Inadequate environmental monitoring around offshore oil and gas platforms on the Grand Bank of Eastern Canada: are risks to marine birds known?

Petroleum exploration and production on the Grand Bank of eastern Canada overlaps with productive marine habitat that supports over 40 million marine birds annually. Environmental assessments for oil and gas projects in the region predict insignificant adverse effects on marine birds from oil spills, incineration in platform flares and collisions. Limited baseline data on seasonal occupancies and a failure to quantify the nature and extent of marine bird attraction to platforms and related mortality undermines these assessments. We conducted 22 surveys to offshore platforms on the Grand Bank during 1999-2003 to measure avian associations with platforms and to determine the level of monitoring needed to assess the risks to marine birds. We document seasonal shifts in marine bird occurrences and higher densities of auks (fall) and shearwaters (summer) around platforms relative to surrounding areas. The limited temporal and spatial coverage of our surveys is more robust than existing industry monitoring efforts, yet it is still inadequate to quantify the scale of marine bird associations with platforms or their associated mortality risks. Systematic observations by independent biologists on vessels and platforms are needed to generate reliable assessments of risks to marine birds. Instead, the regulatory body for offshore oil and gas in eastern Canada (Canada - Newfoundland and Labrador Offshore Petroleum Board; C-NLOPB) supports industry self-reporting as the accepted form of environmental monitoring. Conflicting responsibilities of oil and gas regulatory agencies for both energy development and environmental monitoring are major barriers to transparency, unbiased scientific inquiry and adequate environmental protection. Similar conflicts with the oil and gas regulatory body in the United States, the former Minerals and Management Service (MMS) were identified by the U.S. President as a major contributor to the Deepwater Horizon disaster in the Gulf of Mexico. The MMS has since been restructured into the Bureau of Ocean Energy Management, (BOEM) with separate departments responsible for drilling leases and the regulation of drilling activities. Similar restructuring of the oil and gas regulatory bodies in Canada is needed for better public information, scientific investigation and environmental protection in the offshore.

Blood group O and vWf expression may be involved in development of peptic ulcer disease secondary to Helicobacter pylori infection.

Helicobacter pylori is a gram negative organism involved in peptic ulcer disease and has been linked to a number of extra-intestinal diseases. There is a large body of evidence describing the link between blood group O/non-secretor phenotypes with H. pylori infection and the risk of peptic ulcer disease. Blood group O individuals also have a higher risk of bleeding disorders due to low levels of the circulating plasma protein von Willebrand factor (vWf). vWf is one of the main proteins that binds platelets during platelet activation and aggregation. The mechanisms of how ulcers develop during H. pylori infection are not fully understood. There is however recent evidence of vWf involvement in platelet aggregation in H. pylori infection. Our new hypothesis states that H. pylori bacteria present in blood group O/non-secretor individuals are binding the available vWf to promote adhesion and subsequent platelet aggregation within the microvasculature. This in turn may deplete any available vWf for wound repair to take place leading to an increased risk of peptic ulceration and bleeding and eventually leading to an ulcer.

Fluticasone induces T cell apoptosis in the bronchial wall of mild to moderate asthmatics.

BACKGROUND: Cytokines which signal via the gamma chain of the interleukin (IL)-2 receptor and the interferons (IFNs) have been shown to enhance T cell survival in vitro by rescuing cells from apoptosis. METHODS: A study was undertaken to determine whether treatment with inhaled fluticasone propionate (FP; 250 microg twice daily) for 2 weeks could modulate production of IL-15 or IFN-beta and thereby affect T cell survival in bronchial tissue of 10 patients with mild/moderate asthma. Bronchial biopsy specimens were taken before and on completion of treatment. RESULTS: The mean (95% CI) number of T cells per unit area decreased in the asthmatic group following 2 weeks of treatment with FP (from 7.0 (5.6 to 8.4) to 4.5 (4.0 to 5.1); p = 0.001). There was an increase in the percentage of T cells undergoing apoptosis following FP treatment as assessed by T cell/TUNEL staining (from 4.5 (2.6 to 6.4) to 8.7 (6.6 to 10.8); p = 0.0001). The percentage of cells staining for IL-15 and IFN-beta in the lamina propria, determined by an alkaline phosphatase biotin streptavidin technique, decreased significantly from baseline values of 31.6 (23.4 to 39.7) to 19.6 (12.5 to 26.7), p = 0.039 for IL-15 and from 18.9 (13.5 to 24.4) to 9.5 (5.9 to 13.1), p = 0.007 for IFN-beta following 2 weeks of treatment with FP. However, only the decrease in the percentage of cells staining for IL-15 was significantly correlated with an increased number of apoptotic T cells following treatment (p = 0.008). CONCLUSION: These findings support a novel mechanism for the ability of inhaled corticosteroids to decrease T cell numbers, possibly by downregulation of the cytokine IL-15.

