Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis

Perforin (pfp) and interferon-gamma (IFN-gamma) together in C57BL/6 (B6) and BALB/c mouse strains provided optimal protection in 3 separate tumor models controlled by innate immunity. Using experimental (B6, RM-1 prostate carcinoma) and spontaneous (BALB/c, DA3 mammary carcinoma) models of metastatic cancer, mice deficient in both pfp and IFN-gamma were significantly less proficient than pfp- or IFN-gamma -deficient mice in preventing metastasis of tumor cells to the lung. Pfp and IFN-gamma -deficient mice were as susceptible as mice depleted of natural killer (NK) cells in both tumor metastasis models, and IFN-gamma appeared to play an early role in protection from metastasis, Previous experiments in a model of fibrosarcoma induced by the chemical carcinogen methylcholanthrene indicated an important role for NK1.1(+) T cells, Herein, both pfp and IFN-gamma played critical and independent roles in providing the host with protection equivalent to that mediated by NK1.1+ T cells, Further analysis demonstrated that IFN-gamma, but not pfp, controlled the growth rate of sarcomas arising in these mice. Thus, this is the first study to demonstrate that host IFN-gamma, and direct cytotoxicity mediated by cytotoxic lymphocytes expressing pfp independently contribute antitumor effector functions that together control the initiation, growth, and spread of tumors in mice, (C) 2001 by The American Society of Hematology.

Personality disorders in the community: a report from the Australian national survey of mental health and wellbeing

Background: The first set of aims of the present study was to determine the prevalence of personality disorders (PDs) in a nation, and gender differences in the types and numbers of PDs endorsed. The second set of aims was to establish the relationship of PD to other, non-PD disorders, physical conditions, and disability. Method: Data were obtained from the Australian National Survey of Mental Health and Wellbeing, conducted between May and August 1997. A stratified random sample of households was generated, from which all those aged 18 or over were considered potential interviewees. There were 10,641 respondents to the survey, and this represented a response rate of 78%. Each interviewee was asked 59 questions indexing specific ICD-10 PD criteria. Results: Of the total survey sample, 704 persons had at least one PD. Using weighted replicate weights, it was estimated that approximately 6.5% of the adult population of Australia have one or more PDs (lifetime prevalence). Persons with PD were more likely to be younger, male, and not married, and to have an anxiety disorder, an affective disorder, a substance use disorder, or a physical condition. They were also more likely to have greater disability than those without PD. Conclusion: The study is the first nationwide survey of mental disorders conducted within Australia. It provides an estimate of the prevalence of the various types of PD. The survey has considerable limitations, however, and these are discussed.

Hormonal factors and risk of aneurysmal subarachnoid hemorrhage - An international population-based, case-control study

Background and Purpose-Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. Methods-This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. Results-Cases and controls did not differ with regard to menstrual and reproductive history except in age at bir th of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for over use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). Conclusions-The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role fur HRT on risk of SAH in postmenopausal women.

Employee reactions to behavioural control under conditions of stress: the moderating role of self-efficacy

Extensive research conducted in the occupational stress literature has failed to provide convincing support for the stress-buffering effects of work control on employee adjustment. Drawing on research conducted in the laboratory context, it was proposed that the stress-buffering effects of work control on employee adjustment would be more marked at high, rather than low, levels of self-efficacy. In a sample of 100 customer service representatives, a significant three-way interaction among role conflict, work control and self-efficacy (measured at Time 1) was observed on (low) depersonalization (measured at Time 2). Consistent with expectations, work control reduced the negative effects of work stress on this outcome measure only for employees who perceived high levels of self-efficacy at work. In addition, there was evidence to suggest that self-efficacy moderated the main effects of work control on job satisfaction and somatic health. These findings are discussed hi terms of their theoretical contribution to the job strain model, and also in relation to workplace interventions designed to improve levels of employee adjustment.

The burden of mental disorders in Victoria, 1996

Background: Between 1998 and 1999, a burden of disease assessment was carried out in Victoria, Australia applying and improving on the methods of the Global Burden of Disease Study. This paper describes the methods and results of the calculations of the burden due to 22 mental disorders, adding 14 conditions not included in previous burden of disease estimates, Methods: The National Survey of Mental Health and Wellbeing provided recent data on the occurrence of the major adult mental disorders in Australia. Data from international studies and expert advice further contributed to the construction of disease models, describing each condition in terms of incidence, average duration and level of severity, with adjustments for comorbidity with other mental disorders. Disability weights for the time spent in different states of mental ill health were borrowed mainly from a study in the Netherlands, supplemented by weights derived in a local extrapolation exercise. Results: Mental disorders were the third largest group of conditions contributing to the burden of disease in Victoria, ranking behind cancers and cardiovascular diseases. Depression was the greatest cause of disability in both men and women. Eight other mental disorders in men and seven in women ranked among the top twenty causes of disability. Conclusions: Insufficient information on the natural history of many of the mental disorders, the limited information on the validity of mental disorder diagnoses in community surveys and considerable differences between ICD-10 and DSM-IV defined diagnoses were the main concerns about the accuracy of the estimates. Similar and often greater concerns have been raised in relation to the estimation of the burden from common non-fatal physical conditions such as asthma, diabetes and osteoarthritis. In comparison, psychiatric epidemiology can boast greater scientific rigour in setting standards for population surveys.

