Non-alcoholic fatty liver disease : can ultrasound assist in early diagnosis of prediabetes and delay progression to type2 diabetes mellitus

Non Alcoholic Fatty Liver Disease (NAFLD) is a condition that is frequently seen but seldom investigated. Until recently, NAFLD was considered benign, self-limiting and unworthy of further investigation. This opinion is based on retrospective studies with relatively small numbers and scant follow-up of histology data. (1) The prevalence for adults, in the USA is, 30%, and NAFLD is recognized as a common and increasing form of liver disease in the paediatric population (1). Australian data, from New South Wales, suggests the prevalence of NAFLD in “healthy” 15 year olds as being 10%.(2) Non-alcoholic fatty liver disease is a condition where fat progressively invades the liver parenchyma. The degree of infiltration ranges from simple steatosis (fat only) to steatohepatitis (fat and inflammation) steatohepatitis plus fibrosis (fat, inflammation and fibrosis) to cirrhosis (replacement of liver texture by scarred, fibrotic and non functioning tissue).Non-alcoholic fatty liver is diagnosed by exclusion rather than inclusion. None of the currently available diagnostic techniques -liver biopsy, liver function tests (LFT) or Imaging; ultrasound, Computerised tomography (CT) or Magnetic Resonance Imaging (MRI) are specific for non-alcoholic fatty liver. An association exists between NAFLD, Non Alcoholic Steatosis Hepatitis (NASH) and irreversible liver damage, cirrhosis and hepatoma. However, a more pervasive aspect of NAFLD is the association with Metabolic Syndrome. This Syndrome is categorised by increased insulin resistance (IR) and NAFLD is thought to be the hepatic representation. Those with NAFLD have an increased risk of death (3) and it is an independent predictor of atherosclerosis and cardiovascular disease (1). Liver biopsy is considered the gold standard for diagnosis, (4), and grading and staging, of non-alcoholic fatty liver disease. Fatty-liver is diagnosed when there is macrovesicular steatosis with displacement of the nucleus to the edge of the cell and at least 5% of the hepatocytes are seen to contain fat (4).Steatosis represents fat accumulation in liver tissue without inflammation. However, it is only called non-alcoholic fatty liver disease when alcohol - >20gms-30gms per day (5), has been excluded from the diet. Both non-alcoholic and alcoholic fatty liver are identical on histology. (4).LFT’s are indicative, not diagnostic. They indicate that a condition may be present but they are unable to diagnosis what the condition is. When a patient presents with raised fasting blood glucose, low HDL (high density lipoprotein), and elevated fasting triacylglycerols they are likely to have NAFLD. (6) Of the imaging techniques MRI is the least variable and the most reproducible. With CT scanning liver fat content can be semi quantitatively estimated. With increasing hepatic steatosis, liver attenuation values decrease by 1.6 Hounsfield units for every milligram of triglyceride deposited per gram of liver tissue (7). Ultrasound permits early detection of fatty liver, often in the preclinical stages before symptoms are present and serum alterations occur. Earlier, accurate reporting of this condition will allow appropriate intervention resulting in better patient health outcomes. References 1. Chalasami N. Does fat alone cause significant liver disease: It remains unclear whether simple steatosis is truly benign. American Gastroenterological Association Perspectives, February/March 2008 www.gastro.org/wmspage.cfm?parm1=5097 Viewed 20th October, 2008 2. Booth, M. George, J.Denney-Wilson, E: The population prevalence of adverse concentrations with adiposity of liver tests among Australian adolescents. Journal of Paediatrics and Child Health.2008 November 3. Catalano, D, Trovato, GM, Martines, GF, Randazzo, M, Tonzuso, A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study .Liver Int.2008; February 1280-9 4. Choudhury, J, Sanysl, A. Clinical aspects of Fatty Liver Disease. Semin in Liver Dis. 2004:24 (4):349-62 5. Dionysus Study Group. Drinking factors as cofactors of risk for alcohol induced liver change. Gut. 1997; 41 845-50 6. Preiss, D, Sattar, N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci.2008; 115 141-50 7. American Gastroenterological Association. Technical review on nonalcoholic fatty liver disease. Gastroenterology.2002; 123: 1705-25

Paramedic knowledge of infectious disease aetiology and transmission in an Australian Emergency Medical System

