Surgical management of large bowel obstruction and significant hepatic displacement caused by Chilaiditi syndrome.

Chilaiditi's sign is the presence of pseudopneumoperitoneum caused by colonic distension and interposition with the liver on radiographic films. Most patients with Chilaiditi's sign are asymptomatic. Chilaiditi's syndrome is defined as the development of abdominal pain or symptoms of bowel obstruction along with the presence of Chilaiditi's sign. It is a rare entity and it poses significant diagnostic challenges due to its similar radiographic appearance to pneumoperitoneum. Most patients with Chilaiditi syndrome can be managed conservatively. However, surgery is indicated for those who do not respond to conservative management or for suspicion of severe complications such as bowel ischaemia or perforation. In this case report, we described the surgical management of a patient who presented with bowel obstruction and significant hepatic displacement from Chilaiditi syndrome.

Combined Haemophilus influenzae respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma.

BACKGROUND: 20-30% of patients with asthma have neutrophilic airway inflammation and reduced responsiveness to steroid therapy. They often have chronic airway bacterial colonisation and Haemophilus influenzae is one of the most commonly isolated bacteria. The relationship between chronic airway colonisation and the development of steroid-resistant neutrophilic asthma is unclear. OBJECTIVES: To investigate the relationship between H influenzae respiratory infection and neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced allergic airways disease. METHODS: BALB/c mice were intratracheally infected with H influenzae (day 10), intraperitoneally sensitised (day 0) and intranasally challenged (day 12-15) with OVA. Treatment groups were administered dexamethasone intranasally during OVA challenge. Infection, allergic airways disease, steroid sensitivity and immune responses were assessed (days 11, 16 and 21). RESULTS: The combination of H influenzae infection and allergic airways disease resulted in chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31 days after infection). Neutrophilic allergic airways disease and T helper 17 cell development were induced, which did not require active infection. Importantly, all features of neutrophilic allergic airways disease were steroid resistant. Toll-like receptor 4 expression and activation of phagocytes was reduced, but most significantly the influx and/or development of phagocytosing neutrophils and macrophages into the airways was inhibited. CONCLUSIONS: The combination of infection and allergic airways disease promotes bacterial persistence, leading to the development of a phenotype similar to steroid-resistant neutrophilic asthma and which may result from dysfunction in innate immune cells. This indicates that targeting bacterial infection in steroid-resistant asthma may have therapeutic benefit.

Haemophilus influenzae infection drives IL-17-mediated neutrophilic allergic airways disease.

A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark features of asthma in a mouse model of allergic airways disease (AAD). BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and intranasally challenged with OVA 12-15 days later to induce AAD. Mice were infected with non-typeable H. influenzae during or 10 days after sensitization, and the effects of infection on the development of key features of AAD were assessed on day 16. T-helper 17 cells were enumerated by fluorescent-activated cell sorting and depleted with anti-IL-17 neutralizing antibody. We show that infection in AAD significantly reduced eosinophilic inflammation, OVA-induced IL-5, IL-13 and IFN-γ responses and AHR; however, infection increased airway neutrophil influx in response to OVA challenge. Augmented neutrophilic inflammation correlated with increased IL-17 responses and IL-17 expressing macrophages and neutrophils (early, innate) and T lymphocytes (late, adaptive) in the lung. Significantly, depletion of IL-17 completely abrogated infection-induced neutrophilic inflammation during AAD. In conclusion, H. influenzae infection synergizes with AAD to induce Th17 immune responses that drive the development of neutrophilic and suppress eosinophilic inflammation during AAD. This results in a phenotype that is similar to neutrophilic asthma. Infection-induced neutrophilic inflammation in AAD is mediated by IL-17 responses.

Acute exacerbations in COPD and their control with oral immunization with non-typeable haemophilus influenzae.

