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Biomedical subjects

Christina Lee

Publications and source records attributed to Christina Lee.

At least 19 recordsLinked to original sources
PubMed2006

Influence of formulation vehicle on metronomic taxane chemotherapy: albumin-bound versus cremophor EL-based paclitaxel.

PURPOSE: Low-dose metronomic chemotherapy treatments, especially when combined with 'dedicated' antiangiogenic agents, can induce significant antitumor activity without serious toxicity in various preclinical models. It remains unclear, however, whether some cytotoxic drugs are better suited for metronomic regimens than others. Paclitaxel appears to be a strong candidate for metronomic chemotherapy given its ability to inhibit endothelial cell functions relevant to angiogenesis in vitro at extraordinarily low concentrations and broad-spectrum antitumor activity. Clinically relevant concentrations of the formulation vehicle cremophor EL in Taxol, however, were previously reported to nullify the antiangiogenic effect of paclitaxel, the result of which would hamper its usefulness in metronomic regimens. We hypothesized that ABI-007, a cremophor EL-free, albumin-bound, 130-nm form of paclitaxel, could potentially alleviate this problem. EXPERIMENTAL DESIGN: The antiangiogenic activity of ABI-007 was assessed by multiple in vitro assays. The in vivo optimal dose of ABI-007 for metronomic chemotherapy was determined by measuring circulating endothelial progenitors in peripheral blood. The antitumor effects of metronomic and maximum tolerated dose ABI-007 and Taxol were then evaluated and compared in severe combined immunodeficient mice bearing human MDA-MD-231 breast cancer and PC3 prostate cancer xenografts. RESULTS: ABI-007 significantly inhibited rat aortic microvessel outgrowth, human endothelial cell proliferation, and tube formation. The optimal metronomic dose of ABI-007 was determined to be between 3 and 10 mg/kg. Metronomic ABI-007 but not Taxol, significantly suppressed tumor growth in both xenograft models. Furthermore, the antitumor effect of minimally toxic metronomic ABI-007 approximated that of the maximum tolerated dose of Taxol. CONCLUSIONS: Our results underscore the influence of formulation vehicles on the selection of cytotoxic drugs for metronomic chemotherapy.

Albumins↗
PubMed2006

Functional assay of type I interferon in systemic lupus erythematosus plasma and association with anti-RNA binding protein autoantibodies.

OBJECTIVE: Peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) have increased expression of genes typically induced by type I interferon (IFN). However, it has been difficult to identify and quantify the factors responsible for activation of the IFN pathway in SLE. To characterize these mediators, we developed an assay that measures the functional effects of plasma or serum components on the gene expression of cultured target cells. METHODS: WISH epithelial cell line cells were cultured with medium, with recombinant IFNalpha, IFNbeta, or IFNgamma, or with 50% plasma from SLE patients (n = 73), rheumatoid arthritis (RA) patients (n = 19), or healthy donors (n = 30). Real-time quantitative polymerase chain reaction was used to determine WISH cell expression of IFN target genes, including PRKR, IFIT1, IFI44, MX1, and C1orf29 (preferentially induced by IFNalpha) and CXCL9 (Mig) (preferentially induced by IFNgamma). RESULTS: IFNalpha-regulated genes were induced by SLE plasma samples, but not by most of the RA or healthy control plasma samples. The activity in SLE plasma was inhibited >90% by anti-IFNalpha antibody, but not by anti-IFNbeta or anti-IFNgamma antibodies. The expression of each IFNalpha target gene induced by SLE plasma correlated with the expression of that gene studied ex vivo in PBMCs from the same patients and with the titer of anti-RNA binding protein (anti-RBP)-specific autoantibodies. Plasma activity paralleled PBMC expression of IFNalpha-inducible genes over time. CONCLUSION: IFNalpha in SLE plasma is a major stimulus of IFN target gene expression and is related to expression of those genes in PBMCs from SLE patients and to the titer of anti-RBP autoantibodies. These data provide additional support for the view that IFNalpha mediates immune system activation and dysregulation in SLE.

Antibodies↗
PubMed2006

Predictors and outcomes of early motherhood in the Australian Longitudinal Study on Women's Health.