Attention Deficit Hyperactivity Disorder and substance use disorders: is there a causal link?

Attention-deficit hyperactivity disorder (ADHD), characterized by restless, inattentive and hyperactive behaviours, is a relatively common childhood disorder that affects approximately 5% of the general population. There has been controversy about whether ADHD increases risks of developing substance use disorders. The available evidence suggests that, in the absence of conduct disorder, ADHD is not associated with an increased risk of substance use problems in males. There is only limited evidence on the role of ADHD in the aetiology of substance use disorders among females. While ADHD has traditionally been considered as a childhood disorder, it may also occur in adults; research needs to examine the extent to which ADHD in adulthood increases the risk of substance use disorders.

Biological control of the rabbit in Australia: lessons not learned?

The story of the spread of the European rabbit across Australia, and of the two viruses used to control it, is an interesting way to look at some of the issues associated with biological control. What can be learned from the way this system developed, and what has been learned, or not learned, from the mistakes made? Here, we look at these events and examine what insights can be gained from this history.

Detecting insomnia: comparison of four self-report measures of sleep in a young adult population

The sensitivity and specificity of four self-report measures of disordered sleep - the Sleep Impairment Index (SII), the Sleep Disorders Questionnaire (SDQ), the Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS) and the Sleep-Wake Activity Inventory (SWAI) - were compared in subjects with insomnia and normal sleep. Nineteen young adult subjects met DSM-IV criteria for primary insomnia and another 19 were normal control subjects. Discriminatory characteristics of each measure were assessed using receiver operator characteristic curve analyses. Discriminatory power was maximised for each measure to produce cut-scores applicable for identification of individuals with insomnia. The DBAS, SII and SDQ psychiatric DIMS subscale were found to correlate, and discriminated well between the two groups. The SWAI nocturnal sleep subscale was not found to be an accurate discriminator. The results suggest differences in the measures in their ability to detect insomnia, and offer guidelines as to the optimal use of test scores to identify young adults suspected of insomnia.

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a cross-sectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.

Paternal age as a risk factor for psychosis and schizophrenia: Findings from Denmark, Sweden and Australia

The offspringof older fathers have an increased risk of various disorders that may be due to the accumulation of DNA mutations during spermatogenesis. Previous studies have suggested increased paternal age may be a risk factor for schizophrenia. The aim of the current study was to examine paternal age as a risk factor for schizophrenia andror psychosis. We used data from three sources: a population-based cohort studyŽDenmark., and two case-control studiesŽSweden and Australia.. In the Danish and Australian studies, we examined both psychosis and schizophrenia. In the Swedish study we examined psychosis only. After controllingfor the effect of maternal age, increased paternal age was significantly associated with increased risk of both psychosis and schizophrenia in the Danish study and of psychosis in the Swedish study. The Australian study found no association between paternal age and risk of psychosis or schizophrenia. In all three studies the relationship between paternal age and risk of disorder in the offspring was AUB-shaped. In addition to an increased risk for the offspringof older father Ž)35 years., there was a non-significant increase for the offspringof fathers aged less than 20 years. The possible role of paternally derived DNA mutations andror other psychosocial factors associated with older paternal age warrants further research. The ‘U’-shaped relationship suggests that factors other than DNA mutations may warrant consideration in this research. The Stanley Foundation supported this project.

The prevention of mental disorders in young people

The prevention of some mental disorders in young people appears to be possible. Several small and medium randomised controlled trials show that some anxiety, affective and substance-use disorders can be prevented. These trials show that the interventions are efficacious, but whether they will be effective in routine practice is not known. The evidence is sufficiently good to warrant a large community trial in which the roll-out is staged and school communties evaluated before and after the roll-out.

Human response to environmental noise: The role of perceived control

Negative impacts of noise exposure on health and performance may result in part from learned helplessness, the syndrome of deficits typically produced by exposure to uncontrollable events. People may perceive environmental noise to be uncontrollable, and several effects of noise exposure appear to parallel learned helplessness deficits. In the present socioacoustic survey (N = 1,015), perceived control over aircraft noise correlated negatively with some effects of noise (though not others). Furthermore, these effects were better predicted by perceived control than by noise level. These observational data support the claim that learned helplessness contributes to the effects of noise exposure.