Introduction: Paramedics and other emergency health workers are exposed to infectious disease particularly when undertaking exposure-prone procedures as a component of their everyday practice. This study examined paramedic knowledge of infectious disease aetiology and transmission in the pre-hospital care environment.--------- Methods: A mail survey of paramedics from an Australian ambulance service (n=2274) was conducted.--------- Results: With a response rate of 55.3% (1258/2274), the study demonstrated that paramedic knowledge of infectious disease aetiology and modes of transmission was poor. Of the 25 infectious diseases included in the survey, only three aetiological agents were correctly identified by at least 80% of respondents. The most accurate responses for aetiology of individual infectious diseases were for HIV/AIDS (91.4%), influenza (87.4%), and hepatitis B (85.7%). Poorest results were observed for pertussis, infectious mononucleosis, leprosy, dengue fever, Japanese B encephalitis and vancomycin resistant enterococcus (VRE), all with less than half the sample providing a correct response. Modes of transmission of significant infectious diseases were also assessed. Most accurate responses were found for HIV/AIDS (85.8%), salmonella (81.9%) and influenza (80.1%). Poorest results were observed for infectious mononucleosis, diphtheria, shigella, Japanese B encephalitis, vancomycin resistant enterococcus, meningococcal meningitis, rubella and infectious mononucleosis, with less than a third of the sample providing a correct response.--------- Conclusions: Results suggest that knowledge of aetiology and transmission of infectious disease is generally poor amongst paramedics. A comprehensive in-service education infection control programs for paramedics with emphasis on infectious disease aetiology and transmission is recommended.

Development of a particle number and particle mass vehicle emissions inventory for an urban fleet

Motor vehicles are major emitters of gaseous and particulate pollution in urban areas, and exposure to particulate pollution can have serious health effects, ranging from respiratory and cardiovascular disease to mortality. Motor vehicle tailpipe particle emissions span a broad size range from 0.003-10µm, and are measured as different subsets of particle mass concentrations or particle number count. However, no comprehensive inventories currently exist in the international published literature covering this wide size range. This paper presents the first published comprehensive inventory of motor vehicle tailpipe particle emissions covering the full size range of particles emitted. The inventory was developed for urban South-East Queensland by combining two techniques from distinctly different disciplines, from aerosol science and transport modelling. A comprehensive set of particle emission factors were combined with traffic modelling, and tailpipe particle emissions were quantified for particle number (ultrafine particles), PM1, PM2.5 and PM10 for light and heavy duty vehicles and buses. A second aim of the paper involved using the data derived in this inventory for scenario analyses, to model the particle emission implications of different proportions of passengers travelling in light duty vehicles and buses in the study region, and to derive an estimate of fleet particle emissions in 2026. It was found that heavy duty vehicles (HDVs) in the study region were major emitters of particulate matter pollution, and although they contributed only around 6% of total regional vehicle kilometres travelled, they contributed more than 50% of the region’s particle number (ultrafine particles) and PM1 emissions. With the freight task in the region predicted to double over the next 20 years, this suggests that HDVs need to be a major focus of mitigation efforts. HDVs dominated particle number (ultrafine particles) and PM1 emissions; and LDV PM2.5 and PM10 emissions. Buses contributed approximately 1-2% of regional particle emissions.

Nursing students’ knowledge and practice of infection control precautions : an educational intervention

Aim. This paper is a report of the effectiveness of a purpose-designed education program in improving undergraduate nursing students’ understanding and practice of infection control precautions. Background. The severe acute respiratory syndrome outbreak in 2003 highlighted that healthcare workers were under-prepared for such an epidemic. While many in-service education sessions were arranged by institutions in response to the outbreak, preservice nursing education has overlooked preparation for handling such infectious disease epidemics. Method. A quasi-experimental design was used and a 16-hour, purpose-designed infection control education programme was implemented for preservice nursing students in southern Taiwan. Self-administered questionnaires were distributed at three time points during the period September 2005 to April 2006 to examine the sustainability and effectiveness of the intervention. Results. A total of 175 preservice nursing students participated in the study. Following the education programme, students in the intervention group showed a statistically significant improvement across time in their knowledge of these precautions [F(2, 180) = 13Æ53, P < 0Æ001] and confidence in resolving infectionrelated issues [F(1Æ79, 168Æ95) = 3Æ24] when compared with those in the control group. Conclusion. To improve nursing students’ capacity in responding to infectious epidemics, an educational programme that integrates the theme of infection precautions, learning theory and teaching strategies is recommended for all nursing institutes.

Corneal confocal microscopy : a novel noninvasive means to diagnose neuropathy in patients with Fabry disease

ABSTRACT: Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal esthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS)and heat-induced pain (HIP) were only significantly increased in males onERT (P<0.01). However, corneal sensation assessed withNCCAwas significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QSTand CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.

