The relationship between angiogenesis and the immune response in carcinogenesis and the progression of malignant disease

Recent studies have demonstrated that angiogenesis and suppressed cell- mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein- Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-α, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-α have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease. (C) 2000 Elsevier Science Ltd.

A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Emergency Health Services (EHS) : demand and service delivery models. monograph 3 : patients’ reasons and perceptions

Executive Summary Emergency health is a critical component of Australia’s health system and emergency departments (EDs) are increasingly congested from growing demand and blocked access to inpatient beds. The Emergency Health Services Queensland (EHSQ) study aims to identify the factors driving increased demand for emergency health and to evaluate strategies which may safely reduce the future demand growth. This monograph addresses the perspectives of users of both ambulance services and EDs. The research reported here aimed to identify the perspectives of users of emergency health services, both ambulance services and public hospital Emergency Departments and to identify the factors that they took into consideration when exercising their choice of location for acute health care. A cross-sectional survey design was used involving a survey of patients or their carers presenting to the EDs of a stratified sample of eight hospitals. A specific purpose questionnaire was developed based on a novel theoretical model which had been derived from analysis of the literature (Monograph 1). Two survey versions were developed: one for adult patients (self-complete); and one for children (to be completed by parents/guardians). The questionnaires measured perceptions of social support, health status, illness severity, self-efficacy; beliefs and attitudes towards ED and ambulance services; reasons for using these services, and actions taken prior to the service request. The survey was conducted at a stratified sample of eight hospitals representing major cities (four), inner regional (two) and outer regional and remote (two). Due to practical limitations, data were collected for ambulance and ED users within hospital EDs, while patients were waiting for or under treatment. A sample size quota was determined for each ED based on their 2009/10 presentation volumes. The data collection was conducted by four members of the research team and a group of eight interviewers between March and May 2011 (corresponding to autumn season). Of the total of 1608 patients in all eight emergency departments the interviewers were able to approach 1361 (85%) patients and seek their consent to participate in the study. In total, 911 valid surveys were available for analysis (response rate= 67%). These studies demonstrate that patients elected to attend hospital EDs in a considered fashion after weighing up alternatives and there is no evidence of deliberate or ill-informed misuse. • Patients attending ED have high levels of social support and self-efficacy that speak to the considered and purposeful nature of the exercise of choice. • About one third of patients have new conditions while two thirds have chronic illnesses • More than half the attendees (53.1%) had consulted a healthcare professional prior to making the decision. • The decision to seek urgent care at an ED was mostly constructed around the patient’s perception of the urgency and severity of their illness, reinforced by a strong perception that the hospital ED was the correct location for them (better specialised staff, better care for my condition, other options not as suitable). • 33% of the respondent held private hospital insurance but nevertheless attended a public hospital ED. Similarly patients exercised considered and rational judgements in their choice to seek help from the ambulance service. • The decision to call for ambulance assistance was based on a strong perception about the severity of the illness (too severe to use other means of transport) and that other options were not considered appropriate. • The decision also appeared influenced by a perception that the ambulance provided appropriate access to the ED which was considered most appropriate for their particular condition (too severe to go elsewhere, all facilities in one spot, better specialised and better care). • In 43.8% of cases a health care professional advised use of the ambulance. • Only a small number of people perceived that ambulance should be freely available regardless of severity or appropriateness. These findings confirm a growing understanding that the choice of professional emergency health care services is not made lightly but rather made by reasonable people exercising a judgement which is influenced by public awareness of the risks of acute health and which is most often informed by health professionals. It is also made on the basis of a rational weighing up of alternatives and a deliberate and considered choice to seek assistance from a service which the patient perceived was most appropriate to their needs at that time. These findings add weight to dispensing with public perceptions that ED and ambulance congestion is a result of inappropriate choice by patients. The challenge for health services is to better understand the patient’s needs and to design and validate services that meet those needs. The failure of our health system to do so should not be grounds for blaming the patient, claiming inappropriate patient choices.

