Medicine (RMH) - Research Publications
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ItemNo Preview AvailableRegulation of the endosomal SNARE protein syntaxin 7 by colony-stimulating factor 1 in macrophages(AMER SOC MICROBIOLOGY, 2008-10)Colony-stimulating factor 1 (CSF-1) is the main growth factor controlling the development of macrophages from myeloid progenitor cells. However, CSF-1 also regulates some of the key effector functions of macrophages (e.g., phagocytosis and cytokine secretion). The endosomal SNARE protein syntaxin 7 (Stx7) regulates vesicle trafficking events involved in phagocytosis and cytokine secretion. Therefore, we investigated the ability of CSF-1 to regulate Stx7. CSF-1 upregulated Stx7 expression in primary mouse macrophages; it also upregulated expression of its SNARE partners Vti1b and VAMP8 but not Stx8. Additionally, CSF-1 induced the rapid serine phosphorylation of Stx7 and enhanced its binding to Vti1b, Stx8, and VAMP8. Bioinformatics analysis and results from experiments with kinase inhibitors suggested the CSF-1-induced phosphorylation of Stx7 was mediated by protein kinase C and Akt in response to phosphatidylinositol 3-kinase activation. Based on mutagenesis studies, CSF-1 appeared to increase the binding of Stx7 to its SNARE partners by inducing the phosphorylation of serine residues in the Habc domain and/or "linker" region of Stx7. Thus, CSF-1 is a key regulator of Stx7 expression and function in macrophages. Furthermore, the effects of CSF-1 on Stx7 may provide a mechanism for the regulation of macrophage effector functions by CSF-1.
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ItemNo Preview AvailableAnemia, iron deficiency, meat consumption, and hookworm infection in women of reproductive age in northwest Vietnam(AMER SOC TROP MED & HYGIENE, 2008-03)Iron deficiency anemia poses an important public health problem for women of reproductive age living in developing countries. We assessed the prevalence of iron deficiency and anemia and associated risk factors in a community-based sample of women living in a rural province of northwest Vietnam. A cross-sectional survey, comprised of written questionnaires and laboratory analysis of hemoglobin (Hb), ferritin, transferrin receptor, and stool hookworm egg count, was undertaken, and the soluble transferrin receptor/log ferritin index was calculated. Of 349 non-pregnant women, 37.53% were anemic (Hb < 12 g/dL), and 23.10% were iron deficient (ferritin < 15 ng/L). Hookworm infection was present in 78.15% of women, although heavy infection was uncommon (6.29%). Iron deficiency was more prevalent in anemic than non-anemic women (38.21% versus 14.08%, P < 0.001). Consumption of meat at least three times a week was more common in non-anemic women (51.15% versus 66.67%, P = 0.042). Mean ferritin was lower in anemic women (18.99 versus 35.66 ng/mL, P < 0.001). There was no evidence of a difference in prevalence (15.20% versus 17.23%, P = 0.629) or intensity (171.07 versus 129.93 eggs/g, P = 0.412) of hookworm infection between anemic and non-anemic women. Although intensity of hookworm infection and meat consumption were associated with indices of iron deficiency in a multiple regression model, their relationship with hemoglobin was not significant. Anemia, iron deficiency, and hookworm infection were prevalent in this population. Intake of meat was more clearly associated with hemoglobin and iron indices than hookworm. An approach to addressing iron deficiency in this population should emphasize both iron supplementation and deworming.
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ItemNo Preview AvailableComparison of QuantiFERON-TB Gold In-Tube Test and Tuberculin Skin Test for Identification of Latent Mycobacterium tuberculosis Infection in Healthcare Staff and Association Between Positive Test Results and Known Risk Factors for Infection(CAMBRIDGE UNIV PRESS, 2009-03)OBJECTIVE: We compared a whole-blood interferon-gamma release assay (QuantiFERON-TB Gold In-Tube test, hereafter "QFT-in tube test") with a tuberculin skin test (TST) to determine which test more accurately identified latent Mycobacterium tuberculosis infection in healthcare staff. METHODS: A total of 481 hospital staff members were recruited from 5 hospitals in Melbourne, Australia. They provided information about demographic variables and tuberculosis (TB) risk factors (ie, birth or travel in a country with a high prevalence of TB, working in an occupation likely to involve contact with M. tuberculosis or individuals with TB, or being a household contact of an individual with a proven case of pulmonary TB). The QFT-in tube test and the TST were administered in accordance with standardized protocols. Concordance between the test results and positive risk factors was analyzed using the kappa statistic, the McNemar test, and logistic regression. RESULTS: A total of 358 participants had both a TST result and a QFT-in tube test result available for comparison. There were fewer positive QFT-in tube test results than positive TST results (6.7% vs. 33.0%; P<.001). Agreement between the tests was poor (71%; kappa=0.16). A positive QFT-in tube test result was associated with birth in a country with a high prevalence of TB, the number of years an individual had lived in a country with a high prevalence of TB (ie, the effect of each additional year, treated as a continuous variable), and high-risk occupational contact. A positive TST result was associated with older age, receipt of bacille Calmette-Guérin (BCG) vaccination, and working in an occupation that involved patient contact. Receipt of BCG vaccination was most strongly associated with discordant results in instances in which the TST result was positive and the QFT-in tube test result was negative. CONCLUSION: In a population of healthcare staff with a low prevalence of TB and a significant rate of BCG vaccination, a positive QFT-in tube test result was associated with the presence of known risk factors for TB exposure, whereas a positive TST result was more strongly associated with a prior history of BCG vaccination.
