Shake rattle and roll: a journey with Parkinson's

This is the journey of a man suffering from Parkinson's disease. Ross Collins tells of his past twelve years' experiences of living with Parkinson's. Before, he had a steady job with Victoria Police, with promising future prospects; and was happily married with two young children. The disease struck him at an early age, changing his life and setting him on a different course. His outlook on life has changed, and his decision-making influenced; as well, his relationships with his family affected. He feels normal only when he is shaking, rattling and rolling along on his Harley. His wish for a cure leads him to pin his hopes on faith healing by the 'miracle man', in Brazil. The first two visits did not seem to have done anything to improve his physical condition. Ross is returning to Brazil for the third time, hoping against hope that his condition could be improved by a miracle healing. This documentary gives an intimate look into the life of a Parkinson's disease sufferer and that of his family. Includes al.

Importance of assessing family dysfunction in conjunction with standardised measures when treating substance abuse

In this thesis, the link between substance abuse and family dysfunction is examined, and an argument is made for the assessment of family dysfunction when treating clients with substance abuse issues. Family dysfunction has been associated with a broad range of problems in children (e.g., low self esteem, increased risk of child abuse) through to adolescence and adulthood (e.g., increased risk of mental disorders such as depressive disorders, substance abuse disorders, and personality disorders) (Kaplan & Sadock, 1998). It is not the purpose of this thesis to suggest that family dysfunction causes substance abuse but rather to highlight that family dysfunction can in some cases place the individual at greater risk of substance abuse. Therefore, in order to understand the reasons why substance abuse developed and how it is maintained in the present requires the assessment of family dysfunction. Further, the importance of assessing the role and impact that family dysfunction may have had on the client, may help to better understand the nature and extent of substance abuse so that relevant and appropriate treatment goals for change may be set, progress monitored, and risk of relapse reduced. Chapter 1 provides a brief introduction to this thesis, and Chapter 2 is a review of the literature on the impact of family dysfunction including poor parental attachment and supervision, neglect, physical and sexual abuse, in adolescence and adulthood. Four case studies are presented to illustrate how family dysfunction and substance abuse may be related, thus highlighting the importance of assessing family dysfunction when treating substance abuse clients. All of the case studies include an individual with a substance abuse disorder (namely heroin) but they are diverse in terms of the types and extent of family dysfunction. The final chapter discusses the case studies in relation to the literature reviewed. Lastly, it gives consideration to the implication of a history of family dysfunction, and how it may impact negatively on treatment and therefore prognosis.

Effects of survivin antagonists of growth of established tumors and B7-1 immunogene therapy

Background: Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is detectable in most types of cancer, and its presence is associated with a poor prognosis. We determined the effects of gene-based therapies that inhibit survivin function in a mouse tumor model. Methods: Using five to six mice per treatment group, we injected tumors derived from mouse EL-4 thymic lymphoma cells with plasmids encoding antisense survivin, a dominant-negative mutant survivin, and the T-cell costimulator B7-1. Expression of endogenous survivin and the proteins encoded by the injected plasmids were examined by immunohistochemical staining of tumor sections and by western blot and flow cytometry analyses of isolated tumor cells. Tumor growth, the generation of antitumor cytotoxic T-lymphocyte (CTL) activity, apoptosis, and the contribution of leukocyte subsets to antitumor activity were measured. All statistical tests were two-sided. Results: Large (1.0-cm diameter) tumors had approximately 10-fold more survivin than small (0.2-cm diameter) tumors. At 28 days after injection, antisense and dominant-negative mutant survivin plasmids statistically significantly inhibited the growth of both small (P = .006 and P = .0018, respectively) and large (P<.001 for both plasmids) EL-4 tumors compared with tumors injected with empty plasmid. The growth of large tumors was further inhibited by intratumoral injection with antisense survivin and B7-1 (P = .004); thus, inhibition of survivin expression renders large tumors susceptible to B7-1-mediated immunotherapy. Mice whose tumors were completely eradicated by injection of B7-1 remained tumor free for 26 days after re-injection with EL-4 cells (when the experiment ended). Compared with tumors injected with empty plasmid, tumors injected with survivin-based plasmids had increased apoptosis, and animals bearing such tumors generated more antitumor CTLs. Conclusion: Intratumoral injection of plasmids that block survivin expression and stimulate the generation of tumor-specific CTLs may be beneficial for the treatment of large lymphomas.

Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic progression in transitional cell carcinoma of the bladder

Muscle invasive transitional cell carcinoma (TCC) of the bladder is associated with a high frequency of metastasis, resulting in poor prognosis for patients presenting with this disease. Models that capture and demonstrate step-wise enhancement of elements of the human metastatic cascade on a similar genetic background are useful research tools. We have utilized the transitional cell carcinoma cell line TSU-Pr1 to develop an in vivo experimental model of bladder TCC metastasis. TSU-Pr1 cells were inoculated into the left cardiac ventricle of SCID mice and the development of bone metastases was monitored using high resolution X-ray. Tumor tissue from a single bone lesion was excised and cultured in vitro to generate the TSU-Pr1-B1 subline. This cycle was repeated with the TSU-Pr1-B1 cells to generate the successive subline TSU-Pr1-B2. DNA profiling and karyotype analysis confirmed the genetic relationship of these three cell lines. In vitro, the growth rate of these cell lines was not significantly different. However, following intracardiac inoculation TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2 exhibited increasing metastatic potential with a concomitant decrease in time to the onset of radiologically detectable metastatic bone lesions. Significant elevations in the levels of mRNA expression of the matrix metalloproteases (MMPs) membrane type 1-MMP (MT1-MMP), MT2-MMP and MMP-9, and their inhibitor, tissue inhibitor of metalloprotease-2 (TIMP-2), across the progressively metastatic cell lines, were detected by quantitative PCR. Given the role of MT1-MMP and TIMP-2 in MMP-2 activation, and the upregulation of MMP-9, these data suggest an important role for matrix remodeling, particularly basement membrane, in this progression. The TSU-Pr1-B1/B2 model holds promise for further identification of important molecules.

Australia's venture capital industry : past performance, present structure and future prospects

A brief history of the Australian venture capital (VC) industry to April 2001 precedes critique of the current industry framework. This focuses on two questions: What has history taught us? and How well does the Australian VC industry enable entrepreneurship in the Australian economy? The answers embrace suggestions for better encouragement of entrepreneurship through research-based VC industry enhancement. A positive prognosis is based on a case history. A knowledgeable private citizen significantly influenced the passage of legislation vital to the industry. This success indicates the practical importance that a future program of structured research might have for the development of venture capital and entrepreneurship in Australia.

Mirror neuron dysfunction in autism spectrum disorders

Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system has been suggested as a disturbance linked to the disorder. Mirror neurons (MNs) are visuomotor neurons which discharge both when performing and observing a goal directed action. Research suggests MNs may have a role in imitation, empathy, theory of mind and language. Although the research base is small, evidence from functional MRI, transcranial magnetic stimulation, and an electroencephalographic component called the mu rhythm suggests MNs are dysfunctional in subjects with ASD. These deficits are more pronounced when ASD subjects complete tasks with social relevance, or that are emotional in nature. Promising research has identified that interventions targeting MN related functions such as imitation can improve social functioning in ASDs. Boosting the function of MNs may improve the prognosis of ASDs, and contribute to diagnostic clarity.

Recent advances in anti-survivin treatments for cancer

Apoptosis occurs via extrinsic or intrinsic signalling each triggered and regulated by many different molecular pathways. In recent years, the selective induction of apoptosis through survivin in tumour cells has been increasingly recognized as a promising approach for cancer therapy. Survivin has multiple functions including cytoprotection, inhibition of cell death, and cell-cycle regulation, especially at the mitotic process stage, all of which favour cancer survival. Many studies on clinical specimens have shown that survivin over expression is invariably up regulated in human cancers, associated with resistance to chemotherapy or radiation therapy, and linked to poor prognosis, suggesting that cancer cells survive with survivin. On the basis of these findings, survivin has been proposed as an attractive target for new anticancer interventions. Survivin inhibitors recently entered clinical trials. Recent studies suggest a possible role for survivin in regulating the function of normal adult cells. However, the expression and function of survivin in normal tissues are still not well characterized and understood. Still better understandings of survivin's role in tumour versus normal cells are needed for designing the strategies to selectively disrupt survivin in cancers. In the present review, we summarise the importance of recent survivin-targeted cancer therapy for future clinical application.

The relationship between depression and cardiovascular disease

Evidence from epidemiological studies has established that depression is a risk factor for the development of cardiovascular disease (CVD) and that the comorbidity of depression with pre-existing CVD worsens the prognosis for sufferers of CVD. Depression has also been associated with other behaviours that impact on CVD, such as medication non-compliance, and an unwillingness to adopt an exercise program, that reduce the likelihood of successful rehabilitation from CVD. Published literature on the current knowledge of the association between depression and CVD is reviewed in this paper.

Psychometric properties of a scale to measure investment in the sick role : the Illness Cognitions Scale

Rationale, aims and objectives A person’s beliefs about their illness may contribute to recovery and prognosis. Some degree of acceptance of illness and its impact is necessary to integrate the presence of a chronic disorder into one’s lifestyle and adhere to necessary components of illness management; however, some individuals can become ‘stuck’ and have difficulty adjusting out of the sick role. Inventories exist to measure illness cognitions, attitudes and behaviours as they relate to hypochondria and psychosomatic illness, but there is no extant measure of sick role inertia.We describe the psychometric properties of a new scale, the Illness Cognitions Scale (ICS), a metric of investment in the sick role.