Early motherhood is identified as a social problem, and having children at an early age is assumed to lead to psychological distress, welfare dependence and socioeconomic disadvantage. Analysis of responses from 9,689 young participants in the Australian Longitudinal Study on Women's Health was used to examine predictors and outcomes of early motherhood in Australia. Survey 1 (1996, aged 18 - 23) and Survey 2 (2000, aged 22 - 27), were used to categorize women as Childless, Existing Mothers (before Survey 1) and New Mothers (became mothers before Survey 2). Multivariate logistic regressions provided comparisons on sociodemographics, gynaecological variables, psychological wellbeing and health behaviours. Survey 1 data show that Existing Mothers experience socioeconomic disadvantages and unhealthy lifestyles. However, those who will go on to become mothers earlier than their peers already experience similar disadvantages. Further, the Survey 2 data show that, when these pre-existing disadvantages are controlled for, the additional deficits experienced by early mothers are relatively minor. Social disadvantage predisposes women to become mothers early, and to adopt unhealthy behaviours. However, young Australian women cope well with the challenges of early motherhood. In the longer term, unhealthy lifestyles and low education may lead to ill health and disadvantage, but early motherhood is not the initiator of this trajectory.

Adaptation, Psychological↗
PubMed2006

Predictors and correlates of coping well with early motherhood in the Australian Longitudinal Study on Women's Health.

Women who become mothers at an early age are characterised by socio-economic disadvantage and unhealthy lifestyles; however, some cope extremely well. This paper describes Australian women who become mothers at an early age, in order to identify factors that predict coping. The younger cohort of the Australian Longitudinal Study of Women's Health was used to identify 1064 young women who became mothers between Survey 1 and Survey 2. These women were categorised on the basis of the Mental Health Index of the SF-36 as having High, Normal or Low mental health. Survey 1 data were used to examine predictors, and Survey 2 data to examine correlates, of mental health. Surprisingly, few socio-demographic or health-related variables predict level of coping with early motherhood. Women who would have High mental health as mothers were likely to be in paid work, had few symptoms, and had low levels of stress. They were least likely to have a history of miscarriage and most likely to use contraception. There were no significant effects for other socio-demographic factors, or health-related behaviours. In the longer term, however, all young mothers may suffer an increasing level of disadvantage and distress relative to their peers.

Adaptation, Psychological↗
PubMed2006

Motherhood plans among young Australian women: who wants children these days?

Fertility rates in the developed world have been below replacement level for 25 years, and it is often assumed that this results from deliberate, unconstrained individual choice. Data from 7448 childless women aged 22 to 27, participating in the Australian Longitudinal Study on Women's Health, indicate that 9 per cent aspire to childlessness, with 72 per cent wanting 1 or 2 children and 19 per cent more. Differences in psychological functioning disappear after adjustment for socioeconomic variables. Women wanting 1 or 2 children also want paid work, while those wanting many children generally have traditional aspirations. Policy-makers need to consider strategies that support women to negotiate motherhood and paid work.

Adult↗
PubMed2006

Critical health psychology: who benefits?

This commentary deals with two issues raised by Hepworth. Concerning definitions, it argues that critical health psychology needs to be more explicit in defining itself as politically left-wing, and that its central defining characteristic should be that it is research and practice which aims primarily to benefit the participants, regardless of any specific method or epistemology. Concerning the value of critical health psychology, it argues that work which has improved health on a global scale and which aims to reduce inequities is being done, but not by critical psychologists, and suggests a need for more action and less rhetoric.

Behavioral Medicine↗
PubMed2006

Does timing and sequencing of transitions to adulthood make a difference? Stress, smoking, and physical activity among young Australian women.

The major changes of the transition to adulthood are argued to be stressful, and health-related behaviors such as smoking and physical activity may be adopted, consolidated, or abandoned at this time. On the other hand, research has suggested that the normative transitions of emerging adulthood, although involving considerable change, may be associated with low stress because they are perceived as both positive and normal at this life stage. This article examines relations between the timing and sequencing of life transitions and stress and health-related behaviors, focusing on the transition to young adulthood among Australian women. A total of 853 women aged 22 to 27 provided information about the timing and sequencing of 6 life transitions: moving out of home, stopping full-time education, starting full-time work, having the first live-in relationship, marriage, and motherhood-and stress, smoking, and physical activity. Most had moved out of home, stopped full-time education, and started full-time work, but only 14% had undertaken all 6 transitions. Overall, 70% of participants had made transitions "in order." Overall, the findings suggest that the relations between timing and sequencing of transitions, and indicators of health, are moderate for smoking, but small for stress and for physical activity. These effects remained after controlling for socioeconomic status of the participants' families of origin. Matching current social norms for the timing and sequencing of life changes may be of less importance for women's well-being than is commonly believed. Although the significant relations between early or "out of order" transitions and smoking are of concern, the smaller relations with stress and with sedentariness suggest that such transitions may have limited negative consequences, and support the view that individuals are active in choosing the life path that is appropriate for them and their circumstances.

Adult↗
PubMed2005

Never-married childless women in Australia: health and social circumstances in older age.

