BackgroundAs supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures.MethodsA systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 μg) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal.ResultsAt baseline, all nine patients had normal responses to 1 μg ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively.ConclusionImmediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test.

Background: Evaluating the importance of the different sources of variations is essential in microarray data experiments. Complex experimental designs generally include various factors structuring the data which should be taken into account. The objective of these experiments is the exploration of some given factors while controlling other factors.

Integration of functional genomics from small bronchoscopic biopsies allows molecular tumor classification and prediction of survival in NSCLC and might become a powerful adjunct for the daily clinical practice.

Results: After MCA-SSH and DS, 117 clones from a total of 1000 were selected for sequence analysis. Four genes were identified in the DNA fragments from 117 clones from A/J mouse lung tumor tissue. These were KIF21A (kinesin family member 21A), Samd14 (sterile alpha motif domain containing 14), EG436235 (similar to regulator of G-protein signal 3) and Vwa1 (von Willebrand factor A domain containing 1). Among these four genes, two gene fragments had a genomic region that met the criteria for a CpG island. RT-PCR showed differences in expression level between A/J mouse normal lung tissue and lung adenoma tissue for the KIF21A (p<0.005), Samd14 (p=0.005) and EG436235 (p<0.01) genes. Further study of the human homologues of KIF21A (p<0.01) and Samd14 (p<0.002) showed that they were expressed in normal lung tissue but markedly down-regulated in lung adenocarcinoma tissue. Bisulfite sequencing revealed that the promtor region of Samd14 in human lung adenocarcinoma was methylated more frequently than that of its normal counterpart. Conclusions:The expression level of the KIF21A (location: 12q12) and Samd14 (location: 17q21.33) genes is down regulated in human pulmonary adenocarcinoma tissue. The methylation frequency of the Samd14 gene in the promotor region is higher in human pulmonary adenocarcinoma than in normal lung tissue. These data suggest that promotor methylation of these genes is a specific event in pulmonary adenocarcinogenesis, and that their down-regulation may be functionally associated with malignant progression of lung adenocarcinoma B7-03 BSTB: Molecular Diagnostics & Pathology, Tue, 13:45 -15:30

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