Methods The ICS was administered to 97 individuals with bipolar or schizoaffective disorder, and the psychometric properties of the scale measured. Dimensionality was assessed using Principal Components Analysis with Oblimin rotation.

Results The scale has a strong internal consistency, with a Cronbach’s alpha of 0.858. Results of a factor analysis suggested the presence of one main factor, with three other smaller, related sub-factors, capturing aspects of maladaptive illness beliefs.

Conclusion The ICS is a 17-item, internally validated scale measuring difficulty adjusting out of the sick role. The scale predominantly measures a single construct. Further research on external validity of the ICS is required as well as determination of the clinical significance and patient acceptability of the scale.

Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention

Objective: The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention.

Methods: Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed. Individuals were categorized as having had 0, 1–5, 6–10, or >10 prior episodes of illness, and data were analyzed across these groups.

Results: Response rates for the mania and maintenance studies ranged from 52–69% and 10–50%, respectively, for individuals with 1–5 previous episodes, and from 29–59% and 11–40% for individuals with >5 previous episodes. These rates were significantly higher for the 1–5 group on most measures of response with up to a twofold increase in the chance of responding for those with fewer previous episodes. For the depression studies, response rates were significantly higher for the 1–5 group for two measures only. In the maintenance studies, the chance of relapse to either mania or depression was reduced by 40–60% for those who had experienced 1–5 episodes or 6–10 episodes compared to the >10 episode group, respectively. This trend was statistically significant only for relapse into mania for the 1–5 episode group (p = 0.005).

Conclusion: Those individuals at the earliest stages of illness consistently had a more favourable response to treatment. This is consistent with the staging model and

Evidence and implications for early intervention in bipolar disorder

Aims: To review the evidence that supports early intervention in the treatment of bipolar disorder.

Background: Bipolar disorder is a pleomorphic condition, with varying manifestations that are determined by a number of complex factors including the ‘‘stage’’ of illness. It is consequently a notoriously difficult illness to diagnose and as a corollary is associated with lengthy delays in recognition and the initiation of suitable treatment.

Methods: A literature search was conducted using MEDLINE augmented by a manual search.

Results: Emerging neuroimaging data suggests that, in contrast to schizophrenia, where at the time of a first-episode of illness there is already discernible volume loss, in bipolar disorder, gross brain structure is relatively preserved, and it is only with recurrences that there is a sequential, but marked loss of brain volume. Recent evidence suggests that both pharmacotherapy and psychotherapy are more effective if instituted early in the course of bipolar disorder, and that with multiple episodes and disease progression there is a noticeable decline in treatment response.

Conclusions: Such data supports the notion of clinical staging, and the tailored implementation of treatments according to the stage of illness. The progressive nature of bipolar disorder further supports the concept that the first episode is a period that requires energetic broad-based treatment, with the hope that this could alter the temporal trajectory of the illness. It also raises hope that prompt treatment may be neuroprotective and that this perhaps attenuates or even prevents the neurostructural and neurocognitive changes seen to emerge with chronicity. This highlights the need for early identification at a population level and the necessity of implementing treatments and services at a stage of the illness where prognosis is optimal.

Physical activity among cancer survivors : a literature review

Aim Physical activity offers a variety of health benefits to cancer survivors, both during and post-treatment. The aim here is to review: the preferences of cancer survivors regarding exercise counselling and participation in a physical activity programme; adherence rates among cancer survivors to physical activity programmes; and predictors of adherence to exercise training.

Methods Two electronic databases, Ovid MEDLINE(R) 1950 to Present with Daily Update and SCOPUS, were used to undertake literature searches for studies examining exercise preferences of adult cancer survivors, and physical activity programmes for adults at any point of the cancer trajectory.

Results Studies suggest that, while physical activity levels are low among cancer survivors, most are interested in increasing their participation. Preferences and adherence to physical activity programmes differ across a range of demographic, medical, and behavioural variables, suggesting the importance of tailoring exercise programmes to patient-specific and disease-specific needs.

Conclusions Current evidence supports the benefits of physical activity for improving risk factors associated with cancer prognosis. Physical activity programmes developed for oncology patients and cancer survivors need to take into account the needs of the target population in order to optimise adherence, outcomes, and long-term behavioural changes in this population.

Application of an Adaptive Neural Network to Medical Decision Support

Medical diagnostic and prognostic problems are prime examples of decision making in the face of uncertainty. In this paper, we investigate the applicability of the Fuzzy ARTMAP neural network as an intelligent decision support system in clinical medicine. In particular, Fuzzy ARTMAP is employed as a predictive model for prognosis of complications in patients admitted to the Coronary Care Units. A number of off-line and on-line experiments have been conducted with various network parameter settings, training methods, and learning rules. The results are compared with those from other systems including the logistic regression model. In addition, the outcomes of a set of on-line learning experiments revealed the potential of employing Fuzzy ARTMAP as an autono-mously learning system that is able to learn perpetually and, at the same time, to provide useful decision support.