Community health workers' response to violence against women

This paper reports on a qualitative study of community health workers from a predominantly rural based region in Queensland. The purpose of this study was to determine the community health worker barriers to identification, assessment and intervention on the issue of violence against women. The qualitative research method comprised five structured focus group interviews with 28 community health workers using open-ended questions to explore their perceptions. Analysis of the focus group data revealed that community health workers expressed reluctance to become involved in cases of violence against women. The reasons they provided are grouped under three main themes: barriers to identification; barriers to assessment; and barriers to intervention. Training programs offered to rural community health workers need to be aware of the barriers to identifying, assessing and intervening in cases of violence against women that are highlighted by this study. Further studies are needed to assess the wider relevance of these findings to other groups of community health workers in rural and non-rural settings.

Better prepared next time : considering nutrition in an emergency response

To the Editor: Cyclones, floods and bushfires are experienced in Australia every year, and Australia’s management of natural disasters centres on prevention, preparedness, response and recovery.1 Although access to safe food is a basic human need, during the 2010–2011 Queensland floods there was minimal information available to guide household food preparedness and food supply to communities...

Beyond the ‘three dogmas of juvenile justice’ : a response to Weatherburn, McGrath and Bartels

In 'Three Dogmas of Juvenile Justice', Weatherburn, McGrath and Bartels identify three 'assumptions' or 'dogmas' about youth justice, on which they claim 'juvenile justice policy in Australia currently rests'.

Factors influencing health professionals' response to victims of domestic violence

This thesis examined factors influencing health professional's response to victims of domestic violence in Vietnam. As this is the first time that this type of research has been conducted in Vietnam, it was expected that the results would contribute significantly to local knowledge and should add to global perspectives. Since it is the first questionnaire about this topic to be developed in Vietnam, the psychometric property of the questionnaire was primarily established, resulting in the questionnaire being recommended to use for further study. By explaining the factors that affect the intentions to respond of health workers, this project provides key data for authorities to design intervention strategies to improve the responses of health professionals to victims of domestic violence in Vietnam.

Screening for youth depression in schools : a review of the literature

This paper provides a review of the literature pertaining to screening for youth depression in schools. It provides the rationale regarding this topic – why this topic is important and needs to be explored. This justification is followed by an investigation of the importance of mental health intervention in general – including depression. Analysis will then shift to the current literature surrounding screening for youth depression in schools, followed by additional information relating to this topic.

Role of electromechanical wave propagation in power systems

In a large interconnected power system, disturbances initiated by a fault or other events cause acceleration in the generator rotors with respect to their synchronous reference frame. This acceleration of rotors can be described by two different dynamic phenomena, as shown in existing literature. One of the phenomena is simultaneous acceleration and the other is electromechanical wave propagation, which is characterized by travelling waves in terms of a wave equation. This paper demonstrates that depending on the structure of the system, the exhibited dynamic response will be dominated by one phenomenon or the other or a mixture of both. Two system structures of choice are examined, with each structure exemplifying each phenomenon present to different degrees in their dynamic responses. Prediction of dominance of either dynamic phenomenon in a particular system can be determined by taking into account the relative sizes of the values of its reduced admittance matrix.

A novel real time pricing scheme for demand response in residential distribution systems

Price based technique is one way to handle increase in peak demand and deal with voltage violations in residential distribution systems. This paper proposes an improved real time pricing scheme for residential customers with demand response option. Smart meters and in-home display units are used to broadcast the price and appropriate load adjustment signals. Customers are given an opportunity to respond to the signals and adjust the loads. This scheme helps distribution companies to deal with overloading problems and voltage issues in a more efficient way. Also, variations in wholesale electricity prices are passed on to electricity customers to take collective measure to reduce network peak demand. It is ensured that both customers and utility are benefitted by this scheme.

Fiction as a form of change : a paper overview of a literature panel discussion

It is well established that literary work can promote insights that result in future change, whether on a personal or an institutional level. As Umberto Eco (1989) notes, the act of reading does not stop with the artist but continues into the work of communities. The papers delivered in this panel consider the regenerative role of literature within culture, arguing that the special properties of literature can convey an important sense of nature (Bateson 1973, Zapf 2008). These concepts are discussed in relation to writing about Australian flora and fauna. Using an ecocritical focus based on ideas about the relationship between literature and the environment the paper considers Australian works and the way in which literature enlivens this complex intersection between humans, animals and the environment. This engagement is investigated through three modes: the philosophical, the literary, and the practical. The novels discussed include Alexis Wright’s Carpentaria, Richard Flanagan’s Wanting, and Sonya Hartnett’s Forest, as well as a range of fictional and non-fictional works that describe the Blue Mountains region in New South Wales. The paper closes with a discussion of the role of story-telling as a way of introducing the public to specific environmental locations and issues.