Bed usage in a Dublin teaching hospital: a prospective audit.

AIMS AND METHODS: We prospectively audited inpatient bed use in our hospital for the first three months of this year. While 70% (mean age 54 +/- 20.8 years) of our patients went home on the day they were medically discharged, 30% (mean age 70.3 +/- 18.3 years) remained in the hospital awaiting step-down facilities. The total of 486 bed days occupied by overstaying patients would if available, have allowed treatment of 54% more patients without any increase in the hospital complement of beds, preventing the cancellation of elective procedures and preventing patients remaining on trolleys overnight. RESULTS AND CONCLUSION: These prospective data emphasise (1) a highly inefficient use of acute hospital beds; (2) the need for step-down facilities; (3) efficient use of existing hospital beds is the highest priority both for optimal patient care and optimal use of expensive hospital resources; (4) efficient use of existing facilities should be achieved before the construction of additional facilities.

Release of inflammatory mediators from eosinophils following a hyperosmolar stimulus.

Airway dehydration and subsequent hyperosmolarity of periciliary fluid are considered critical events in exercise-induced bronchoconstriction (EIB). It has been shown that an in vitro hyperosmolar stimulation of basophils and mast cells with mannitol can induce the release of histamine and leukotrienes. The aim of this study was to establish if a hyperosmolar challenge could trigger activation of eosinophils to release chemokines and lipid mediators. Peripheral blood eosinophils were isolated from seven asthmatic and six non-asthmatic subjects. Hyperosmolar stimulation of eosinophils with mannitol (0.7 M), resulted in a significant increase in LTC4 levels compared to baseline in both asthmatic (15.2+/-4.6 vs. 70.1+/-9.5; P = 0.0002) and control subjects (14.3+/-4.0 vs. 55.6+/-5.6; P = 0.0001). ECP levels did not increase significantly above baseline following mannitol stimulation in either group. This study shows that eosinophils can be activated by a hyperosmolar stimulus. Therefore it seems reasonable to suggest that eosinophils could contribute to EIB.

A case of frog breathing.

Frog breathing (glossopharyngeal breathing) is a useful technique employed to increase ventilation when respiratory muscles are paralysed. It is a technique used by many patients with chronic poliomyelitis, yet many chest physicians and physiotherapists are unfamiliar with this breathing maneuver. Glossopharyngeal breathing coordinates movements of the tongue, cheeks and pharynx to force air from the mouth into the lungs. We report a case of glossopharyngeal breathing, demonstrating a 3 fold increase in vital capacity in a subject with chronic poliomyelitis.

Immune responses of teleost fish.

In fish all the pre-requisites to mount a specific immune response are present, but the main differences from the mammalian system are that the secondary response is relatively minor and IgG is not present. In teleosts mainly IgM is present, and IgD has been recently described but its function is, as yet, unknown. However, different forms of fish IgM and its observed flexibility of structure may compensate for a lack of Ig class diversity. The innate immune response of teleosts is highly developed. Multiple forms of key constitutive and inducible components, such as lysozyme, C3, alpha2-macroglobulin and C-reactive protein, are present, and may enhance immune recognition. Low ambient temperature appears to have an impact on all aspects of the immune response, particularly the T-dependent specific immune response due to the non-adaptive lipid composition of T-cell membranes. Temperature effects on the nonspecific immune system are less well characterised, but there is evidence that low temperatures are also suppressive. Knowledge of immune system function becomes essential for disease prevention strategies such as the development of vaccines, selection for increased disease resistance and identification of genes suitable for trangenesis.

Rapid dendritic cell recruitment to the bronchial mucosa of patients with atopic asthma in response to local allergen challenge.

