Leukemia risk associated with low-level benzene exposure

Background: Men who were part of an Australian petroleum industry cohort had previously been found to have an excess of lympho-hematopoietic cancer. Occupational benzene exposure is a possible cause of this excess.

Methods: We conducted a case-control study of lympho-hematopoietic cancer nested within the existing cohort study to examine the role of benzene exposure. Cases identified between 1981 and 1999 (N = 79) were age-matched to 5 control subjects from the cohort. We estimated each subject's benzene exposure using occupational histories, local site-specific information, and an algorithm using Australian petroleum industry monitoring data.

Results: Matched analyses showed that the risk of leukemia was increased at cumulative exposures above 2 ppm-years and with intensity of exposure of highest exposed job over 0.8 ppm. Risk increased with higher exposures; for the 13 case-sets with greater than 8 ppm-years cumulative exposure, the odds ratio was 11.3 (95% confidence interval = 2.85-45.1). The risk of leukemia was not associated with start date or duration of employment. The association with type of workplace was explained by cumulative exposure. There is limited evidence that short-term high exposures carry more risk than the same amount of exposure spread over a longer period. The risks for acute nonlymphocytic leukemia and chronic lymphocytic leukemia were raised for the highest exposed workers. No association was found between non-Hodgkin lymphoma or multiple myeloma and benzene exposure, nor between tobacco or alcohol consumption and any of the cancers.

Conclusions: We found an excess risk of leukemia associated with cumulative benzene exposures and benzene exposure intensities that were considerably lower than reported in previous studies. No evidence was found of a threshold cumulative exposure below which there was no risk.

Alteration of GSH level, gene expression and cell transformation in NIH3T3 cells by chronic exposure to low dose of arsenic

It is well established that arsenic toxicity is postulated to be primarily due to the binding of As(III) to sulfhydryl-containing enzymes. However, the mechanism of carcinogenesis induced by arsenic is still unclear. The interaction of arsenic with GSH and related enzymes seems a very important issue regarding mechanism of arsenical induced toxicity or carcinogenesis. The purpose of this work is to investigate the effect of chronic exposure to low dose of As(III) on GSH level, gene expression and cell transformation in NIH3T3 cells. The results showed that long-term, low dose arsenic treatment makes 3T3 cell more resistant to acute arsenic treatment. There were morphology changes after long-term arsenic treatment. First, partially immortalized 3T3 cell became immortalized. In addition, the cells were doubling more quickly than the control cells and attained higher density than the control cells at confluence. Second, cells treated with 0.1 µ.M As(III) exhibited anchorage-independent growth. Arsenic could enhance GSH level at 0.5 -10 µM dose of arsenic in 24 h treatment and decrease it at 25 µM and above. In long-term treatment with low dose of arsenic, GSH levels were decreased. As(I1I) can increase both glutathione S-transferase (GST) and glutathione reductase (GR) activities at low dose (0.5-10 M), but decreased GST and GR activities at 25 M and higher dose of arsenic, while in long-term As(III) treatment, GST and GR activities are increased. Both long-term and short-term treatments with As(III) can induce GR gene expression. GPx mRNA levels were decreased both in acute and chronic arsenic treated cells. Chronic treatment with As(III) also decreased the p53 mRNA level. Taken together, our results suggest that As(III) can alter GST, GR enzyme activities as well as GSH level and related gene expression both in long-term and short-term treatment but in a different manner in different doses. Alteration of cellular GSH level by As(III) might play all important role in gene expression and arsenic induced cell transformation.

Fuzzy logic for decision support in chronic care

Computerized clinical guidelines can provide significant benefits in terms of health outcomes and costs, however, their effective computer implementation presents significant problems. Vagueness and ambiguity inherent in natural language (textual) clinical guidelines makes them problematic for formulating automated alerts or advice. Fuzzy logic allows us to formalize the treatment of vagueness in a decision support architecture. In care plan on-line (CPOL), an intranet-based chronic disease care planning system for general practitioners (GPs) in use in South Australia, we formally treat fuzziness in interpretation of quantitative data, formulation of recommendations and unequal importance of clinical indicators. We use expert judgment on cases, as well as direct estimates by experts, to optimize aggregation operators and treat heterogeneous combinations of conjunction and disjunction that are present in the natural language decision rules formulated by specialist teams.

Cognitive functioning in chronic fatigue syndrome and the role of depression, anxiety and fatigue

Objective: This study was designed to investigate the role of depression, anxiety, and fatigue in Chronic Fatigue Syndrome (CFS) sufferers' objective and subjective cognitive performance. Methods: Twenty-three CFS sufferers and 23 healthy control participants were compared on objective and subjective assessments of cognitive performance. Depression, anxiety, and fatigue were also evaluated. Results: CFS sufferers did not demonstrate any impairment in objective cognitive functioning compared to the control group, and objective performance was not related to their higher levels of depression or their level of fatigue. Depression scores only accounted for a small amount of the variance in CFS sufferers' lower subjective assessment of their cognitive performance compared to control participants. There were no differences between the groups on anxiety scores. Conclusion: The results are discussed in terms of the heterogeneity of the CFS population and the complex interaction of symptomatological factors that characterise CFS.