Ghrelin gene-related peptides : multifunctional endocrine/autocrine modulators in health and disease

Ghrelin is a multi-functional peptide hormone which affects various processes including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation. Ghrelin is produced in the stomach and in other normal and pathological cell types. It may act as an endocrine or autocrine/paracrine factor. The ghrelin gene encodes a precursor protein, preproghrelin, from which ghrelin and other potentially active peptides are derived by alternative mRNA splicing and/or proteolytic processing. The metabolic role of the peptide obestatin, derived from the preproghrelin C-terminal region, is controversial. However, it has direct effects on cancer cell proliferation. The regulation of ghrelin expression and the mechanisms through which the peptide products arise are unclear. We have recently re-examined the organisation of the ghrelin gene and identified several novel exons and transcripts. One transcript, which lacks the ghrelin-coding region of preproghrelin, contains the coding sequence of obestatin. Furthermore, we have identified an overlapping gene on the antisense strand of ghrelin, GHRLOS, which generates transcripts that may function as non-coding regulatory RNAs or code for novel, short bioactive peptides. The identification of these novel ghrelin-gene related transcripts and peptides raises critical questions regarding their physiological function and their role in obesity, diabetes and cancer.

Deposition of combustion aerosols in the human respiratory tract : comparison of theoretical predictions with experimental data

Total deposition of petrol, diesel and environmental tobacco smoke (ETS) aerosols in the human respiratory tract for nasal breathing conditions was computed for 14 nonsmoking volunteers, considering the specific anatomical and respiratory parameters of each volunteer and the specific size distribution for each inhalation experiment. Theoretical predictions were 34.6% for petrol, 24.0% for diesel, and 18.5% for ETS particles. Compared to the experimental results, predicted deposition values were consistently smaller than the measured data (41.4% for petrol, 29.6% for diesel, and 36.2% for ETS particles). The apparent discrepancy between experimental data on total deposition and modeling results may be reconciled by considering the non-spherical shape of the test aerosols by diameter-dependent dynamic shape factors to account for differences between mobility-equivalent and volume-equivalent or thermodynamic diameters. While the application of dynamic shape factors is able to explain the observed differences for petrol and diesel particles, additional mechanisms may be required for ETS particle deposition, such as the size reduction upon inspiration by evaporation of volatile compounds and/or condensation-induced restructuring, and, possibly, electrical charge effects.

Tesofensine : a novel potent weight loss medicine

Background: The incidence of obesity is increasing; this is of major concern, as obesity is associated with cardiovascular disease, stroke, type 2 diabetes, respiratory tract disease, and cancer. Objectives/methods: This evaluation is of a Phase II clinical trial with tesofensine in obese subjects. Results: After 26 weeks, tesofensine caused a significant weight loss, and may have a higher maximal ability to reduce weight than the presently available anti-obesity agents. However, tesofensine also increased blood pressure and heart rate, and may increase psychiatric disorders. Conclusions: It is encouraging that tesofensine 0.5 mg may cause almost double the weight loss observed with sibutramine or rimonabant. As tesofensine and sibutramine have similar pharmacological profiles, it would be of interest to compare the weight loss with tesofensine in a head-to-head clinical trial with sibutramine, to properly assess their comparative potency. Also, as teso fensine 0.5 mg increases heart rate, as well as increasing the incidence of adverse effects such as nausea, drug mouth, flatulence, insomnia, and depressed mode, its tolerability needs to be further evaluated in large Phase III clinical trials.

Clinical efficacy and safety of zoledronic acid in osteoporosis and Paget's disease

Osteoporosis and Paget’s bone disease are the most common diseases of the bone. In addition to glucocorticoid treatment, there are many other secondary causes of osteoporosis. Bisphosphonates are used to treat these bone conditions. Zoledronic acid is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least 1 year following a single intravenous administration. The efficacy and safety of zoledronic acid in the treatment of osteoporosis and Paget’s bone disease are reviewed. This article also covers the studies of the effects of zoledronic acid in the bone loss associated with the secondary osteoporosis.

