Thrombocytopenia in solid tumors

Thrombocytopenia in patients with solid malignancy can be caused by bone marrow involvement or toxicity from anticancer therapy; however, it could rarely be the first presentation of a tumor such as breast cancer or lymphoma. Hematological paraneoplastic syndromes such as paraneoplastic thrombocytopenia and/or immune thrombocytopenic purpura (ITP) are well described as secondary findings simultaneously with malignancies such as breast cancer and lymphoma. Other hematological conditions such as severe amegakaryocytic thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), and myelodysplastic syndromes (MDS) have also rarely been described as a possible paraneoplastic process complicating solid tumors. On the one hand, occult disseminated malignancy may mimic ITP and TTP, leading to diagnostic and therapeutic problems. On the other hand, thrombocytopenia could be the first manifestation of cancer.

Returning to work: exploring the experiences of women with acute coronary syndromes

Aims: The aim of this study was to explore the transition experiences of Australian women in resuming paid employment after an acute coronary syndrome (ACS) event. Background: Until recently cardiovascular research has focused predominantly on men but this is changing and research exploring women’s experiences of ACS has increased. Despite knowing that many women do not resume paid employment following an ACS event, little is known about the experience of those women who do, even though it is understood that returning to the previous level of employment after an ACS event is a positive outcome. Design: An exploratory qualitative approach underpinned by naturalistic inquiry was undertaken. Methods: A purposive sample of seven women who had experienced their first ACS event 12 months ago was selected. Each woman was interviewed using a semi–structured format and their interviews were transcribed verbatim. Thematic analysis of the transcript set and conceptual mapping were employed to formulate key themes. Findings: All women (mean age 52.6 years) resumed paid employment at various stages during their recovery, but reported similar transition processes. Three key themes representing this process were identified: primary motivation; influence through guidance and support; and resuming paid employment. Conclusions: Study findings revealed that these women required substantial support from family, friends and employers, with ongoing guidance from health professionals to return to paid work. The time frames for their return varied and some modified their roles within the workforce to enable them to return to paid work. However, formal cardiac rehabilitation did not appear to have a significant impact on these participants' decisions to return to work. They felt that more information about this decision may have been helpful if given at the time of cardiac rehabilitation.

The role of the granulocyte colony-stimulating factor receptor (G-CSF-R) in disease

Granulocyte colony-stimulating factor (G-CSF) is a key regulator of granulopoiesis via stimulation of a specific cell-surface receptor, the G-CSF-R, found on hematopoietic progenitor cells as well as neutrophilic granulocytes. It is perhaps not surprising, therefore, that mutations of the G-CSF-R has been implicated in several clinical settings that affect granulocytic differentiation, particularly severe congenital neutropenia, myelodysplastic syndrome and acute myeloid leukemia. However, other studies suggest that signalling via the G-CSF-R is also involved in a range of other malignancies. This review focuses on the molecular mechanisms through which the G-CSF-R contributes to disease.

Markers of inflammation in South Asian and European infants from birth to 2 years in Manchester, UK

Inflammatory markers, including serum C-reactive protein (CRP), are predictors of coronary heart disease (CHD) in adults. South Asians in the UK have higher rates of CHD in adulthood than national rates.We tested the hypotheses that South Asian infants would have higher serum concentrations of CRP and homocysteine than European infants up to 2 years of age and that higher infant weight is associated with elevation of inflammatory markers. Infants of South Asian and European origin were investigated in a mixed cross sectional-longitudinal cohort study. Mothers were recruited ante-natally from St Mary’s Hospital,Manchester by postal invitation and telephone call to non-responders. Infants with metabolic or congenital abnormalities, known syndromes or pre-maturity were excluded. Measurements were collected at birth and either 3, 6, 12 or 24 months. High sensitivity CRP and homocysteine were measured by an immulite immunoassay. We used mixed linear modelling to assess whether infant weight, ethnicity, length of follow-up or their interaction were associated with inflammatory makers in infants during follow-up. Data are presented on 306 infants (109 South Asian and 197 European). We found that European infants had higher serum CRP than South Asian infants during follow-up which was of borderline significance.There was no difference in serum homocysteine between ethnic groups during followup and no significant interaction between ethnicity and follow-up. Infant weight was significantly associated with CRP but not homocysteine. In this ongoing longitudinal study,we found little difference in inflammatory markers in infants from birth to 2 years despite markedly higher rates of CHD in South Asian than European adults. Life course exposure to risk factors may play a more dominant role in the development of CHD.