Chronic obstructive pulmonary disease (COPD) a term based on the demonstration of irreversible airways obstruction, introduced to unify a range of chronic progressive diseases of the airways consequent upon inhalation of toxins. While disease is initiated and progressed by inhaled toxins, an additional pathway of damage has emerged, with particular relevance to acute exacerbations. Exacerbations of disease due to an increase in the level of intrabronchial inflammation have taken on a new significance as their role in determining both acute and chronic outcomes is better understood. This "second pathway" of disease is a consequence of bacterial colonization of damaged airways. Although bacteria have been linked to acute episodes in COPD over 50 years, only recently has quality data on antibiotic usage and the detection of "exacerbation isolates" of non-typeable Haemophilus influenzae (NTHi) provided strong argument in support of a pathogenic role. Yet a poor correlation between detection of colonizing bacteria and clinical status remained a concern in attempts to explain a role for bacteria in a classical infection model. This presentation discusses a hypothesis that acute exacerbations reflect a T cell-dependent hypersensitivity response to colonizing bacteria, with IL-17 dependent accumulation of neutrophils within the bronchus, as the main outcome measure. Critical protection against exacerbations following oral administration of NTHi, an immunotherapy that drives a TH17 T cell response from Peyer's patches, reduces the load of intrabronchial bacteria while preventing access of inhaled bacteria into small airways. Immunotherapy augments a physiological "loop" based on aspiration of bronchus content into the gut. A second "hypersensitivity" mechanism may cause bronchospasm - in both COPD and treatment-resistant asthma - due to specific IgE antibody directed against colonizing bacteria, as oral NTHi abrogates wheeze in subjects with recurrent "wheezy bronchitis."

Oral immunotherapy with inactivated nontypeable Haemophilus influenzae reduces severity of acute exacerbations in severe COPD.

BACKGROUND: Acute exacerbations of COPD reflect in part an inappropriate host response to abnormal bacterial colonization. Orally administered inactivated nontypeable Haemophilus influenzae (NTHi) can drive a specific T-cell response that by promoting intrabronchial phagocytosis down-regulates bronchus inflammation. METHODS: Subjects with recurrent exacerbations of COPD were studied in a randomized, multicenter, double-blind, placebo-controlled trial, to test efficacy of an NTHi oral immunotherapeutic (HI-164OV). This report describes the outcome in 38 subjects with severe COPD defined as having an FEV(1) < or = 50% of predicted normal. RESULTS: Exacerbations defined as an increase in volume and purulence of sputum were reduced by 16% (not significant) in the active group. However, moderate-to-severe exacerbations (defined as requiring corticosteroid therapy) were reduced by 63% (P = .05). The proportion with any acute exacerbation was little changed with treatment, but the proportion with episodes requiring corticosteroid therapy was reduced by 56% (P = .07). The mean duration of episodes was reduced by 37% (P = .01) and prescribed courses of antibiotics were reduced by 56% (P = .03) following therapy. Exacerbations requiring admission into hospital were reduced by 90% (P = .04) in the active group. No specific adverse effect was detected. CONCLUSIONS: Treatment of severe COPD with frequent exacerbations with HI-164OV was safe and effective, especially with respect to reduction in parameters of severity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au; identifier: ACTRN012606000074594.

Mucosal immunology down under: Special Interest Group in Mucosal Immunology workshop, Australasian Society for Immunology, Sydney, Australia, 2 December 2007.

The Mucosal Immunology Special Interest Group (SIG-MI) of the Australasian Society of Immunology was formed 14 years ago and has run regular symposia and workshops in conjunction with the Australasian Society of Immunology since that time. In December 2007 the Mucosal Immunology Special Interest Group held a 1-day satellite workshop in conjunction with the annual Australasian Society of Immunology scientific meeting in Sydney to celebrate the decade since hosting the 9th International Congress of Mucosal Immunology (9-ICMI) in 1997, which was also held in Sydney. The meeting that was attended by 65 delegates focussed on 4 session themes: reproductive immunology, respiratory immunology, mucosal immunology of the gastrointestinal tract and mucosal vaccines.

"Not-for-resuscitation" orders in Australian public hospitals: policies, standardised order forms and patient information leaflets.