Shadow boxing with an imaginary enemy : a response to "Law and Order Blues"

In our rejoinder to Don Weatherburn's paper,"Law and Order Blues", we do not take issue with his advocacy of the need to take crime seriously and to foster a more rational approach to the problems it poses. Where differences do emerge is (1) with his claim that he is willing to do so whilst we (in our different ways) are not; and (2) on the question of what this involves. Of particular concern is the way in which his argument proceeds by a combination of simple misrepresentation of the positions it seeks to disparage, and silence concerning issues of real substance where intellectual debate and exchange would be welcome and useful. Our paper challenges, in turn, the misrepresentation of Indermaur's analysis of trends in violent crime, the misrepresentation of Hogg and Brown's Rethinking Law and Order, the misrepresentation of the findings of some of the research into the effectiveness of punitive policies and the silence on sexual assault in "Law and Order Blues". We suggest that his silence on sexual assault reflects a more widespread unwillingness to acknowledge the methodological problems that arise in the measurement of crime because such problems severely limit the extent to which confident assertions can be made about prevalence and trends.

Literature review : use of respite by carers of people with dementia

Respite care is a cornerstone service for the home management of people with dementia. It is used by carers to mitigate the stress related to the demands of caring by allowing time for them to rest and do things for themselves, thus maintaining the caring relationship at home and perhaps forestalling long-term placement in a residential aged care facility. Despite numerous anecdotal reports in support of respite care, its uptake by carers of people with dementia remains relatively low. The aim of this paper was to examine the factors that constitute the use of respite by carers of people with dementia by reviewing quantitative and qualitative research predominantly from the years 1990 to 2012. Seventysix international studies of different types of respite care were included for this review and their methods were critically appraised. The key topics identified were in relation to information access, the barriers to carers realising need for and seeking respite, satisfaction with respite services including the outcomes for carers and people with dementia, the characteristics of an effective respite service and the role of health workers in providing appropriate respite care. Finally, limitations with considering the literature as a whole were highlighted and recommendations made for future research.

No sex difference in body fat in response to supervised and measured exercise

It is often reported that females lose less body weight than males do in response to exercise. These differences are suggested to be a result of females exhibiting a stronger defense of body fat and a greater compensatory appetite response to exercise than males do. Purpose This study aimed to compare the effect of a 12-wk supervised exercise program on body weight, body composition, appetite, and energy intake in males and females. Methods A total of 107 overweight and obese adults (males = 35, premenopausal females = 72, BMI = 31.4 ± 4.2 kg·m−2, age = 40.9 ± 9.2 yr) completed a supervised 12-wk exercise program expending approximately 10.5 MJ·wk−1 at 70% HRmax. Body composition, energy intake, appetite ratings, RMR, and cardiovascular fitness were measured at weeks 0 and 12. Results The 12-wk exercise program led to significant reductions in body mass (males [M] = −3.03 ± 3.4 kg and females [F] = −2.28 ± 3.1 kg), fat mass (M = −3.14 ± 3.7 kg and F = −3.01 ± 3.0 kg), and percent body fat (M = −2.45% ± 3.3% and F = −2.45% ± 2.2%; all P < 0.0001), but there were no sex-based differences (P > 0.05). There were no significant changes in daily energy intake in males or females after the exercise intervention compared with baseline (M = 199.2 ± 2418.1 kJ and F = −131.6 ± 1912.0 kJ, P > 0.05). Fasting hunger levels significantly increased after the intervention compared with baseline values (M = 11.0 ± 21.1 min and F = 14.0 ± 22.9 mm, P < 0.0001), but there were no differences between males and females (P > 0.05). The exercise also improved satiety responses to an individualized fixed-energy breakfast (P < 0.0001). This was comparable in males and females. Conclusions Males and premenopausal females did not differ in their response to a 12-wk exercise intervention and achieved similar reductions in body fat. When exercise interventions are supervised and energy expenditure is controlled, there are no sex-based differences in the measured compensatory response to exercise.

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake

BACKGROUND/OBJECTIVEs A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI). SUBJECTS/METHODS Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m2) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m2). RESULTS Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (−102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=−0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=−0.44; P=0.01). CONCLUSIONS Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.