Abstracts of the Inaugural Australian Conference for Cognitive Neuropsychology and Cognitive Neuropsychiatry

The first Australian Conference for Cognitive Neuropsychology and Cognitive Neuropsychiatry was conducted by the School of Psychology at Deakin University, Geelong, from Friday, July 13 to Sunday, July 15 and was attended by over 50 cognitive psychologists, neuropsychologists and speech pathologists from Australia, New Zealand, Singapore and the UK. The Conference aimed to bring together researchers from different disciplines including linguistics, psychology, philosophy and speech pathology to present research that relates (neuropsychological or psychiatric) impairment to theories of normal cognitive functioning. The scientific program of the conference included 24 papers of exceptional quality. They were organised into the following thematic sessions: Disorders of language comprehension and production; Semantic memory and category-specific disorders; Reading: development and acquired dyslexia; Writing: development and acquired dyslexia; Memory; Object and face recognition; Theory of mind; Misidentification syndromes. Keynote speakers were Professor Andy Young from the University of York, England and Professor Max Coltheart from the Macquarie Centre for Cognitive Sciences, Sydney.

What do general practitioners think depression is? A taxonomy of distress and depression for general practice

Objective:
To create a taxonomy of distress and depression for use in primary care, that mirrors the thinking and practice of experienced general practitioners.

Design:
Qualitative study, using an ethnomethodological approach, with observation of videotaped routine GP–patient consultations and in-depth interviews with GPs.

Setting and participants:
The study was conducted in metropolitan Melbourne in 2005. Fourteen GPs conducted 36 patient consultations where depression was a focus; nine GPs participated in in-depth interviews to elicit details of how they recognised and diagnosed depression in their patients.

Results:
GPs consider distress and depression in three steps. In the first step, a change in a group of symptoms and signs is observed (eg, facial expression, loss of drive). The second step categorises the syndrome according to whether or not there is an identifiable environmental cause (reactive or “endogenous”), with the final step categorising the reactive syndromes according to their most prominent symptoms: either anxiety and worry, or helplessness and hopelessness. The resulting taxonomy includes: endogenous depression (a chronic and perhaps characterological depression characterised by a lack of interest and motivation); anxious depressive reaction (stress or worry); and hopeless depressive reaction (demoralisation).

Conclusion:
This simple and parsimonious taxonomy has validity based on its derivation from within the primary care setting.