Vitamin D in health and disease : an insight into traditional functions and new roles for the 'sunshine vitamin'

Vitamin D is unique among the vitamins in that humans can synthesize it via the action of UV radiation upon the skin. This combined with its ability to act on specific target tissues via Vitamin D Receptor’s (VDR) make its classification as a steroid hormone more appropriate. While Vitamin D deficiency is a recognized problem in some northern latitude countries, recent studies have shown even in sunny countries such as Australia, vitamin D deficiency may be more prevalent than first thought. Vitamin D is most well known for its role in bone health, however, the discovery of VDR’s on a wide variety of tissue types has also opened up roles for vitamin D far beyond traditional bone health. These include possible associations with autoimmune diseases such as multiple sclerosis and inflammatory bowel diseases, cancer, cardiovascular diseases and muscle strength. Firstly, this paper presents an overview of the two sources of vitamin D: exposure to ultraviolet-B radiation and food sources of vitamin D, with particular focus on both Australian and international studies on dietary vitamin D intake and national fortification strategies. Secondly, the paper reviews recent epidemiological and experimental evidence linking vitamin D and its role in health and disease for the major conditions linked to suboptimal vitamin D, while identifying significant gaps in the research and possible future directions for research.

Inequalities in cardiovascular disease mortality : the role of behavioural, physiological and social risk factors

Background: While the relationship between socioeconomic disadvantage and cardiovascular disease (CVD) is well established, the role that traditional cardiovascular risk factors play in this association remains unclear. We examined the association between education attainment and CVD mortality and the extent to which behavioural, social and physiological factors explained this relationship. Methods: Adults (n=38 355) aged 40-69 years living in Melbourne, Australia were recruited in 1990-1994. Subjects with baseline CVD risk factor data ascertained through questionnaire and physical measurement were followed for an average of 9.4 years with CVD deaths verified by review of medical records and autopsy reports. Results: CVD mortality was higher for those with primary education only compared to those who had completed tertiary education, with a hazard ratio (HR) of 1.66 (95% confidence interval [CI] 1.11-2.49) after adjustment for age, country of birth and gender. Those from the lowest educated group had a more adverse cardiovascular risk factor profile compared to the highest educated group, and adjustment for these risk factors reduced the HR to 1.18 (95% CI 0.78-1.77). In analysis of individual risk factors, smoking and waist circumference explained most of the difference in CVD mortality between the highest and lowest education groups. Conclusions: Most of the excess CVD mortality in lower socioeconomic groups can be explained by known risk factors, particularly smoking and overweight. While targeting cardiovascular risk factors should not divert efforts from addressing the underlying determinants of health inequalities, it is essential that known risk factors are addressed effectively among lower socioeconomic groups.

Development of a particle number and particle mass emissions inventory for an urban fleet : a study in South-East Queensland

Motor vehicles are a major source of gaseous and particulate matter pollution in urban areas, particularly of ultrafine sized particles (diameters < 0.1 µm). Exposure to particulate matter has been found to be associated with serious health effects, including respiratory and cardiovascular disease, and mortality. Particle emissions generated by motor vehicles span a very broad size range (from around 0.003-10 µm) and are measured as different subsets of particle mass concentrations or particle number count. However, there exist scientific challenges in analysing and interpreting the large data sets on motor vehicle emission factors, and no understanding is available of the application of different particle metrics as a basis for air quality regulation. To date a comprehensive inventory covering the broad size range of particles emitted by motor vehicles, and which includes particle number, does not exist anywhere in the world. This thesis covers research related to four important and interrelated aspects pertaining to particulate matter generated by motor vehicle fleets. These include the derivation of suitable particle emission factors for use in transport modelling and health impact assessments; quantification of motor vehicle particle emission inventories; investigation of the particle characteristic modality within particle size distributions as a potential for developing air quality regulation; and review and synthesis of current knowledge on ultrafine particles as it relates to motor vehicles; and the application of these aspects to the quantification, control and management of motor vehicle particle emissions. In order to quantify emissions in terms of a comprehensive inventory, which covers the full size range of particles emitted by motor vehicle fleets, it was necessary to derive a suitable set of particle emission factors for different vehicle and road type combinations for particle number, particle volume, PM1, PM2.5 and PM1 (mass concentration of particles with aerodynamic diameters < 1 µm, < 2.5 µm and < 10 µm respectively). The very large data set of emission factors analysed in this study were sourced from measurement studies conducted in developed countries, and hence the derived set of emission factors are suitable for preparing inventories in other urban regions of the developed world. These emission factors are particularly useful for regions with a lack of measurement data to derive emission factors, or where experimental data are available but are of insufficient scope. The comprehensive particle emissions inventory presented in this thesis is the first published inventory of tailpipe particle emissions prepared for a motor vehicle fleet, and included the quantification of particle emissions covering the full size range of particles emitted by vehicles, based on measurement data. The inventory quantified particle emissions measured in terms of particle number and different particle mass size fractions. It was developed for the urban South-East Queensland fleet in Australia, and included testing the particle emission implications of future scenarios for different passenger and freight travel demand. The thesis also presents evidence of the usefulness of examining modality within particle size distributions as a basis for developing air quality regulations; and finds evidence to support the relevance of introducing a new PM1 mass ambient air quality standard for the majority of environments worldwide. The study found that a combination of PM1 and PM10 standards are likely to be a more discerning and suitable set of ambient air quality standards for controlling particles emitted from combustion and mechanically-generated sources, such as motor vehicles, than the current mass standards of PM2.5 and PM10. The study also reviewed and synthesized existing knowledge on ultrafine particles, with a specific focus on those originating from motor vehicles. It found that motor vehicles are significant contributors to both air pollution and ultrafine particles in urban areas, and that a standardized measurement procedure is not currently available for ultrafine particles. The review found discrepancies exist between outcomes of instrumentation used to measure ultrafine particles; that few data is available on ultrafine particle chemistry and composition, long term monitoring; characterization of their spatial and temporal distribution in urban areas; and that no inventories for particle number are available for motor vehicle fleets. This knowledge is critical for epidemiological studies and exposure-response assessment. Conclusions from this review included the recommendation that ultrafine particles in populated urban areas be considered a likely target for future air quality regulation based on particle number, due to their potential impacts on the environment. The research in this PhD thesis successfully integrated the elements needed to quantify and manage motor vehicle fleet emissions, and its novelty relates to the combining of expertise from two distinctly separate disciplines - from aerosol science and transport modelling. The new knowledge and concepts developed in this PhD research provide never before available data and methods which can be used to develop comprehensive, size-resolved inventories of motor vehicle particle emissions, and air quality regulations to control particle emissions to protect the health and well-being of current and future generations.