BACKGROUND: Airway dendritic cells (DC) play an important role in chronic allergic airway inflammation in experimental animals, but a similar role for DC in human allergic asthma has been difficult to define. This pilot study was undertaken to elucidate the role of DC in allergic asthma by examining their potential to migrate to the lower airways in response to bronchial challenge with specific allergen. METHODS: Bronchial biopsy specimens were obtained from seven patients with allergic asthma before and 4-5 hours after allergen challenge. Multicolour immunofluorescence staining was performed on mucosal cryosections to identify changes in the number and phenotypes of DC. RESULTS: A dramatic increase in the number of CD1c+HLA-DR+ DC were observed in the lamina propria after challenge compared with baseline (22.4 v 7.8 cells/mm(2)). The rapid accumulation (within 4-5 hours) of these cells strongly suggests that they were directly recruited from peripheral blood. CONCLUSION: We have shown for the first time that a specific DC subset rapidly emigrates into the human bronchial mucosa during allergic inflammation. While this study is based on relatively few patients, the consistency of the overall results strongly suggests that the rapid population dynamics of human airway DC closely parallel those in animal models of acute inflammation. These findings support suggestions that DC have an important role in human airway allergy.

Isolation and partial characterisation of immunoglobulin from southern bluefin tuna Thunnus maccoyii Castelnau.

Specific and total serum immunoglobulins were extracted by immunoaffinity, mannan-binding protein and Protein A affinity chromatography from southern bluefin tuna (Thunnus maccoyii Castelnau) immunised with rabbit IgG, and from non-immunised southern bluefin tuna. SDS-PAGE in 10% reducing gels revealed two heavy chains with molecular weights of approximately 74.6 +/- 1.3 kDa and 71.2 +/- 0.9 kDa, and two light chains with molecular weights of approximately 29 +/- 1.2 kDa and 28 +/- 1.0 kDa. Under non-reducing, but denaturing, conditions in 4% and 5% SDS-PAGE gels, a high molecular weight and a low molecular weight fraction were demonstrated. By gel filtration using Sephacryl HR 300 a molecular weight of 845 kDa, consistent with a tetramer, was obtained for the high molecular weight fraction, and a molecular weight of 168 kDa, consistent with a monomer, was obtained for the low molecular weight fraction. The extinction coefficient at A280 for the purified immunoglobulin (Ig) was determined to be 1.24. Tuna a-rabbit IgG Ig was reactive with all non-reduced mammalian IgG antigens tested, suggesting that common conformational antigenic determinants were recognised.

Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death.

This study investigates the presence of CD8(+) T lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. Postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease (control subjects). Using immunohistochemical techniques, the CD8(+) cytotoxic T-cell population in peribronchial tissue was characterized in three patient groups. The percentage of CD8(+) cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 +/- 1.92% versus 3.93 +/- 1.63% and 1.09 +/- 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 +/- 1.5%) compared with 1.39 +/- 0.9; 1.8 +/- 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN-gamma) by CD8(+) T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-gamma/IL-4 ratio in the AD group was less than half that of the control group (1.46 +/- 0.2 versus 3.2 +/- 0.1; p = 0.02). Using polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in lung tissue from three of the seven cases in the AD group. Two of these cases also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was detected in five of the AUC group and in one of these cases, RV was also detected. No viral genome was detected in the lungs of the control group. In conclusion, this study provides novel evidence of an aberrant CD8(+) T-cell population, possibly in response to viral infection in subjects who die of acute asthma.

IFN-gamma but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis.

BACKGROUND: Previous observations have established that IFN-gamma production is depressed in CD4+ T cells from atopic asthmatics compared with non-asthmatics. OBJECTIVE: The aim of this study was to determine if decreased IFN-gamma production could be due to a dissociation between levels of apoptosis within the T cell subsets of the asthmatic bronchial wall. METHODS: Twenty asthmatics (10 atopic and 10 non-atopic) and eight non-atopic non-asthmatics underwent bronchoscopy. Cryostat sections of these biopsies were investigated using immunohistological techniques to determine the relative number of CD4/FAS+ and CD4/Bcl-2+ cells. Detection of IFN-gamma+ and IL-4+ was combined with TUNEL staining to determine the proportions of the Th1 and Th2 cells undergoing apoptosis. RESULTS: Experiments revealed raised proportions of activated CD4+ T cells as assessed by expression of HLA-DR and CD25+ expression in the asthmatic samples. Expression of Bcl-2 by the CD4+ cell population was significantly reduced in the asthmatic compared with the control group (P = 0.002). There was no significant difference in the expression of CD4+ Fas-ligand or the number of CD4+ undergoing apoptosis in the asthmatic and non-asthmatic groups. However, the IFN-gamma+ (P = 0.04) but not IL-4+ T cells in the asthmatic biopsies had significantly higher proportions of apoptotic cells compared with the control group. CONCLUSION: The evidence supports the hypothesis that Th1/Th2 imbalance in asthmatic inflammation may be a result of premature apoptosis within the Th1 subset.