Flowering ecology of a Box-Ironbark Eucalyptus community

Box-Ironbark forests occur on the inland hills of the Great Dividing Range in Australia, from western Victoria to southern Queensland. These dry, open forests are characteristically dominated by Eucalyptus species such as Red Ironbark E. tricarpa, Mugga Ironbark E. sideroxylon and Grey Box E. microcarpa. Within these forests, several Eucalyptus species are a major source of nectar for the blossom-feeding birds and marsupials that form a distinctive component of the fauna. In Victoria, approximately 83% of the original pre - European forests of the Box-Ironbark region have been cleared, and the remaining fragmented forests have been heavily exploited for gold and timber. This exploitation has lead to a change in the structure of these forests, from one dominated by large 80-100 cm diameter, widely -spaced trees to mostly small (≥40 cm DBH), more densely - spaced trees. This thesis examines the flowering ecology of seven Eucalyptus species within a Box-Ironbark community. These species are characteristic of Victorian Box-Ironbark forests; River Red Gum E. camaldulensis, Yellow Gum E. leucoxylon, Red Stringybark E. macrorhyncha, Yellow Box E. melliodora, Grey Box E. microcarpa, Red Box E. polyanthemos and Red Ironbark E. tricarpa. Specifically, the topics examined in this thesis are: (1) the floral character traits of species, and the extent to which these traits can be associated with syndromes of bird or insect pollination; (2) the timing, frequency, duration, intensity, and synchrony of flowering of populations and individual trees; (3) the factors that may explain variation in flowering patterns of individual trees through examination of the relationships between flowering and tree-specific factors of individually marked trees; (4) the influence of tree size on the flowering patterns of individually marked trees, and (5) the spatial and temporal distribution of the floral resources of a dominant species, E. tricarpa. The results are discussed in relation to the evolutionary processes that may have lead to the flowering patterns, and the likely effects of these flowering patterns on blossom-feeding fauna of the Box-Ironbark region. Flowering observations were made for approximately 100 individually marked trees for each species (a total of 754 trees). The flower cover of each tree was assessed at a mean interval of 22 (+ 0.6) days for three years; 1997, 1998 and 1999. The seven species of eucalypt each had characteristic flowering seasons, the timing of which was similar each year. In particular, the timing of peak flowering intensity was consistent between years. Other spatial and temporal aspects of flowering patterns for each species, including the percentage of trees that flowered, frequency of flowering, intensity of flowering and duration of flowering, displayed significant variation between years, between forest stands (sites) and between individual trees within sites. All seven species displayed similar trends in flowering phenology over the study, such that 1997 was a relatively 'poor' flowering year, 1998 a 'good' year and 1999 an 'average' year in this study area. The floral character traits and flowering seasons of the seven Eucalyptus species suggest that each species has traits that can be broadly associated with particular pollinator types. Differences between species in floral traits were most apparent between 'summer' and 'winter' flowering species. Winter - flowering species displayed pollination syndromes associated with bird pollination and summer -flowering species displayed syndromes more associated with insect pollination. Winter - flowering E. tricarpa and E. leucoxylon flowers, for example, were significantly larger, and contained significantly greater volumes of nectar, than those of the summer flowering species, such as E. camaldulensis and E. melliodom. An examination of environmental and tree-specific factors was undertaken to investigate relationships between flowering patterns of individually marked trees of E. microcarpa and E. tricarpa and a range of measures that may influence the observed patterns. A positive association with tree-size was the most consistent explanatory variable for variation between trees in the frequency and intensity of flowering. Competition from near-neighbours, tree health and the number of shrubs within the canopy area were also explanatory variables. The relationship between tree size and flowering phenology was further examined by using the marked trees of all seven species, selected to represent five size-classes. Larger trees (≥40 cm DBH) flowered more frequently, more intensely, and for a greater duration than smaller trees. Larger trees provide more abundant floral resources than smaller trees because they have more flowers per unit area of canopy, they have larger canopies in which more flowers can be supported, and they provide a greater abundance of floral resources over the duration of the flowering season. Heterogeneity in the distribution of floral resources was further highlighted by the study of flowering patterns of E. tricarpa at several spatial and temporal scales. A total of approximately 5,500 trees of different size classes were sampled for flower cover along transects in major forest blocks at each of five sample dates. The abundance of flowers varied between forest blocks, between transects and among tree size - classes. Nectar volumes in flowers of E. tricarpa were sampled. The volume of nectar varied significantly among flowers, between trees, and between forest stands. Mean nectar volume per flower was similar on each sample date. The study of large numbers of individual trees for each of seven species was useful in obtaining quantitative data on flowering patterns of species' populations and individual trees. The timing of flowering for a species is likely to be a result of evolutionary selective forces tempered by environmental conditions. The seven species' populations showed a similar pattern in the frequency and intensity of flowering between years (e.g. 1998 was a 'good' year for most species) suggesting that there is some underlying environmental influence acting on these aspects of flowering. For individual trees, the timing of flowering may be influenced by tree-specific factors that affect the ability of each tree to access soil moisture and nutrients. In turn, local weather patterns, edaphic and biotic associations are likely to influence the available soil moisture. The relationships between the timing of flowering and environmental conditions are likely to be complex. There was no evidence that competition for pollinators has a strong selective influence on the timing of flowering. However, as there is year-round flowering in this community, particular types of pollinators may be differentiated along a temporal gradient (e.g. insects in summer, birds in winter). This type of differentiation may have resulted in the co-evolution of floral traits and pollinator types, with flowers displaying adaptations that match the morphologies and energy requirements of the most abundant pollinators in any particular season. Spatial variation in flowering patterns was evident at several levels. This is likely to occur because of variation in climate, weather patterns, soil types, degrees of disturbance and biotic associations, which vary across the Box-Ironbark region. There was no consistency among sites between years in flowering patterns suggesting that factors affecting flowering at this level are complex. Blossom-feeding animals are confronted with a highly spatially and temporally patchy resource. This patchiness has been increased with human exploitation of these forests leading to a much greater abundance of small trees and fewer large trees. Blossom-feeding birds are likely to respond to this variation in different ways, depending upon diet-breadth, mobility and morphological and behavioural characteristics. Future conservation of the blossom-feeding fauna of Box-Ironbark forests would benefit from the retention of a greater number of large trees, the protection and enhancement of existing remnants, and revegetation with key species, such as E. leucoxylon, E. microcarpa and E. tricarpa. The selective clearing of summer flowering species, which occur on the more fertile areas, may have negatively affected the year-round abundance and distribution of floral resources. The unpredictability of the spatial distribution of flowering patches within the region means that all remnants are likely to be important foraging areas in some years.