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ItemThe effectiveness of 4 monthly albendazole treatment in the reduction of soil-transmitted helminth infections in women of reproductive age in Viet Nam(ELSEVIER SCI LTD, 2009-07-15)Soil-transmitted helminth (STH) infections are endemic in northern Viet Nam where the climate and agricultural practices, such as the use of human excreta as fertiliser and the use of wastewater for irrigation, favour transmission. An intervention was conducted in Yen Bai Province, north-west Viet Nam, to measure the effectiveness of single dose albendazole (400mg) administered every 4 months for reducing the prevalence of STH infections in women of reproductive age. Stool samples were collected from women before the intervention and 3 and 12 months post-intervention. Information on a range of demographic and socio-economic variables was also collected to measure the major risk factors for high STH burden in this area. The prevalence of hookworm, Ascaris lumbricoides and Trichuris trichiura infection in the baseline sample of 366 women were 76.2%, 19.2% and 29.1%, respectively. In the women who were surveyed at baseline and again at 3 and 12 months after the intervention (n=118) cure rates were 71.3% for hookworm, 87.0% for A. lumbricoides and 81.4% for T. trichiura by the end of the 12 month study period (i.e. after three doses of albendazole). The main risk factor for hookworm infection was if women worked outside (odds ratio (OR)=3.2 (95% Confidence Interval (CI) 1.6-6.2), P=0.001) and the major risk factor for A. lumbricoides and T. trichiura infection was a lack of education. Low educational attainment was also the strongest risk factor for co-infection with all three species of STH (OR=7.5 (95% CI 3.4-16.4), P<0.001). The high rates of hookworm infection in this area of Viet Nam and the high cure rates for all three species of STH with 4 monthly albendazole treatment suggest that this programme should be expanded to all endemic areas in Viet Nam. The study also highlights the important contribution of education to women's health.
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ItemNo Preview AvailableBaseline Iron Indices as Predictors of Hemoglobin Improvement in Anemic Vietnamese Women Receiving Weekly Iron-Folic Acid Supplementation and Deworming(AMER SOC TROP MED & HYGIENE, 2009-12)Iron deficiency anemia is highly prevalent among women living in rural Vietnam. However, the utility and cut-offs of indices for diagnosing iron deficiency anemia in the public health context is ill defined. We assessed the ability of iron indices to predict the hemoglobin response (HBR) to weekly iron-folic acid supplementation (WIFS) in anemic rural Vietnamese women. We compared hemoglobin, serum ferritin, and soluble transferrin receptor in a cohort of 221 non-pregnant women of reproductive age before and after 3 months of WIFS and deworming. At baseline, anemia (Hb < 120 g/L) was present in 81/221 (36.7%) of subjects. After 3 months, anemia prevalence fell to 58/221 (26.2%), and the mean hemoglobin change was +3.5 g/L (95% confidence interval, 0.9, 6.6). A hemoglobin response was observed in 50/75 (66.6%) of anemic women. A ferritin cut-off < 30 ng/mL was a more sensitive predictor of response than ferritin < 15 ng/mL.
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ItemWound Chronicity, Inpatient Care, and Chronic Kidney Disease Predispose to MRSA Infection in Diabetic Foot Ulcers(AMER DIABETES ASSOC, 2009-10)OBJECTIVE: To determine the microbiological profile of diabetes-related foot infections (DRFIs) and the impact of wound duration, inpatient treatment, and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: Postdebridement microbiological samples were collected from individuals presenting with DRFIs from 1 January 2005 to 31 December 2007. RESULTS: A total of 653 specimens were collected from 379 individuals with 36% identifying only one isolate. Of the total isolates, 77% were gram-positive bacteria (staphylococci 43%, streptococci 13%). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 23%; risk factors for MRSA included prolonged wound duration (odds ratio 2.31), inpatient management (2.19), and CKD (OR 1.49). Gram-negative infections were more prevalent with inpatient management (P = 0.002) and prolonged wound duration (P < 0.001). Pseudomonal isolates were more common in chronic wounds (P < 0.001). CONCLUSIONS: DRFIs are predominantly due to gram-positive aerobes but are usually polymicrobial and increase in complexity with inpatient care and ulcer duration. In the presence of prolonged duration, inpatient management, or CKD, empiric MRSA antibiotic cover should be considered.