Macrophages : identification, separation, and function.

Within the human lung, macrophages can be found in the pleura, interstitium, alveoli, airways, vasculature, and walls of the bronchi and bronchiols. This distribution does not simply reflect the ubiquitous nature of these cells, as the macrophages found at these different sites show subtle distinctions in terms of cell physiology and phenotype (1). Further, animal studies have revealed functional differences between macrophages from different lung compartments (2). These differences may however be more apparent than real. Macrophages are motile cells and those, for example, present in the airways may arrive via the lung interstitium and are known to be capable of migrating back into the tissues of the lung. Thus, any observed differences between cells in different compartments are likely to be a reflection of the particular environment the cells find themselves in, rather than definitive distinctions between cell types (reviewed in 3). The message is that macrophages are "plastic" in terms of their phenotype. As different phenotypes have been shown to reflect different functions, it would seem inevitable, therefore, that these cells also exhibit a diversity of function. Indeed, it is now recognized that the phagocytic scavenger or microbicidal effector cell, are just two of several roles these cells can play.

Designing bronchial biopsy studies.

Bronchial biopsy provides valuable information about the inflammatory processes in lung tissue, but optimal results are only achieved if the design of intervention studies is sufficiently rigorous. The parallel-group design has merit, but the cross-over design is statistically superior, providing the wash-out period is effective. Heterogeneity of contributing pathologies in asthma patients results in large inter-patient variability which must be controlled for, for example by using strict inclusion criteria, which should ideally relate to the specific inflammatory marker being studied. The inclusion of a placebo group helps to quantify sample variability. The study must have sufficient statistical power to detect inter-group differences for each variable; appropriate adjustments should be made when multiple tests are used. Studies with larger patient numbers are best performed using a multi-centre design, with one centre analysing all tissue samples to reduce variability. Study duration depends on the type of investigation, but should ideally be short. Longer studies are necessary to evaluate chronic changes such as tissue remodelling. Changes in clinical status and cellular events may follow different time courses after intervention. Biopsy measurements are less reproducible than physiological tests, and diurnal variation in the number and function of inflammatory cells can further complicate measurement. The timing of clinical trial assessments needs to allow for these idiosyncrasies. Finally, a balance must be maintained between the risk, albeit small, and the benefit of performing bronchial biopsies.

The anti-inflammatory profile of inhaled corticosteroids: biopsy studies in asthmatic patients.

The beneficial effects of inhaled corticosteroids in the treatment of asthma are well established. A potent topical anti-inflammatory action is assumed to underlie the therapeutic effect, given that these agents alter the number and function of a range of inflammatory cells and markers in airway biopsies. This activity profile is shown by all inhaled corticosteroids, in a variety of patient types and study designs. Thus, treatment with inhaled corticosteroids leads to consistent reductions in the number and activation of mast cells and eosinophils in biopsy specimens. Other relevant findings include reductions in T-lymphocytes, which contribute to chronic inflammation via the secretion of pro-inflammatory cytokines (some of which are responsible for eosinophil accumulation and activation). Inhaled corticosteroids may therefore act by down-regulating immunoreactivity, so reducing activation of T lymphocytes and (consequently) eosinophils. There is considerable interest in whether corticosteroids can inhibit or reverse some structural changes in the airways, including basement membrane thickening, collagen deposition and increased airway vascularity; it has been suggested that these changes may contribute towards airway hyperresponsiveness and irreversible airway obstruction. In summary, inhaled corticosteroids have a broad spectrum of anti-inflammatory activity in asthma patients, but the relationship between changes in clinical and immunopathological parameters, particularly in the long-term, requires further study.