43.7 +/- 6.3 vs. 42.6 +/- 5.5 microg/ml, P = 0.92). CONCLUSIONS: Overweight women with PCOS were more insulin resistant than control subjects, but this finding was not reflected by RBP4 levels. RBP4 correlated with lipid levels but not with insulin resistance markers. RBP4 levels did not change when insulin resistance was reduced by metformin or increased by the OCP. These data suggest that RBP4 is not a useful marker of insulin resistance in PCOS but may reflect other metabolic features of this condition.
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    Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures
    Reid, CA ; Adams, BEL ; Myers, D ; O'Brien, TJ ; Williams, DA (BMC, 2008-07-02)
    BACKGROUND: Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg2+-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3. RESULTS: Within 24 hrs of the insult regional specific changes in neuronal firing patterns were evident as: (i) a dramatic reduction in the ability of CA3 to generate firing; and (ii) a contrasting increase in the frequency and duration of synchronized neuronal firing events in CA1. Two distinct processes underlie the increased propensity of CA1 to generate synchronized burst firing; a lack of ability of the CA3 region to 'pace' CA1 resulting in an increased frequency of synchronized events; and a change in the 'intrinsic' properties limited to the CA1 region, which is responsible for increased event duration. Neuronal quantification using NeuN immunoflurescent staining and stereological confocal microscopy revealed no significant cell loss in hippocampal sub regions, suggesting that changes in the properties of neurons within this region were responsible for the KA-mediated excitability changes. CONCLUSION: These results provide novel insight into adaptation of hippocampal circuits following excitotoxic injury. KA-mediated disruption of the interplay between CA3 and CA1 clearly increases the propensity to synchronized firing in CA1.