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.     

BSACI 2021 guideline for the management of egg allergy

This guideline advises on the management of patients with egg allergy. Most commonly egg allergy presents in infancy, with a prevalence of approximately 2% in children and 0.1% in adults. A clear clinical history will confirm the diagnosis in most cases. Investigation by measuring egg-specific IgE (by skin prick testing or specific IgE assay) is useful in moderate-severe cases or where there is diagnostic uncertainty. Following an acute allergic reaction, egg avoidance advice should be provided. Egg allergy usually resolves, and reintroduction can be achieved at home if reactions have been mild and there is no asthma. Patients with a history of severe reactions or asthma should have reintroduction guided by a specialist. All children with egg allergy should receive the MMR vaccine. Most adults and children with egg allergy can receive the influenza vaccine in primary care, unless they have had anaphylaxis to egg requiring intensive care support. Yellow Fever vaccines should only be considered in egg-allergic patients under the guidance of an allergy specialist. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for allergists and others with a special interest in allergy. The recommendations are evidence based. Where evidence was lacking, consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, diagnosis, treatment, prognosis and co-morbid associations.     

The Z‐plasty contributes to the coalescence of a chronic non‐healing wound

This study aimed to explore the treatment effect of Z‐plasty on a non‐healing wound. A total of 72 patients diagnosed with a chronic non‐healing wound in Peking University Third Hospital from November 2009 to August 2019 were retrospectively analysed. Among them, 27 patients were treated with Z‐plasty, and 45 patients were treated with the general method. Detailed patient information was retrieved from medical records, including age, gender, body mass index (BMI), alcohol, smoking, and comorbidities (diabetes mellitus, hypertension, heart disease). Surgical parameters included operation time and intraoperative blood loss. Wound swelling, epidermal blisters, wound edge colour, and skin temperature at 1 day after surgery were assessed to evaluate the blood supply of the wound. Surgical complications included infection, haematoma, dehiscence, and non‐healing within 2 weeks postoperatively. Student t test (for continuous data) and Chi‐square test (for categorical data) were conducted to determine the statistical difference. We found no significant differences in age, gender, BMI, alcohol, smoking, and comorbidities between the two groups. Z‐plasty did not show any advantages in the surgical time, invasive blood loss, hospital days, and hospitalisation expenses. The incidence of abnormal wound edge colour with Z‐plasty was significantly lower than that with the general treatment (P < .05), and the Z‐plasty enables better healing of the patient''s wound (P < .05). Z‐plasty promoted better recovery of chronic non‐healing wounds than direct suturing.     

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.