OBJECTIVE: To determine the prevalence and content of policies, standardised order forms (SOFs) and patient information leaflets (PILs) pertaining to "not-for-resuscitation" (NFR) orders in Australian public hospitals. DESIGN AND SETTING: Cross-sectional postal survey conducted across Australia from August to December 2005, using a one-page questionnaire. PARTICIPANTS: Directors of Medical, Nursing or Clinical Services of all public hospitals in Australia with 60 or more beds, excluding psychiatric, military and private hospitals. MAIN OUTCOME MEASURES: Prevalence of documented NFR policies, by hospital characteristics, and content of these policies, SOFs and PILs. RESULTS: 222 hospitals were surveyed, and 157 responded (71%). Of these, 85 (54%) had NFR policies, 62 (39%) had SOFs, and four (3%) had PILs. Hospitals with more than 200 beds were more likely to have NFR policies than those with 60-200 beds (P = 0.04). More metropolitan than rural hospitals had NFR policies (P = 0.01). More hospitals with 60-100 beds had SOFs than hospitals with 101-200 beds (P = 0.03). "NFR" was defined in 53% of policies, while 97% of policies explicitly stated where NFR orders were to be documented, 89% stated who was allowed to make them, 37% stated that advanced care directives ("living wills") were to be respected, and 89% stated that competent patients should be involved in discussions regarding their NFR status. The most common items noted in SOFs were the name and signature of the issuing medical practitioner (92%) and documentation of the discussion with the patient (81%). CONCLUSIONS: There was wide variation in the content of hospital policies, SOFs and PILs pertaining to NFR orders. Aspects of current policies show room for improvement.

Response of IgG1 and IgG2 subclasses to Helicobacter pylori in subjects with chronic inflammation of the gastric mucosa, atrophy and gastric cancer in a country with high Helicobacter pylori infection prevalence.

Polarized immune response to Helicobacter pylori and induction of chronic inflammation may increase the risk of gastric atrophy and adenocarcinoma. We studied the association of the response of IgG1 and IgG2 antibodies to H. pylori with grade of gastric chronic inflammation and atrophy in a population with a high prevalence of H. pylori, and compared these data with the data obtained from the study of gastric cancer patients, as well as with the data for CagA positivity. Altogether, 114 persons from two adult population samples from Estonia and 45 consecutive gastric cancer patients were studied. All patients were positive for the H. pylori antibody determined by ELISA. Adenocarcinoma was classified histologically according to the Laurén's system. The response of the IgG subclasses to H. pylori (acid glycine-extracted whole cell proteins) was determined by ELISA and the results were compared with the ELISA results for the recombinant fragment of the CagA protein. Helicobacter pylori IgG level was lower in atrophic gastritis compared with nonatrophic gastritis (chronic inflammation) (p=0.001). In the group of cancer patients, the response of IgG and IgG1 was lower compared with both gastritis groups (p=0.01 and p=0.0002 for IgG, and p=0.001 and p=0.0005 for IgG1). IgG2 was lower for gastric cancer localized in the corpus (p=0.03). In conclusion, atrophic gastritis and gastric cancer were associated with a significant decline in IgG and IgG1 response to H. pylori compared with nonatrophic gastritis. Higher value of CagA antibodies was seen in gastric cancer and in gastric atrophy compared with nonatrophic gastritis; in gastric cancer patients, IgG1 response to H. pylori was correlated with CagA status.

Safety and immunogenicity of an oral inactivated whole-cell pseudomonas aeruginosa vaccine administered to healthy human subjects.

This study examines the safety and immunogenicity of an oral, whole-cell Pseudomonas aeruginosa vaccine administered to healthy volunteers. Thirty subjects received an oral dose of Pseudostat in two timed, measured doses with serological follow-up to 56 days postvaccination. Following vaccination, several individuals were identified as antibody responders for all three immunoglobulin (Ig) isotypes tested, specifically against whole-cell P. aeruginosa extract and outer membrane proteins F and I. The mean pooled lipopolysaccharide antigen-specific IgA showed the most significant and constant increases in titer postdose, with a similar increase in titer for whole-cell P. aeruginosa extract-specific IgA. The results demonstrated an increased phagocytic ability of the selected macrophage cell line in post vaccination sera. Furthermore a significant increase in intracellular macrophage killing of opsonized P. aeruginosa was also demonstrated (82% on day 14 postdose) in the presence of the postvaccination sera. The safety component of the study did not show any vaccine-attributable adverse effects in any of the subjects, as documented by clinical evidence, hematology, and biochemistry profiles. We conclude that Pseudostat is safe and immunogenic in humans at this dose and that further studies to determine the appropriate dosage and efficacy are needed. In our study, we have shown that the most significant and sustained responses to oral vaccination in human adult volunteers were serum IgA levels and that pooled sera collected postimmunization have an increased capacity to promote opsonophagocytotic killing of P. aeruginosa.

Selective reduction of anti-Helicobacter pylori IgG subclass antibody in gastric carcinoma.