Overcoming the stigma of chronic illness: strategies for normalisation of a 'spoiled identity'

This paper addresses the concept of chronic illness as a socially constructed experience of stigma. The stigma of having a chronic illness affects the person's self-concept, capacity to adapt to the illness and the quality of his/her social networks. Social stigma is a delegitimising social process derived from both popular and medical views of chronic illness. Based on research into the coping strategies of a range of people with long-term, serious chronic illnesses, the paper argues that government health policies and services in Australia can best help people with chronic illness by supporting their self-help groups and community-based activities.

A contested disease state : chronic fatigue syndrome

This paper aims firstly to look at characteristics of the condition, and current issues related to the symptomatology and presentation of ME-CFS. Secondly, it identifies methodological problems in researching ME/CFS and demonstrates that the experimental approach to researching the condition can be informed by more qualitative, constructivist approaches. Thirdly, it argues that ME-CFS is a contested state whose acceptance by the medical profession requires the legitimation of a demonstrated biomedical basis

Identification and characterization of a lymphocytic Rho-GTPase effector: rhotekin-2

Rhotekin belongs to the group of proteins containing a Rho-binding domain that are target peptides (effectors) for the Rho-GTPases. We previously identified a novel cDNA with homology to human rhotekin and in this study we cloned and characterized the coding region of this novel 12-exon gene. The ORF encodes a 609 amino-acid protein comprising a Class I Rho-binding domain and pleckstrin homology (PH) domain. Cellular cDNA expression of this new protein, designated Rhotekin-2 (RTKN2), was shown in the cytosol and nucleus of CHO cells. Using bioinformatics and RTPCR we identified three major splice variants, which vary in both the Rho-binding and PH domains. Real-time PCR studies showed exclusive RTKN2 expression in pooled lymphocytes and further purification indicated sole expression in CD4^_pos T-cells and bone marrow-derived B-cells. Gene expression was increased in quiescent T-cells but negligible in activated proliferating cells. In malignant samples expression was absent in myeloid leukaemias, low in most B-cell malignancies and CD8^pos T-cell malignancies, but very high in CD4^pos/CD8^pos T-lymphoblastic lymphoma. As the Rho family is critical in lymphocyte development and function, RTKN2 may play an important role in lymphopoiesis.

Physical activity, emotional stress, sleep disturbances, and daily fluctuations in chronic fatigue symptomatology

The current study explored the relationships between physical and emotional stress and the symptomatology of chronic fatigue syndrome (CFS). Fifty-four CFS patients were studied using a longitudinal design. A self-report format was used to collect daily measures of major physical (sleep disturbance and physical activity) and emotional (subjective emotional stress level) stressors, as well as measures of levels of fatigue and secondary symptoms. The variables accounted for a moderate variance at the individual and occasion levels. Sleep disturbance and emotional stress were found to be positively associated with levels of fatigue and symptomatology, whereas physical activity was found to have a negative relationship with fatigue only. The severity of fatigue and symptoms were found to fluctuate daily in relation with the variables, indicating the complex nature of the associations.

Rationale and design of the national benchmarking and evidence-based national clinical guidelines for chronic heart failure management programs study

OBJECTIVES: The National Benchmarks and Evidence-Based National Clinical Guidelines for Heart Failure Management Programs Study is a national, multicenter study designed to determine the nature, range, and effect of interventions applied by chronic heart failure management programs (CHF-MPs) throughout Australia on patient outcomes. Its primary objective is to use these data to develop national benchmarks and evidence-based clinical guidelines and optimize their cost-effective application by reducing quality and outcome variability. DATA SOURCES/STUDY SETTING: Primary data will be collected from CHF-MP coordinators and CHF patients enrolled in these programs on a national basis. Secondary outcome data will be collected from a national morbidity record and from patients' medical records. STUDY DESIGN: Stage I of the study involves a prospective clinical audit of all CHF-MPs throughout Australia (n = 45) to determine the extent of variability in programs currently. Stage II is a prospective cross-sectional survey design enrolling 1,500 patients (average of 40 patients per program) to firstly determine the typical profile of patients being managed via a CHF-MP in Australia and, secondly, the subsequent morbidity and mortality during the 6-month follow-up. Outcome data will be subject to multivariate analysis to determine the key components of care in this regard. All study data will be then examined in the final stage of the study (III) to develop national benchmarks for the application and auditing of CHF-MPs in Australia. CONCLUSION: Variability in patient outcomes is a product of heterogeneity among CHF-MPs. The development of national benchmarks will minimize such heterogeneity and will provide a greater level of evidence for their cost-effective application.