Resilience in chronic disease : the relationships among risk factors, protective factors, adaptive outcomes, and the level of resilience in adults with diabetes

Background: There are innumerable diabetes studies that have investigated associations between risk factors, protective factors, and health outcomes; however, these individual predictors are part of a complex network of interacting forces. Moreover, there is little awareness about resilience or its importance in chronic disease in adulthood, especially diabetes. Thus, this is the first study to: (1) extensively investigate the relationships among a host of predictors and multiple adaptive outcomes; and (2) conceptualise a resilience model among people with diabetes. Methods: This cross-sectional study was divided into two research studies. Study One was to translate two diabetes-specific instruments (Problem Areas In Diabetes, PAID; Diabetes Coping Measure, DCM) into a Chinese version and to examine their psychometric properties for use in Study Two in a convenience sample of 205 outpatients with type 2 diabetes. In Study Two, an integrated theoretical model is developed and evaluated using the structural equation modelling (SEM) technique. A self-administered questionnaire was completed by 345 people with type 2 diabetes from the endocrine outpatient departments of three hospitals in Taiwan. Results: Confirmatory factor analyses confirmed a one-factor structure of the PAID-C which was similar to the original version of the PAID. Strong content validity of the PAID-C was demonstrated. The PAID-C was associated with HbA1c and diabetes self-care behaviours, confirming satisfactory criterion validity. There was a moderate relationship between the PAID-C and the Perceived Stress Scale, supporting satisfactory convergent validity. The PAID-C also demonstrated satisfactory stability and high internal consistency. A four-factor structure and strong content validity of the DCM-C was confirmed. Criterion validity demonstrated that the DCM-C was significantly associated with HbA1c and diabetes self-care behaviours. There was a statistical correlation between the DCM-C and the Revised Ways of Coping Checklist, suggesting satisfactory convergent validity. Test-retest reliability demonstrated satisfactory stability of the DCM-C. The total scale of the DCM-C showed adequate internal consistency. Age, duration of diabetes, diabetes symptoms, diabetes distress, physical activity, coping strategies, and social support were the most consistent factors associated with adaptive outcomes in adults with diabetes. Resilience was positively associated with coping strategies, social support, health-related quality of life, and diabetes self-care behaviours. Results of the structural equation modelling revealed protective factors had a significant direct effect on adaptive outcomes; however, the construct of risk factors was not significantly related to adaptive outcomes. Moreover, resilience can moderate the relationships among protective factors and adaptive outcomes, but there were no interaction effects of risk factors and resilience on adaptive outcomes. Conclusion: This study contributes to an understanding of how risk factors and protective factors work together to influence adaptive outcomes in blood sugar control, health-related quality of life, and diabetes self-care behaviours. Additionally, resilience is a positive personality characteristic and may be importantly involved in the adjustment process among people living with type 2 diabetes.