BACKGROUND: Epidemiological studies have demonstrated strong links between Helicobacter pylori infection and gastric adenocarcinoma. Recent studies suggest that cell-mediated immunity influences the outcome of infection, including the development of gastric adenocarcinoma. The T-cell response can be characterized in terms of the secreted cytokine profile, which in turn influences the B-cell response including the balance of IgG subclass antibody. METHODS: Serum anti-H. pylori IgG, IgG1 and IgG2 antibodies were studied by ELISA in subjects with benign gastric diseases, gastric dysplasia and gastric adenocarcinoma. RESULTS: The distribution patterns of IgG subclass anti-H. pylori antibody varies significantly between H. pylori-linked benign and malignant disease in subjects infected with H. pylori. Significantly lower IgG2 levels were found in subjects with gastric adenocarcinoma compared with those with reflux esophagitis, chronic gastritis, gastric ulcer, and peptic ulcer, while IgG1 antibody remained at similar levels in both benign and malignant disease. A limited study of seropositive subjects with premalignant change was consistent with the fall in IgG2 antibody pre-dating malignant change, although pre-eradication results are needed to validate these data. CONCLUSIONS: These studies indicate that subjects with low levels of IgG2 anti-H. pylori antibody are at risk of gastric adenocarcinoma, and that the previously described linkage between gastric adenocarcinoma and low total IgG antibody does not simply reflect reduced gastric colonization. The diagnostic value of this assay for pre-endoscopy screening is attractive.

Pseudomonas aeruginosa-specific IgG1 and IgG2 subclasses in enhancement of pulmonary clearance following passive immunisation in the rat.

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen, which causes serious debilitating infections in patients with compromised lung function. The mechanism by which P. aeruginosa is cleared from the lung is not fully defined, although our previous studies have established a role for cellular immunity in protection against P. aeruginosa infections. This study aimed to evaluate the role of P. aeruginosa-specific IgG in protection against P. aeruginosa in a rat model of acute pulmonary infection. Immunoaffinity chromatography was used to purify total rat IgG from rat immune serum (rats immunised with P. aeruginosa) and non-immune serum. Untreated recipient rats were injected intravenously with different concentrations of pure IgG prepared from serum of unimmunised rats (non-immune IgG) or from rats immunised intestinally with killed P. aeruginosa (immune IgG) and infected intratracheally with P. aeruginosa 18 h later. The protective capability of the purified IgG against P. aeruginosa was assessed by measurement of reduction in P. aeruginosa infection in the lung 4 h after instillation of bacteria. Enhanced bacterial clearance induced by IgG was determined to be dose-dependent with a 1 mg dose failing to enhance clearance, whereas 5 mg of immune IgG enhanced clearance from the airways and the lung tissue. Measurement of the IgG1, IgG2a and IgG2b isotypes in serum and the lung lavage following transfer of P. aeruginosa-specific IgG found that all three were present. These results demonstrate that anti-P. aeruginosa IgG can enhance bacterial clearance from the airways in an acute infection and identify an important role for IgG in acute respiratory infections caused by P. aeruginosa.

Immunisation with non-integral OMPs promotes pulmonary clearance of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that can cause fatal acute lung infections in critically ill individuals. Lung damage due to chronic infections in cystic fibrosis sufferers is the major cause of morbidity and mortality in this group. The bacterium produces various immunomodulatory products that enable it to survive in the lung. Innate and increasing resistance to antibiotic therapy shown by this organism heightens the need for development of a vaccine. This study reports the identification of six non-integral protein antigens; Pa13, azurin, acyl carrier protein (ACP), amidase, aminopeptidase and KatE, purified from a mucoid strain of P. aeruginosa. N-terminal amino acid sequencing was used to identify these proteins and, based on their ascribed functions, determined that their normal cellular location was cytosolic. A rat model of acute pulmonary infection was used to investigate the ability of these protein antigens to enhance pulmonary clearance of a live P. aeruginosa challenge. Mucosal immunisation with four of the six antigens significantly enhanced bacterial clearance from both the lavage fluid and lung tissue. The greatest level of clearance was demonstrated for the antigens; KatE, aminopeptidase and amidase. Enhanced bacterial clearance was maintained when the antigens amidase and aminopeptidase were produced in recombinant form. When delivered parenterally, aminopeptidase demonstrated its continued efficacy as a vaccine candidate. This study has demonstrated that non-integral outer membrane proteins are antigenic and protective and warrant further investigation as potential components of a vaccine.