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Biomedical subjects

Karen Anderson

Publications and source records attributed to Karen Anderson.

At least 19 recordsLinked to original sources
PubMed2006

Use of research by the Australian health promotion workforce.

This paper examines the attitudes and practices of Australian health promotion practitioners toward evidence-based practice (EBP). The study used a survey methodology and questionnaires were sent to 1114 members of the Australian Health Promotion Association. A response rate of 27% (n = 277) was achieved. The data showed that the vast majority of participant's attitudes toward EBP was very welcoming. However, in practice the impact of EBP was limited. Participants identified a range of significant barriers to implementing EBP including organizational culture, policy directives and lack of resources. A range of concerns was also identified regarding the applicability of the medically based EBP model within health promotion, which is based upon a social model of health. The findings highlight the importance of acknowledging the complexity of health promotion interventions and working toward developing an appropriate evidence base.

Adult↗
PubMed2006

PtdIns3P binding to the PX domain of p40phox is a physiological signal in NADPH oxidase activation.

The production of reactive oxygen species by the NADPH oxidase complex of phagocytes plays a critical role in our defence against bacterial and fungal infections. The PX domains of two oxidase components, p47(phox) and p40(phox), are known to bind phosphoinositide products of PI3Ks but the physiological roles of these interactions are unclear. We have created mice which carry an R58A mutation in the PX domain of their p40(phox) gene, which selectively prevents binding to PtdIns3P. p40(phoxR58A/R58A) embryos do not develop normally but p40(phoxR58A/-) mice are viable and neutrophils from these animals exhibit significantly reduced oxidase responses compared to those from their p40(phox+/-) siblings (e.g. 60% reduced in response to phagocytosis of Staphylococcus aureus). Wortmannin inhibition of the S. aureus oxidase response correlates with inhibition of phagosomal PtdIns3P accumulation and overlaps with the reduction in this response caused by the R58A mutation, suggesting PI3K regulation of this response is substantially dependent on PtdIns3P-binding to p40(phox). p40(phoxR58A/-) mice are significantly compromised in their ability to kill S. aureus in vivo, defining the physiological importance of this interaction.

Amino Acid Sequence↗
PubMed2006

Probability of obsessive and compulsive symptoms in Huntington's disease.

BACKGROUND: The purpose of this study was to examine the probability of obsessive and compulsive (OC) symptoms across stages of Huntington's disease (HD) with both cross sectional and longitudinal data. METHODS: We present the largest sample to date of individuals at risk for HD (N = 3964). Obsessive and compulsive symptoms were assessed with the Unified Huntington's Disease Rating Scale OC items. RESULTS: The probability of meeting the threshold for obsessions and compulsions increased with greater disease severity. Those with no motor abnormalities ("at risk") had a 7% probability of obsessions and a 3.5% probability of compulsions; the peak probability for obsessions (24%) and compulsions (12%) occurred in patients with advanced disease with significant functional disability. CONCLUSIONS: The probability of OC symptoms is more than three times greater by stages 3 and 4 (clearly manifest disease) than in our at-risk group with no apparent motor abnormalities.

Adult↗
PubMed2006

IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis.

OBJECTIVE: The IKK complex regulates NF-kappaB activation, an important pathway implicated in the rheumatoid arthritis (RA) disease process. This study was undertaken to assess the efficacy of N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)-2-methylnicotinamide (ML120B), a potent and selective small molecule inhibitor of IKKbeta. METHODS: Polyarthritis was induced in rats by injection of Freund's complete adjuvant into the hind footpad. ML120B was administered orally twice daily, either prophylactically or therapeutically. Paw volumes and body weights were measured every 2-3 days throughout the study. We assessed bone erosions by several methods: histologic evaluation, quantitative micro-computed tomography (micro-CT) imaging analysis, and measurement of type I collagen fragments in the serum. Quantitative polymerase chain reaction was used to evaluate expression of messenger RNA for genes related to inflammation and to bone and cartilage integrity. RESULTS: Oral administration of ML120B inhibited paw swelling in a dose-dependent manner (median effective dosage 12 mg/kg twice daily) and offered significant protection against arthritis-induced weight loss as well as cartilage and bone erosion. We were able to directly demonstrate that NF-kappaB activity in arthritic joints was reduced after ML120B administration. Also, we observed that down-regulation of the NF-kappaB pathway via IKKbeta inhibition dampened the chronic inflammatory process associated with rat adjuvant-induced arthritis. CONCLUSION: The results of the present study suggest that IKKbeta inhibition is an effective therapeutic approach to treat both the inflammation and the bone/cartilage destruction observed in RA. Methods for the determination of serum markers for bone and cartilage destruction, as well as micro-CT analysis, may aid in predicting and evaluating the therapeutic efficacy of IKKbeta inhibition therapy in humans.

