Lung function in bronchiectasis: the influence of Pseudomonas aeruginosa

Sputum isolation of Pseudomonas aeruginosa (PA) is associated with extensive disease in bronchiectasis. It is not known, however, whether infection with P. aeruginosa is the result or the cause of severe disease. We compared spirometry in patients with bronchiectasis before and after infection with P. aeruginosa, with that of patients infected by other organisms. All patients (n=12) with chronic colonization by P. aeruginosa (PA group) were studied. These were compared with other patients with bronchiectasis with no isolations of P. aeruginosa (n=37, non-PA group). In the PA group, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were lower than in the non-PA group. The PA group, however, also had lower values at the time of initial colonization with P. aeruginosa than the current values for the non-PA group. Change in FEV1 and FVC over time was faster in the PA group than in the non-PA group. Reduction of FEV1 and FVC over time in the PA group prior to P. aeruginosa colonization was intermediate, not being statistically different from either value above. Our results confirm the association of chronic P. aeruginosa colonization with poor lung function, but conclude that patients with bronchiectasis who become colonized by P. aeruginosa have poorer lung function when first colonized than those colonized by other organisms. Decline in lung function is faster in those chronically colonized by P. aeruginosa than in those colonized by other organisms. It is not clear whether chronic P. aeruginosa colonization causes an accelerated decline in lung function or whether it is simply a marker of those whose lung function is already declining rapidly.     

Regulation of ornithine decarboxylase gene expression by the Wilms' tumor suppressor WT1

The importance of ornithine decarboxylase (ODC) to cell proliferation is underscored by the complex array of cell-specific mechanisms invoked to regulate its synthesis and activity. Misregulation of ODC has severe negative consequences on normal cell function, including the acquisition of tumorigenic growth properties by cells overexpressing ODC. We hypothesize that ODC gene expression is a candidate target for the anti-proliferative function of certain tumor suppressors. Here we show that the Wilms' tumor suppressor WT1 binds to multiple sites within the human ODC promoter, as determined by DNase I protection and methylation interference assays. The expression of WT1 in transfected HCT 116, NIH/3T3 and HepG2 cells represses activity of the ODC promoter controlling expression of a luciferase reporter gene. In contrast WT1 expression enhances ODC promoter activity in SV40-transfected HepG2 cells. Both the extent of modulation of ODC gene expression and the mediating WT1 binding elements are cell specific. Constructs expressing WT1 deletion mutants implicate two regions required for repressor function, as well as an intrinsic activation domain. Understanding the regulation of ODC gene expression by WT1 may provide valuable insights into the roles of both WT1 and ODC in development and tumorigenesis.     

Familial paraganglioma

Non-secreting paragangliomas are rare tumours usually present in the head and neck. We describe an unusual case of familial paraganglioma with cranial nerve palsies. After exhaustive investigation, a vagal paraganglioma, was found and excised. The positive family history of paraganglioma was of significance, although this was only present in one of five generations. The diagnosis and management of non-secreting paragangliomas is discussed.     

The effect of calcium overdosages on the rate of eruption and periodontal ligament of lower incisor in albino rats

Thermal enhancement of cis-diamminedichloroplatinum (II) (DDP)-mediated antitumour activity and normal tissue toxicities by whole body hyperthermia were compared in a F344 rat model under different anaesthetic conditions. Whole body hyperthermia (WBH: 120 min at 41.5 degrees C) enhanced both DDP-mediated antitumour activity and toxic side-effects. Our present study shows that anaesthetics might influence the thermal enhancement ratios (TER) calculated for DDP-mediated normal tissue toxicity but did not influence the TER calculated for antitumour activity. The TER calculated for DDP-mediated antitumour activity was 2.9. As a result of the anaesthetics used, the TER calculated for kidney and gastrointestinal toxicity ranged from 1.8 to 4.5 and from 1.2 to 2.3, respectively. The TER estimated for DDP-mediated general toxicities varied between 2.9 and 4.0 for weight loss, and from 2.0 to 2.3 based on the LD50. The differential effect of anaesthetics on TER calculated for antitumour activity and normal tissue toxicity led to different therapeutic ratios. For example the therapeutic ratio for combined WBH and DDP, using kidney damage as an end-point for normal tissue damage, ranged from 0.6 (without anaesthesia) to 1.6 (using nembutal as anaesthetic). The significantly elevated platinum levels in serum, kidney, jejunum and tumour tissue after WBH treatment may explain the thermal enhancement of DDP-mediated antitumour activity and side-effects but no correlation could be found for the differences in DDP-mediated normal tissue toxicities induced by the anaesthetics.