A growing proportion of women reach older age without having married or having children. Assumptions that these older women are lonely, impoverished, and high users of social and health services are based on little evidence. This paper uses data from the Older cohort of the Australian Longitudinal Study on Women's Health to describe self-reported demographics, physical and emotional health, and use of services among 10,108 women aged 73-78, of whom 2.7% are never-married and childless. The most striking characteristic of this group is their high levels of education, which are associated with fewer reported financial difficulties and higher rates of private health insurance. There are few differences in self-reported physical or emotional health or use of health services between these and other groups of older women. Compared with older married women with children, they make higher use of formal services such as home maintenance and meal services, and are also more likely to provide volunteer services and belong to social groups. Overall, there is no evidence to suggest that these women are a "problem" group. Rather, it seems that their life experiences and opportunities prepare them for a successful and productive older age.

Adult↗
PubMed2005

A comparison of the association between socioeconomic position and cardiovascular disease risk factors in three age cohorts of Australian women: findings from the Australian Longitudinal Study on Women's Health.

OBJECTIVES: To assess the associations between three measurements of socioeconomic position (SEP) -- education, occupation and ability to cope on available income -- and cardiovascular risk factors in three age cohorts of Australian women. METHODS: Cross-sectional analysis of three cohorts of Australian women aged 18-23, 45-50 and 70-75 years. RESULTS: In general, for all exposures and in all three cohorts, the odds of each adverse risk factor (smoking, obesity and physical inactivity) were lower in the most advantaged compared with the least advantaged. Within each of the three cohorts, the effects of each measurement of SEP on the outcomes were similar. There were, however, some notable between-cohort differences. The most marked differences were those with smoking. For women aged 70-75 (older), those with the highest educational attainment were more likely to have ever smoked than those with the lowest level of attainment. However, for the other two cohorts, this association was reversed, with a stronger association between low levels of education and ever smoking among those aged 18-23 (younger) than those aged 45-50 (mid-age). Similarly, for older women, those in the most skilled occupational classes were most likely to have ever smoked, with opposite findings for mid-age women. Education was also differently associated with physical inactivity across the three cohorts. Older women who were most educated were least likely to be physically inactive, whereas among the younger and mid-age cohorts there was little or no effect of education on physical inactivity. CONCLUSION: These findings demonstrate the dynamic nature of the association between SEP and some health outcomes. Our findings do not appear to confirm previous suggestions that prestige-based measurements of SEP are more strongly associated with health-related behaviours than measurements that reflect material and psychosocial resources.

Adolescent↗
PubMed2005

Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease.

OBJECTIVE: Gene-expression studies have demonstrated increased expression of interferon (IFN)-inducible genes (IFIGs) in peripheral blood mononuclear cells (PBMCs) of many patients with systemic lupus erythematosus (SLE), with a predominant effect of type I IFN. This study examined the hypothesis that increased disease severity and activity, as well as distinct autoantibody specificities, characterize SLE patients with activation of the type I IFN pathway. METHODS: Freshly isolated PBMCs from 77 SLE patients, 22 disease controls, and 28 healthy donors were subjected to real-time polymerase chain reaction for 3 IFIGs that are preferentially induced by IFNalpha, and the data were used to derive IFNalpha scores for all individuals. Expression of IFIGs was significantly higher in SLE patients compared with disease controls or healthy donors. SLE patients with high and low IFNalpha scores were compared for clinical manifestations of disease, disease severity, disease activity, serologic features, and potential confounders, by bivariate and multivariate analyses. RESULTS: SLE patients with a high IFNalpha score had a significantly higher prevalence of renal disease, a greater number of American College of Rheumatology criteria for SLE, and a higher Systemic Lupus International Collaborating Clinics damage index (SDI) score than did SLE patients with low IFNalpha scores. Patients with high scores showed increased disease activity, as measured by lower C3 levels, hemoglobin levels, absolute lymphocyte counts, and albumin levels, and a higher anti-double-stranded DNA (dsDNA) titer, erythrocyte sedimentation rate, and SLE Disease Activity Index 2000 score. The presence of antibodies specific for Ro, U1 RNP, Sm, and dsDNA, but not phospholipids, was significantly associated with a high IFNalpha score. Logistic regression analysis confirmed that renal disease, higher SDI scores, low complement levels, and presence of anti-RNA binding protein (RBP) autoantibodies were associated with a high IFNalpha score. CONCLUSION: Activation of the IFNalpha pathway defines a subgroup of SLE patients whose condition is characterized by increased disease severity, including renal disease, increased disease activity, reflected in complement activation, and autoreactivity to RBP.

Adolescent↗
PubMed2005

The impact of breast cancer on the lives of middle-aged women: results from the Australian longitudinal study of women's health.