Animals↗
PubMed2006

Mice deficient in PKC theta demonstrate impaired in vivo T cell activation and protection from T cell-mediated inflammatory diseases.

In the present study we have characterized T cell-driven immune function in mice that are genetically deficient in PKC theta. In response to simple immunologic stimulation invoked by in vivo T cell receptor (TCR) cross-linking, these mice showed significantly depressed plasma cytokine levels for IL-2, IL-4, IFNgamma, and TNFalpha compared to wild-type (WT) mice. In parallel, spleen mRNA levels for these cytokines were reduced, and NF-kappaB activation was also reduced in PKC theta knockouts (KO). Injection of allogeneic cells into the footpad of PKC theta deficient mice provoked a significantly diminished local T cell response compared to WT mice similarly challenged. Unlike comparable cells from wild type mice, CD45RBhi T cells harvested from PKC theta deficient mice failed to induce colitis in the SCID-CD45RB cell transfer model of IBD. In another T cell-dependent model of inflammatory disease, PKC theta deficient animals developed far less severe neurologic signs and reduced spinal cord inflammatory cell infiltrate compared to WT controls in the MOG-induced EAE model. A fundamental role for PKC theta in T cell activation and in the development of T cell-mediated inflammatory diseases is indicated by these results.

Animals↗
PubMed2005

Evaluation of diabetes care in the Otago region using a diabetes register, 1998-2003.

AIM: To assess changes in diabetes care between 1998 and 2003 using data from the Otago Diabetes Register. METHODS: A regional diabetes register was established in 1998 to monitor diabetes care in the Otago region, New Zealand. Cross-sectional data relating to process and outcome measures were collected annually from participating general practices, 93% of general practitioners in the region. Generalised estimating equations with robust standard errors were used to test for trends in clinical measures across the study period. RESULTS: Process measures improved dramatically over the 6-year period. The proportion of patients prescribed ACE inhibitors and other antihypertensives increased markedly (32.3-52.4% and 13.2-27.1%, respectively) and both mean systolic and diastolic blood pressure decreased significantly (140.6-137.0 mmHg, p < 0.001 and 78.6-77.0 mmHg, p < 0.001, respectively). The proportion prescribed lipid lowering medication more than trebled (12.4-40.0%), while mean lipid levels improved significantly (total cholesterol: 5.94-5.21 mmol/l, p < 0.001, HDL-cholesterol: 1.23-1.28 mmol/l, p < 0.001 and triglycerides: 2.17-1.94 mmol/l, p < 0.001). Mean weight increased significantly, as did HbA1c in all treatment groups except type 2 diabetic patients treated with combined insulin and oral hypoglycaemic agents. CONCLUSIONS: At a population level appreciable improvements in blood pressure and lipid control were observed, but not glycaemic control, probably due to insufficient attention to necessary lifestyle changes.

Aged↗
PubMed2005

A human phase 1 vaccine clinical trial of the Plasmodium falciparum malaria vaccine candidate apical membrane antigen 1 in Montanide ISA720 adjuvant.

A dose escalating, placebo-controlled phase 1 trial was conducted to test the safety and immunogenicity of a vaccine containing recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated in Montanide ISA720. Three groups of volunteers were vaccinated intramuscularly with 5 microg, 20 microg or 80 microg of AMA1, respectively, in 0.5 mL of formulation at 0, 3 and 6 months. Anti-AMA1 antibody levels and T cell stimulation indices were measured before and after each vaccination. No vaccine-related serious adverse events were recorded. Most subjects generated a mild to moderate, transient local reaction after the first vaccination. Three subjects developed a local reaction approximately 10 days following vaccination. Six of the 29 subjects seroconverted. Only one of these developed a high antibody titre. However, the interpretation of this trial was compromised by a loss of potency of the formulated vaccine during the course of the study.

