B cells behaving badly

The pathogenesis of B-cell lymphoproliferative disorders in general and B-cell chronic lymphocytic leukaemia in particular appears to involve dysfunctional regulation of humoral and cellular immunity with the subsequent development of genetic aberrations in B cells. In theory, either component may arise de novo or may be influenced by environmental exposures including infectious agents, antigens, genotoxic chemicals, or radiation. As an intermediary within the exposure-disease continuum, monoclonal B-cell lymphocytosis may be a helpful biomarker for teasing out these various contributions to risk. This article introduces a series of papers that resulted from an International Workshop held in May 2007 entitled 'Monoclonal B-cell Lymphocytosis and Chronic Lymphocytic Leukemia: Environmental and Genetic Risk Factors'. Research efforts, such as those described in this issue, should lead to improved interventions, more predictive biomarkers, more effective treatments, and a greater appreciation of how the immune system functions over the entire human lifespan.     

Corticosteroid insensitivity in severe asthma: significance,mechanisms and aetiology

Chronic severe asthma remains a challenging clinical problem despite the availability of modern treatments. Relative corticosteroid insensitivity is present in severe asthma and may contribute to continuing disease severity. Advances in the understanding of molecular mechanisms underlying corticosteroid insensitivity may yield new therapeutic targets. Furthermore, aetiological factors for corticosteroid insensitivity have been identified and these may be amenable to modification.     

Viruses and other infections in stillbirth: what is the evidence and what should we be doing?

In Australia, as in other developed countries, approximately 40-50% of stillbirths are of unknown aetiology. Emerging evidence suggests stillbirths are often multifactorial. The absence of a known cause leads to uncertainty regarding the risk of recurrence, which can cause extreme anguish for parents that may manifest as guilt, anger or bewilderment. Further, clinical endeavours to prevent recurrences in future pregnancies are impaired by lack of a defined aetiology. Therefore, efforts to provide an aetiological diagnosis of stillbirth impact upon all aspects of care of the mother, and inform many parts of clinical decision making. Despite the magnitude of the problem, that is 7 stillbirths per 1000 births in Australia, diagnostic efforts to discover viral aetiologies are often minimal. Viruses and other difficult to culture organisms have been postulated as the aetiology of a number of obstetric and paediatric conditions of unknown cause, including stillbirth. Reasons forwarded for testing stillbirth cases for infectious agents are non-medical factors, including addressing all parents' need for diagnostic closure, identifying infectious agents as a sporadic cause of stillbirth to reassure parents and clinicians regarding risk for future pregnancies, and to reduce unnecessary testing. It is clear that viral agents including rubella, human cytomegalovirus (CMV), parvovirus B19, herpes simplex virus (HSV), lymphocytic choriomeningitis virus (LCMV), and varicella zoster virus (VZV) may cause intrauterine deaths. Evidence for many other agents is that minimal or asymptomatic infections also occur, so improved markers of adverse outcomes are needed. The role of other viruses and difficult-to-culture organisms in stillbirth is uncertain, and needs more research. However, testing stillborn babies for some viral agents remains a useful adjunct to histopathological and other examinations at autopsy. Modern molecular techniques such as multiplex PCR, allow searches for multiple agents. Now that such testing is available, it is important to assess the clinical usefulness of such testing.     

Dopaminergic Function in the Psychosis Spectrum: An [18F]-DOPA Imaging Study in Healthy Individuals With Auditory Hallucinations

Background: The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations. Methods: We compared dopamine synthesis capacity (using 6-[¹⁸F]fluoro-L-DOPA [[¹⁸F]-DOPA] positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls. Results: There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group. Conclusions: Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.     

Cognitive vulnerability in fear of flying: the role of anxiety sensitivity

Previous research has indicated that more than 50% of air travel passengers experience hypoxia above clinical threshold. This condition produces a number of aversive somatic sensations such as difficulty breathing, elevated heart rate, dizziness, etc. Because these symptoms closely resemble the somatic symptoms of anxiety, it is interesting to look into a possible relationship between hypoxia-related symptoms and fear of flying. More specifically, the aim of this study is to clarify the role of anxiety sensitivity as a cognitive vulnerability marker in this relationship. Anxiety sensitivity is the specific tendency to interpret bodily sensations as threatening or harmful. Our hypothesis is that anxiety sensitivity moderates the relationship between hypoxia-related symptoms and fear of flying. When people with high anxiety sensitivity fly and experience somatic symptoms, they will make threatening interpretations causing fear and as a possible consequence avoidance behaviour leading to flight anxiety. About 160 participants were asked to complete the Flight Anxiety Situations Questionnaire, the Flight Anxiety Modality Questionnaire and the Anxiety Sensitivity Index. Results of a moderator analysis indicated that the relationship between somatic sensations and in-flight anxiety is stronger for people with high anxiety sensitivity than for people with low anxiety sensitivity. So it seems that anxiety sensitivity does indeed function as a moderator between the experience of somatic sensations while flying and in-flight anxiety. Clinical implications are discussed, as well as suggestions for further research.