This article investigated the impact of breast cancer (BC) in middle-aged Australian women (45-50 years). Two waves of data collected 2 years apart from a longitudinal survey of 12,177 women identified 3 groups: (a) 11,933 (98%) who reported never having had BC, (b) 181 (1.5%) who reported a diagnosis of BC at Time 1, and (c) 63 (0.5%) who reported onset of BC between Time 1 and Time 2. Repeated measures analysis of variance was used to compare the 3 groups. Women with recent onset of BC experienced significant changes across a range of functioning compared with the other 2 groups. Compared with women with no BC, women with longer established onset of BC had significantly worse health and social outcomes, but these were associated with small effect sizes. Both groups of women with BC reported less impact on mental and emotional health than on other areas of functioning.

Australia↗
PubMed2005

Emerging adulthood and patterns of physical activity among young Australian women.

The transition from adolescence to young adulthood is associated with a sharp decline in physical activity, particularly for women. This article explores the relations between physical activity status and change and status and change in four life domains: residential independence, employment status, relationship status, and motherhood. Two waves of survey data from a representative sample of 8,545 Australian women, aged 18-23 at Survey 1 and 22-27 at Survey 2, were analyzed. Cross-sectionally, physical inactivity was most strongly related to being a mother, married, and not being in the labor force. Longitudinally, decreases in physical activity were most strongly associated with moving into a live-in relationship, with getting married, and with becoming a mother. When considered in combination, women who were married with children and not employed outside the home were the most likely to be physically inactive. The data suggest that adoption of adult statuses, particularly traditional roles involving family relationships and motherhood, is associated with reductions in physical activity for these women, although it is possible that the effect is driven by socioeconomic factors associated with early transitions. The data suggest a need for interventions to promote continued physical activity among young women who cohabit or marry and among those not in the workforce, in addition to those supporting young mothers to be physically active.

Activities of Daily Living↗
PubMed2004

Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus.

OBJECTIVE: To study the contribution of interferon-alpha (IFNalpha) and IFNgamma to the IFN gene expression signature that has been observed in microarray screens of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). METHODS: Quantitative real-time polymerase chain reaction analysis of healthy control PBMCs was used to determine the relative induction of a panel of IFN-inducible genes (IFIGs) by IFNalpha and IFNgamma. PBMCs from 77 SLE patients were compared with those from 22 disease controls and 28 healthy donors for expression of IFIGs. RESULTS: Expression of IFNalpha-inducible genes was significantly higher in SLE PBMCs than in those from disease controls or healthy donors. The level of expression of all IFIGs in PBMCs from SLE patients with IFNalpha pathway activation correlated highly with the inherent responsiveness of those genes to IFNalpha, suggesting coordinate activation of that cytokine pathway. Expression of genes preferentially induced by IFNgamma was not significantly increased in SLE PBMCs compared with control PBMCs. IFNalpha-regulated gene-inducing activity was detected in some SLE plasma samples. CONCLUSION: The coordinate activation of IFNalpha-induced genes is a characteristic of PBMCs from many SLE patients, supporting the hypothesis that IFNalpha is the predominant stimulus for IFIG expression in lupus.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Violence against young Australian women and association with reproductive events: a cross-sectional analysis of a national population sample.

OBJECTIVE: This study aimed to investigate associations between violence and younger women's reproductive events using Survey 1 (1996) data of the Younger cohort of the Australian Longitudinal Study of Women's Health (ALSWH). METHODS: Multinomial regression, using composite variables for both violence and reproductive events, adjusting for socioeconomic variables and weighted for rural and remote areas. RESULTS: 23.8% of 14,784 women aged 18 to 23 years reported violence; 12.6% reported non-partner violence in the previous year; and 11.2% reported ever having had a violent relationship with a partner. Of the latter group, 43% (4.8% overall) also reported violence in the past year. Compared with women reporting no violence, women reporting partner but not recent violence (OR 2.55, 95% CI 2.10-3.09) or partner and recent violence (OR 3.96, 95% CI 3.18-4.93) were significantly more likely to have had one or more pregnancies. Conversely, having had a pregnancy (2561) was associated with an 80% increase in prevalence of any violence and a 230% increase in partner violence. Among women who had a pregnancy, having had a miscarriage or termination was associated with violence. Partner and recent violence is strongly associated with having had a miscarriage, whether alone (OR = 2.85, 95% CI 1.74-4.66), with a termination (OR = 4.60, 2.26-9.35), or with birth, miscarriage and a termination (OR = 4.12, 1.89-9.00). CONCLUSIONS AND IMPLICATIONS: Violence among young women of childbearing age is a factor for which doctors should be vigilant, well-trained and supported to identify and manage effectively.

Adolescent↗