Alveolar macrophages are sentinels of murine pulmonary homeostasis following inhaled antigen challenge.

BACKGROUND: Alveolar macrophages are sentinels of the pulmonary mucosa and central to maintaining immunological homeostasis. However, their role in governing the response to allergen is not fully understood. Inappropriate responses to the inhaled environment manifest as asthma. METHODS: We utilized a mechanistic IL-13-driven model and a house dust mite allergen mucosal sensitization model of allergic airway disease to investigate the role of alveolar macrophages in regulating pulmonary inflammation. RESULTS: IL-13-dependent eosinophilic and Th2 inflammation was enhanced in mice depleted of alveolar macrophages using clodronate liposomes. Similarly, depletion of alveolar macrophages during house dust mite sensitization or established disease resulted in augmented Th2 immunity and increased allergen-specific IgG1 and IgE. Clodronate treatment also delayed the resolution of tissue inflammation following cessation of allergen challenge. Strikingly, tissue interstitial macrophages were elevated in alveolar macrophage-deficient mice identifying a new homeostatic relationship between different macrophage subtypes. A novel role for the macrophage-derived immunoregulatory cytokine IL-27 was identified in modulating Th2 inflammation following mucosal allergen exposure. CONCLUSIONS: In summary, alveolar macrophages are critical regulators of Th2 immunity and their dysregulation promotes an inflammatory environment with exacerbation of allergen-induced airway pathology. Manipulating IL-27 may provide a novel therapeutic strategy for the treatment of asthma.

Quality standards for DNA sequence variation databases to improve clinical management under development in Australia.

Despite the routine nature of comparing sequence variations identified during clinical testing to database records, few databases meet quality requirements for clinical diagnostics. To address this issue, The Royal College of Pathologists of Australasia (RCPA) in collaboration with the Human Genetics Society of Australasia (HGSA), and the Human Variome Project (HVP) is developing standards for DNA sequence variation databases intended for use in the Australian clinical environment. The outputs of this project will be promoted to other health systems and accreditation bodies by the Human Variome Project to support the development of similar frameworks in other jurisdictions.

Obesity in Auckland school children: a comparison of the body mass index and percentage body fat as the diagnostic criterion.

OBJECTIVES: First, to determine obesity rates in Auckland school children according to their ethnic group using two different criteria: the body mass index (BMI) and percentage body fat (PBF) derived from bioelectrical impedance analysis (BIA). Second to examine the relationship between BMI and body composition across ethnic groups to determine if BMI references from European children accurately reflect obesity in other ethnic groups. DESIGN: A total of 2273 Auckland school children, aged 5-10.9 y had their height, weight and bioelectrical impedance measured. Using these measurements, each child's BMI, fat free mass, fat mass and PBF were derived. RESULTS: In all 14.3% of children were obese using the recommended definition of obesity (BMI) greater than the 95th percentile). There was no clinically significant difference in the relationship between BMI and body composition in different ethnic groups. Obesity rates varied with ethnicity (P<0.0001) and were higher in Pacific Island (24.1%) and Maori (15.8%) than in European children (8.6%). Obesity rates also varied with age (P<0.03), with the highest rates in older children. PBF levels were higher in females than males (P<0.0001). Using a definition of obesity based on percentage body fat (PBF>30%), obesity rates were higher in all ethnic groups. CONCLUSIONS: Obesity rates are high in Auckland school children and there are clear differences in obesity rates in different ethnic groups. If BMI criteria are used to define obesity in our population, we recommend the same standards be used for children of all ethnicities.

Foot-to-foot bioelectrical impedance analysis: a valuable tool for the measurement of body composition in children.

OBJECTIVE: To determine the accuracy of foot-to-foot bioelectrical impedance analysis (BIA) and anthropometric indices as measures of body composition in children. DESIGN: Comparison of foot-to-foot BIA and anthropometry to dual-energy X-ray absorptiometry (DEXA)-derived body composition in a multi-ethnic group of children. SUBJECTS: : Eighty-two European, NZ Maori and Pacific Island children aged 4.9-10.9 y. MEASUREMENTS: DEXA body composition, foot-to-foot bioelectrical impedance, height, weight, hip and waist measurements. RESULTS: Using a BIA prediction equation derived from our study population we found a high correlation between DEXA and BIA in the estimation of fat-free mass (FFM), fat mass (FM) and percentage body fat (PBF) (r=0.98, 0.98 and 0.94, respectively). BIA-FFM underestimated DEXA-FFM by a mean of 0.75 kg, BIA-FM overestimated DEXA-FM by a mean of 1.02 kg and BIA-PBF overestimated DEXA-PBF by a mean of 2.53%. The correlation between six anthropometric indices (body mass index (BMI), ponderal index, Chinn's weight-for-height index, BMI standard deviation score, weight-for-length index and Cole's weight-for-height index) and DEXA were also examined. The correlation of these indices with PBF was remarkably similar (r=0.85-0.87), more variable with FM (r=0.77-0.94) and poor with FFM (r=0.41-0.75). CONCLUSIONS: BIA correlated better than anthropometric indices in the estimation of FFM, FM and PBF. Foot-to-foot BIA is an accurate technique in the measurement of body composition.

Ten years' experience of persistent hyperinsulinaemic hypoglycaemia of infancy.

OBJECTIVE: To review the presentation, management and outcome of persistent hyperinsulinaemic hypoglycaemia of infancy seen at the Royal Alexandra Hospital for Children over a 10 year period. METHODOLOGY: A retrospective review of 20 subjects was performed. As well as laboratory data, data were collected on clinical presentation, medical and surgical management and developmental outcome. RESULTS: Twenty subjects (11 male) were identified with presentation at a median age of 1.5 months (range 0-10 months), with 10 (50%) presenting in the first week of life. Only 20% of patients were large for gestational age. Diagnosis was made on the basis of high glucose requirements and inappropriately high insulin levels at the time of hypoglycaemia. Eight (40%) responded well to diazoxide treatment alone, seven (35%) received diazoxide in combination with other short-term medical therapy initially and five (25%) required pancreatectomy (repeat surgery in three). Those who required surgery had a higher mean birth weight. Infants presenting in the first week of life were less likely to respond to diazoxide. At the time of last review, eight (40%) of those treated medically had ceased all treatment. Two of the five cases requiring pancreatectomy now require insulin treatment. Neurodevelopmental assessment was normal in 11 (55%), mild delay was found in six (30%) and moderate or severe delay was found in three (15%). CONCLUSIONS: Persistent hyperinsulinaemic hypoglycaemia of infancy remains a major diagnostic and management challenge. Early suspicion and recognition is critical with definitive investigation and medical therapy to avoid hypoglycaemia, with pancreatectomy in medically unresponsive cases. Normal neurodevelopmental outcome was found in only 55% of cases.

A case of chronic myelomonocytic leukemia with isochromosome 14q.

A 72-year-old man with increased monocytes and eosinophils in the bone marrow was found to have an isochromosome, i(14q), as the sole abnormality on bone-marrow cytogenetics. Follow-up over 12 months with repeat cytogenetic testing of bone marrow specimens on three further occasions showed an additional abnormality consisting of an apparently balanced translocation, t(6;21)(p21.1; q22). This abnormality, together with other features, indicated disease progression. A review of seven reported cases of i(14q) revealed limited follow-up information.