Integrity of the circadian time-keeping system in chronic fatigue syndrome

Chronic Fatigue Syndrome (CFS) is a debilitating condition in which severe, ongoing fatigue is the most prominent of a complex of somatic, psychological and neuropsychological symptoms. The aetiology of CFS remains uncertain and, to date, efforts to distinguish a clear pathophysiological profile for the disorder have been unsuccessful. Current evidence suggests that, rather than being a discrete disease entity with a single cause, CFS is a clinical condition resulting from the interaction of a number of pathophysiological factors, including acute infections, stress and psychiatric disorder. Recently, there has been some interest in the proposition that disordered circadian time-keeping may contribute to the development and/or course of the illness. The rationale for the investigation of circadian factors in CFS is based on the fact that disorders known to be associated with circadian dysregulation, such as jet lag and shiftwork related syndromes have a high degree of symptomatological overlap with CFS. Also, the presence of circadian disturbance could account, in part, for other phenomenological aspects of CFS, including the high rates of comorbid affective disturbance, and the reports of low-level immune dyregulation among sufferers. While several recent studies have produced some evidence of chronobiological dysregulation in CFS patients, much work remains before conclusions can be drawn about the presence, nature and clinical significance of circadian disturbance in CFS. This thesis describes a series of studies that were designed to systematically investigate: 1. whether CFS is associated with a state of circadian dysregulation, and 2. whether circadian dysregulation contributes significantly to the symptomatology of CFS. The first of the 5 studies reported here compared the circadian patterns of sleep-activity of CFS sufferers with those of healthy controls. Results indicated that CFS patients' sleep-activity cycles were significantly phase delayed compared to controls, and that some aspects of their circadian profiles of sleep-activity were related to some measures of sleep-disturbance and well-being. Studies 2 and 3 investigated the relationship between rhythms of sleep-wake and core temperature in CFS patients and healthy controls. The major finding from these studies was that sleep-wake and core temperature rhythms appear to be less effectively synchronised. Further evidence was collected that suggested that there was a relationship between circadian parameters and symptom measures in the CFS group. While this indicated that circadian dysregulation is linked in some way to the symptoms of CFS, assessment of the actual clinical significance of circadian disturbances required the use of a prospective methodology. The final two studies, therefore, report on a placebo-controlled trial of clinical interventions that were designed to restore circadian integrity to CFS patients, in order to see whether this would lead to a reduction in symptom number or severity. Results indicated that, although patients experienced improvements across a range of measures of symptoms and functional capacity, these were small in magnitude, of unlikely clinical significance, and no greater, in general, to improvements reported by patients who underwent placebo treatment. These results, along with those of the earlier studies, are discussed with respect to their implications regarding the presence and significance of circadian dysregulation. It is concluded that, while they provide evidence that CFS is associated with a degree of both internal and external circadian desynchrony, these findings suggest that circadian dysregulation is likely to be only a peripheral, contributor to the processes that generate and maintain the symptom complex. These findings are discussed with respect to how they contribute to our overall understanding of this multi-dimensional condition, and the implications they have for the continuing effort to investigate the causes and treatment of CFS.

Self-injury and eating pathology

It was found that Urgency and lack of Perseverance were significantly elevated in women with self-injury or eating pathology, and significantly higher again in women with both these syndromes. A longitudinal design found that self-injury tends to progress from milder, compulsive forms, to more severe, impulsive forms over time. The portfolio examines the frequent co-occurrence of substance use and psychiatric disorders (Dual Diagnosis). Four primary conceptualisations of how dual diagnoses develop and present are discussed. These models are then applied to inform four case studies.

Depression and pain : an overview

Background: Depression and pain are both burdensome ailments that affect a major proportion of the population. It is evident that depression and pain frequently coexist, with treatment and outcome implications.

Objective: To review the literature on the nature, prevalence and co-morbidity of depression and pain, the biological and psychological mechanisms involved and treatment options, thus presenting a broad overview of the current information available.