Adjuvants, Immunologic↗
PubMed2005

The influence of primary caregivers on the sexual behavior of early adolescents.

PURPOSE: To describe rates of sexual intercourse initiation, anticipated level of sexual activity in the next 12 months, and other risk behaviors among fifth graders and to examine parental factors associated with such behaviors. METHODS: This study is based on a cross-sectional, self-administered survey conducted with a nonrandom sample of 408 fifth graders and their caregivers. Children answered questions regarding sexual intercourse initiation, anticipated sexual activity in the next 12 months, and involvement in other risk behaviors. Caregivers answered questions about parenting factors such as monitoring behaviors, parent-child relationship quality, and parent-child communication. Bivariate and multivariable analyses examined the association of these variables with the adolescents' behaviors. RESULTS: Almost 5% of girls and 17% of boys reported they had engaged in sexual intercourse. Only 34% of girls and 13% of boys said they did not expect to engage in any type of sexual contact in the next 12 months if they were going with someone they "liked a lot." Parental factors associated with fewer risk behaviors and expected sexual behaviors included higher levels of monitoring, fewer communication barriers, less permissive attitudes regarding adolescent sexual behavior, higher relationship quality with child, having fewer than five children in the household, higher levels of education, and being employed. Significant gender interactions were found for several variables. CONCLUSIONS: Adolescents are initiating sexual intercourse at extremely young ages. To delay early sexual activity and prevent adolescent pregnancy, prevention efforts must begin during the elementary school years and include those who raise and care for the adolescent.

Adolescent↗
PubMed2004

Eprosartan improves cardiac performance, reduces cardiac hypertrophy and mortality and downregulates myocardial monocyte chemoattractant protein-1 and inflammation in hypertensive heart disease.

OBJECTIVE: The purpose of this investigation was to determine whether angiotensin II receptor (AII1R) antagonism interferes with cardiac monocyte chemoattractant protein-1 (MCP-1) expression in hypertrophic cardiomyopathy and failure. DESIGN: We studied the effects of the AII1R antagonist eprosartan on MCP-1 expression, and on the recruitment of macrophages into the myocardium in a model of cardiac hypertrophy and morbidity/mortality. METHODS: Stroke-prone spontaneously hypertensive rats fed a high-salt, high-fat diet (SFD) developed heart failure characterized by left ventricular (LV) hypertrophy/pathology and hypocontractility. These rats received either normal diet, SFD, or SFD with the daily administration of 30 mg/kg eprosartan for 28 weeks. LV function and wall thickness was assessed by echocardiography, MCP-1 expression was measured by TaqMan real-time polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry, and macrophage infiltration into the LV was determined by microscopy. RESULTS: Eprosartan reduced the rate of morbidity/mortality (P = 0.001), LV MCP-1 mRNA (P < 0.05) and protein expression (P < 0.01), and LV macrophage infiltration (P < 0.01), while preserving ventricular function (P < 0.05). Eprosartan also produced a moderate (16%; P < 0.05) decrease in blood pressure. CONCLUSIONS: These data demonstrate that AII1R antagonism in an animal model of hypertensive heart disease reduces MCP-1 expression in the myocardium that results in reduced macrophage recruitment. These effects parallel the preservation of LV systolic function and the reduction in cardiac remodeling/disease progression and reduced morbidity/mortality. Suppression of MCP-1 expression might explain in part the beneficial effects of AII1R antagonism in this model.

Acrylates↗
PubMed2004

Quantitative analysis of micro-CT imaging and histopathological signatures of experimental arthritis in rats.