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ItemWeight Gain in Early Life Predicts Risk of Islet Autoimmuity in Children With a First-Degree Relative With Type 1 Diabetes(AMER DIABETES ASSOC, 2009-01)OBJECTIVE: In a prospective birth cohort study, we followed infants who had a first-degree relative with type 1 diabetes to investigate the relationship between early growth and infant feeding and the risk of islet autoimmunity. RESEARCH DESIGN AND METHODS: Infants with a first-degree relative with type 1 diabetes were identified during their mother's pregnancy. Dietary intake was recorded prospectively to determine duration of breast-feeding and age at introduction of cow's milk protein, cereals, meat, fruit, and vegetables. At 6-month reviews, length (or height) and weight, antibodies to insulin, GAD65, the tyrosine phosphatase-like insulinoma antigen, and tissue transglutaminase were measured. Islet autoimmunity was defined as persistent elevation of one or more islet antibodies at consecutive 6-month intervals, including the most recent measure, and was the primary outcome measure. RESULTS: Follow-up of 548 subjects for 5.7 +/- 3.2 years identified 46 children with islet autoimmunity. Weight z score and BMI z score were continuous predictors of risk of islet autoimmunity (adjusted hazard ratios 1.43 [95% CI 1.10-1.84], P = 0.007, and 1.29 [1.01-1.67], P = 0.04, respectively). The risk of islet autoimmunity was greater in subjects with weight z score >0 than in those with weight z score < or =0 over time (2.61 [1.26-5.44], P = 0.01). Weight z score and BMI z score at 2 years and change in weight z score between birth and 2 years, but not dietary intake, also predicted risk of islet autoimmunity. CONCLUSIONS: Weight gain in early life predicts risk of islet autoimmunity in children with a first-degree relative with type 1 diabetes.
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ItemImplantable microimagers(MDPI, 2008-05)Implantable devices such as cardiac pacemakers, drug-delivery systems, and defibrillators have had a tremendous impact on the quality of live for many disabled people. To date, many devices have been developed for implantation into various parts of the human body. In this paper, we focus on devices implanted in the head. In particular, we describe the technologies necessary to create implantable microimagers. Design, fabrication, and implementation issues are discussed vis-à-vis two examples of implantable microimagers; the retinal prosthesis and in vivo neuro-microimager. Testing of these devices in animals verify the use of the microimagers in the implanted state. We believe that further advancement of these devices will lead to the development of a new method for medical and scientific applications.
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ItemBaseline comorbidities in a population-based cohort of rheumatoid arthritis patients receiving biological therapy: data from the Australian rheumatology association database.(Hindawi Limited, 2009)Aims. To describe the baseline characteristics of an Australian population-based cohort of rheumatoid arthritis (RA) patients commencing biological therapy. Methods. Descriptive analysis from the Australian Rheumatology Association Database (ARAD). Results. Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD) age 57.0 (12.5) years). Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7%) and osteoporosis (30.4%); 61 (9.8%) had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina). Self-reported infections within the previous 6 months were common (71.5%). Conclusions. History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy.
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ItemAnkylosing spondylitis patients commencing biologic therapy have high baseline levels of comorbidity: a report from the Australian rheumatology association database.(Hindawi Limited, 2009)Aims. To compare the baseline characteristics of a population-based cohort of patients with ankylosing spondylitis (AS) commencing biological therapy to the reported characteristics of bDMARD randomised controlled trials (RCTs) participants. Methods. Descriptive analysis of AS participants in the Australian Rheumatology Association Database (ARAD) who were commencing bDMARD therapy. Results. Up to December 2008, 389 patients with AS were enrolled in ARAD. 354 (91.0%) had taken bDMARDs at some time, and 198 (55.9%) completed their entry questionnaire prior to or within 6 months of commencing bDMARDs. 131 (66.1%) had at least one comorbid condition, and 24 (6.8%) had a previous malignancy (15 nonmelanoma skin, 4 melanoma, 2 prostate, 1 breast, cervix, and bowel). Compared with RCT participants, ARAD participants were older, had longer disease duration and higher baseline disease activity. Conclusions. AS patients commencing bDMARDs in routine care are significantly different to RCT participants and have significant baseline comorbidities.