Methods: Relevant sources were identified from PubMed and Medline databases using a combination of keywords including depression, pain, prevalence, co-morbidity, biological and psychological mechanisms, serotonin (5-HT), norepinephrine (NE), hypothalamic-pituitary-adrenal (HPA) axis, amygdala, functional magnetic resonance imaging (fMRI), antidepressant and psychological therapy.

Results: It is evident from the research that depression and pain are common co-morbidities. Pain as a physical symptom of depression affects approximately 65% of patients, leading to less favourable outcomes and greater health care utilization. Moreover, depression is a common feature in chronic pain patients and can affect pain threshold and tolerance. Evidence from biological and psychological studies has revealed mechanisms that link chronic pain to depression. Several classes of anti-depressants and psychological interventions have been used successfully in the treatment of somatic symptoms of depression and for a variety of pain syndromes.

Conclusions: Pain and depression are linked by overlapping phenomenology, neurobiology and therapy. They are mutually interacting, and the interaction has significant treatment and outcome implications.

Childhood sexual abuse and adolescent eating disorder : findings from the Victorian Adolescent Health Cohort study

Objective: To examine the relationship between childhood sexual abuse (CSA) before the age of 16 years and later onset of bulimia and anorexia nervosa symptoms in females.

Design: A longitudinal cohort study of adolescents observed from August 1992 to March 2003. The cohort was defined in a 2-stage cluster sample using 44 Australian schools in Victoria.

Setting: Population based.

Participants: A total of 1936 persons participated at least once and survived to the age of 24 years, including 999 females. The mean (SD) age of females at the start of follow- up was 14.91 (0.39) years; and at completion, 24.03 (0.55) years.

Main Exposure: Self-reported CSA before the age of 16 years was ascertained retrospectively at the age of 24 years.

Outcome Measures: Incident Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition)–defined partial syndromes of anorexia and bulimia nervosa were identified between waves 4 (mean age, 16.3 years) and 6 (mean age, 17.4 years) using the Branched Eating Disorder Test.

Results: The incidence of bulimic syndrome during adolescence was 2.5 (95% confidence interval, 0.80-8.0) times higher among those who reported 1 episode of CSA and 4.9 (95% confidence interval, 1.9-12.7) times higher among those who reported 2 or more episodes of CSA, compared with females reporting no episodes, adjusted for age and background factors. The association persisted after adjusting for possible confounders or mediators measured 6 months earlier, including psychiatric morbidity and dieting behavior. There was little evidence of an association between CSA and partial syndromes of incident anorexia nervosa.

Conclusion: Childhood sexual abuse seems to be a risk factor for the development of bulimic syndromes, not necessarily mediated by psychiatric morbidity or severe dieting.

Facilitating best practice : transferring the lessons of the Clinical Support Systems program

The Clinical Support Systems Program (CSSP) includes the management of clinical practice using clinical and consumer pathways, outcome and performance indicators, clinical measurement and review in a continuous improvement cycle using the best available extant evidence. The Royal Australasian College of Physicians is testing the CSSP model through four consortia around Australia. There are 17 project sites in three States. The funded projects address major clinical problems including congestive heart failure and acute coronary syndromes, acute stroke management, and colorectal cancer care. There is some early evidence of the CSSP influencing change in areas beyond the bounds of the project settings and the College has developed a plan to promote wider adoption of best practice. This approach recognises the College’s role in providing Fellows with the practical tools of quality improvement, the means to collect data and compare their practice to other clinicians, while traversing the appropriate educational framework.

Overtraining or burnout : a training and psycho-behavioural case study

The aim of this article is to present case study data that challenges the popular conception that athlete burnout represents the ultimate outcome of overtraining. A young male triathlete (22 yrs) completed a comprehensive training diary, along with the Athlete Burnout Questionnaire (ABQ) and the Multi-component Training Distress Scale (MTDS) weekly from the commencement of pre-season training, until the end of the competitive season 45 weeks later. Results were analysed retrospectively upon completion of the season and followed up with semi-structured interviews with the coach and athlete. These longitudinal observations are the first to document an athlete who appears to have simultaneously become overtrained and developed athlete burnout as measured by the ABQ. Thus we are advocating a need for future research to clarify differences between these two training-stress syndromes, specifically in relation to their aetiology, to avoid misdiagnosis and to ensure appropriate treatment for athletes experiencing these conditions is provided.