Micro-computed tomographic (micro-CT) imaging provides a unique opportunity to capture 3-D architectural information in bone samples. In this study of pathological joint changes in a rat model of adjuvant-induced arthritis (AA), quantitative analysis of bone volume and roughness were performed by micro-CT imaging and compared with histopathology methods and paw swelling measurement. Micro-CT imaging of excised rat hind paws (n = 10) stored in formalin consisted of approximately 600 30-mum slices acquired on a 512 x 512 image matrix with isotropic resolution. Following imaging, the joints were scored from H&E stained sections for cartilage/bone erosion, pannus development, inflammation, and synovial hyperplasia. From micro-CT images, quantitative analysis of absolute bone volumes and bone roughness was performed. Bone erosion in the rat AA model is substantial, leading to a significant decline in tarsal volume (27%). The result of the custom bone roughness measurement indicated a 55% increase in surface roughness. Histological and paw volume analyses also demonstrated severe arthritic disease as compared to controls. Statistical analyses indicate correlations among bone volume, roughness, histology, and paw volume. These data demonstrate that the destructive progression of disease in a rat AA model can be quantified using 3-D micro-CT image analysis, which allows assessment of arthritic disease status and efficacy of experimental therapeutic agents.

Animals↗
PubMed2004

A comparison of family history of psychiatric disorders among patients with early- and late-onset Alzheimer's disease.

OBJECTIVE: Both early-onset Alzheimer's Disease (EOAD) and late-onset Alzheimer's Disease (LOAD) present with cognitive and psychiatric features. Some studies suggest that EOAD patients are more likely than LOAD patients to have psychiatric symptoms. If this is true, relatives of EOAD patients with a similar clinical presentation may be more likely to be misclassified as having a primary noncognitive psychiatric disorder rather than a dementing disorder. Family history studies may underestimate familial aggregation of EOAD. METHODS: The authors compared the presence of psychiatric symptoms in parents and siblings of 131 EOAD patients (diagnosed at or before age 60), with the parents and siblings of 131 LOAD patients (diagnosed at or after age 65). Early onset Alzheimer's Disease and LOAD patients were matched for diagnosis (probable versus possible AD), gender, and ethnic group. Logistic regression analysis was performed on the outcome variable of patient group (EOAD, LOAD) with family history of psychiatric symptoms as the risk factor, adjusting for family size and patient's education. RESULTS: There was a nearly two and one-half-fold increase in family history of psychiatric symptoms among EOAD patients when compared with LOAD patients (RR = 2.4; 95% C.I. 1.2-4.7). CONCLUSIONS: The authors found preliminary evidence of a higher prevalence of a history of psychiatric symptoms among relatives of EOAD patients when compared to LOAD patients. This may be due to differential misclassification of AD, a syndromic disorder with both noncognitive psychiatric and cognitive deficits in relatives of EOAD patients. Alternatively, shared genetic or other familial etiologies may underlie subtypes of EOAD and some psychiatric disorders.

Age of Onset↗
PubMed2004

Flexible client-driven in-home case management: an option to consider.

Changes in health services and care needs have created high demand for case management of in-home services. To address this challenge, several models of case management have been used. Evaluations to date suggest that clients need different approaches for different circumstances at different times to optimize cost-effectiveness. Accordingly, one Canadian home care program adopted flexible client-driven case management engaging clients as partners in flexibly selecting either an integrated team, consumer-managed or brokerage model of case management in keeping with their preferences and abilities. Using an exploratory, multimeasure quasi-experimental design, a generic model of program evaluation, and both quantitative and qualitative methods, researchers identified challenges in implementing this intervention, policy impediments the clients characteristically in each of the three case management models, and client, provider, and caregiver outcomes of flexible, client-driven care. While further longitudinal investigation is needed findings suggest several important considerations for those interested in this option for care management. Alternative case management models do attract different client groups, and having a choice does not alter care costs or outcomes. Flexible client-driven case management may be experienced positively by case managers and other providers.

Aged↗
PubMed2003

Functional evidence that vascular endothelial growth factor may act as an autocrine factor on human podocytes.

Vascular endothelial growth factor (VEGF) is expressed by renal glomerular epithelial cells (podocytes) and is thought to be protective against nephrotoxic agents. VEGF has been shown to be an autocrine survival factor in neuropilin-1-positive, VEGF receptor-negative breast carcinoma cells. Normal human podocytes are also known to express neuropilin-1, VEGF, and are VEGF-R2 negative. Here, we investigated whether a similar VEGF autocrine loop may exist in podocytes. Podocyte cytosolic calcium concentration ([Ca(2+)](i)) was analyzed in primary cultured and conditionally immortalized podocytes using ratiometric fluorescence measurement. Cytotoxicity was determined by lactate dehydrogenase assay, proliferation by [(3)H]-thymidine incorporation, and cell counts by hemocytometric assay. VEGF decreased [Ca(2+)](i) in primary podocytes (from 179 +/- 36 to 121 +/- 25 nM, P < 0.05) and conditionally immortalized podocytes (from 95 +/- 10 to 66 +/- 8 nM, P < 0.02) in the absence of extracellular calcium. The type III receptor tyrosine-kinase inhibitor PTK787/ZK222584 abolished this reduction. VEGF increased podocyte [(3)H]-thymidine incorporation (3,349 +/- 283 cpm, control 2,364 +/- 301 cpm, P < 0.05) and cell number (4.5 +/- 0.7 x 10(4)/ml, control 2.6 +/- 0.5 x 10(4)/ml, P < 0.05) and decreased cytotoxicity (5.9 +/- 0.7%, control 12 +/- 3%, P < 0.05), whereas a monoclonal antibody to VEGF increased cytotoxicity. Electron microscopy of normal human glomeruli demonstrated that the glomerular VEGF is mostly podocyte cell membrane associated. These results indicate that one of the functions of VEGF secreted from podocytes may be to act as an autocrine factor on calcium homeostasis and cell survival.

Adult↗
PubMed2003

Stopping the active intervention: CARET.

The Carotene and Retinol Efficacy Trial (CARET) was a large, multicenter randomized chemoprevention trial designed to test a combined lung cancer prevention agent in heavy smokers and workers exposed to asbestos. In January 1996, the CARET Steering Committee decided to stop the intervention due to an adverse effect. This paper describes the decision process used to apply the stopping rules and the activities engaged in by CARET participants and staff to implement the decision. The most important activity was to draft and mail a letter to the participants informing them of the disappointing CARET results and asking them to stop taking the study vitamins and to return any unused study vitamins. The steering committee, with the support of the National Cancer Institute, planned to follow participants for disease endpoints and smoking behavior for 5 years. These activities led to smooth closure of active intervention and maintained high retention rates during the transition.

Asbestos↗
PubMed2002

Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum.

BACKGROUND: The ability of T cells, acting independently of antibodies, to control malaria parasite growth in people has not been defined. If such was shown to be effective, an additional vaccine strategy could be pursued. Our aim was to ascertain whether or not development of cell-mediated immunity to Plasmodium falciparum blood-stage infection could be induced in human beings by exposure to malaria parasites in very low density. METHODS: We enrolled five volunteers from the staff at our research institute who had never had malaria. We used a cryopreserved inoculum of red cells infected with P falciparum strain 3D7 to give them repeated subclinical infections of malaria that we then cured early with drugs, to induce cell-mediated immune responses. We tested for development of immunity by measurement of parasite concentrations in the blood of volunteers by PCR of the multicopy gene STEVOR and by following up the volunteers clinically, and by measuring antibody and cellular immune responses to the parasite. FINDINGS: After challenge and a extended period without drug cure, volunteers were protected against malaria as indicated by absence of parasites or parasite DNA in the blood, and absence of clinical symptoms. Immunity was characterised by absence of detectable antibodies that bind the parasite or infected red cells, but by the presence of a proliferative T-cell response, involving CD4+ and CD8+ T cells, a cytokine response, consisting of interferon gamma but not interleukin 4 or interleukin 10, induction of high concentrations of nitric oxide synthase activity in peripheral blood mononuclear cells, and a drop in the number of peripheral natural killer T cells. INTERPRETATION: People can be protected against the erythrocytic stage of malaria by a strong cell-mediated immune response, in the absence of detectable parasite-specific antibodies, suggesting an additional strategy for development of a malaria vaccine

Animals↗