Antigen sensitization influences organophosphorus pesticide-induced airway hyperreactivity

BACKGROUND: Recent epidemiologic studies have identified organophosphorus pesticides (OPs) as environmental factors potentially contributing to the increase in asthma prevalence over the last 25 years. In support of this hypothesis, we have demonstrated that environmentally relevant concentrations of OPs induce airway hyperreactivity in guinea pigs. OBJECTIVES: Sensitization to allergen is a significant contributing factor in asthma, and we have shown that sensitization changes virus-induced airway hyperreactivity from an eosinophil-independent mechanism to one mediated by eosinophils. Here, we determine whether sensitization similarly influences OP-induced airway hyperreactivity. METHODS: Nonsensitized and ovalbumin-sensitized guinea pigs were injected subcutaneously with the OP parathion (0.001-1.0 mg/kg). Twenty-four hours later, animals were anesthetized and ventilated, and bronchoconstriction was measured in response to either vagal stimulation or intravenous acetylcholine. Inflammatory cells and acetylcholinesterase activity were assessed in tissues collected immediately after physiologic measurements. RESULTS: Ovalbumin sensitization decreased the threshold dose for parathion-induced airway hyperreactivity and exacerbated parathion effects on vagally induced bronchoconstriction. Pretreatment with antibody to interleukin (IL)-5 prevented parathion-induced hyperreactivity in sensitized but not in nonsensitized guinea pigs. Parathion did not increase the number of eosinophils in airways or the number of eosinophils associated with airway nerves nor did it alter eosinophil activation as assessed by major basic protein deposition. CONCLUSIONS: Antigen sensitization increases vulnerability to parathion-induced airway hyperreactivity and changes the mechanism to one that is dependent on IL-5. Because sensitization to allergens is characteristic of 50% of the general population and 80% of asthmatics (including children), these findings have significant implications for OP risk assessment, intervention, and treatment strategies.     

vanM,a New Glycopeptide Resistance Gene Cluster Found in Enterococcus faecium

Since glycopeptide-resistant enterococci (GRE) were reported in 1988, they have appeared in hospitals worldwide. Seven van gene cluster types (vanA, vanB, vanC, vanD, vanE, vanG, and vanL) are currently known. We investigated a clinical strain of Enterococcus faecium Efm-HS0661 that was isolated in 2006 from an inpatient with intra-abdominal infection in Shanghai. It was resistant to most antimicrobials, including vancomycin (MIC, >256 μg/ml) and teicoplanin (MIC, 96 μg/ml). Glycopeptide resistance could be transferred to E. faecium BM4105RF by conjugation. The donor and its transconjugant were negative by PCR for the known van genes. By cloning and primer walk sequencing, we discovered a novel van gene cluster, designated vanM. The vanM ligase gene was 1,032-bp in length and encoded a 343-amino-acid protein that shared 79.9, 70.8, 66.3, and 78.8% amino acid identity with VanA, VanB, VanD, and VanF, respectively. Although the vanM DNA sequence was closest to vanA, the organization of the vanM gene cluster was most similar to that of vanD. Upstream from the vanM cluster was an IS1216-like element, which may play a role in the dissemination of this resistance determinant. Liquid chromatography-mass spectrometry analysis of peptidoglycan precursors extracted from the VanM-type strain Efm-HS0661 treated with vancomycin or teicoplanin revealed a modified precursor (UDP-N-acetylmuramic acid [MurNAc]-tetrapeptide-d-Lac), indicating that VanM, like VanA, confers glycopeptide resistance by the inducible synthesis of precursor ending in d-Ala-d-Lac.Glycopeptide-resistant enterococci have emerged as important nosocomial pathogens since the late 1980s (18, 25). The glycopeptides vancomycin and teicoplanin act by binding to the d-alanyl-d-alanine (d-Ala-d-Ala) terminus of intermediates in peptidoglycan formation, inhibiting cell wall cross-linking (8). Resistance to glycopeptide antibiotics in enterococci results from the synthesis of peptidoglycan precursors with low affinity for these antibiotics, mediated by different van gene clusters (4, 8). Seven types of gene clusters conferring glycopeptide resistance have been described in enterococci based on DNA sequence and organization. They are designated according to the name of the ligase gene, which encodes either a d-Ala:d-Lac (vanA, vanB, and vanD) or a d-Ala:d-Ser (vanC, vanE, vanG, and vanL) ligase for the synthesis of peptidoglycan precursors with low affinity for glycopeptides. The vanA, vanB, and vanD gene clusters contain genes for a two-component regulatory system (vanR and vanS), three resistance genes (vanH, encoding dehydrogenase; vanA, vanB, or vanD, encoding ligase; vanX, encoding dd-dipeptidase); an accessory gene (vanY); and the vanZ gene, which is present in the vanA gene cluster, whereas the vanW gene is found only in the vanB operon (8). Another van gene cluster, vanF, has been described in a biopesticide, Paenibacillus popilliae (20), but has not yet been found in enterococci.Although vanA, vanB, and vanD gene clusters involve genes encoding similar enzymatic functions, they can be distinguished on the basis of the level and inducibility of resistance to glycopeptides and by the location of the genes (8, 11). The VanA type is characterized by acquired resistance to high levels of both vancomycin and teicoplanin, and it is induced by either vancomycin or teicoplanin. The VanB type is characterized by acquired resistance to various concentrations of vancomycin but not to teicoplanin and is induced only by vancomycin (1). VanA- and VanB-type resistances are the most common glycopeptide resistance phenotypes (23). The genes encoding the VanA and VanB phenotypes are carried on transposons, which may be found on plasmids or inserted into the chromosome (2).The VanD type is characterized by resistance to intermediate levels of vancomycin and to low levels of teicoplanin and is expressed constitutively (10, 12, 21). vanD genes appear to be located on the chromosome and are not transferable to other enterococci (12). This could explain the scarcity of recognized VanD strains in contrast to the widespread and high prevalence of VanA and VanB strains.Glycopeptide-resistant enterococci (GRE) were rare in China a few years ago (22), although vancomycin has been used in clinical practice for multidrug-resistant Gram-positive infections in mainland China for decades. In recent years, GRE strains isolated from hospitalized patients in mainland China have been increasing (6, 22, 27). In the course of determining the genotypes of glycopeptide-resistant Enterococcus faecium strains isolated from a teaching hospital in Shanghai, we found that several strains were negative by PCR for vanA, vanB, and vanD genes. The responsible glycopeptide resistance gene was cloned and sequenced from strain Efm-HS0661 and found to be novel. This new glycopeptide resistance gene cluster has been termed the vanM cluster. Of 10 unique GRE clinical strains isolated at our teaching hospital from 2005 to 2008, 6 carried vanM, which plays a role in the increasing GRE prevalence in China.     

The Role of Sensation in Subjective and Objective Evaluation of Nasal Patency

To assess if sensation of nasal mucosa affect the subjective sensation of nasal patency. This is a case control study with 50 patients, using 2% lignocaine as the active drug and normal saline as the placebo (2 groups of 25 patients each). Each subject had 2 ml of solution sprayed into the test nose. These subjects had no prior nasal symptoms, allergy or surgery. They were evaluated subjectively using Likert scale and objectively by acoustic rhinometry before and after lignocaine or normal saline. The patients in both normal saline and lignocaine groups demonstrated no significant change based upon Likert scale. The study also demonstrated the mean cross sectional area 1 (CSA1), mean cross sectional area 2 (CSA2), with mean Volume 1 and mean Volume 2, these results did not vary significantly in both groups with Acoustic Rhinometry. The analysis thus shows that the use of topical anesthetic spray on nasal mucosa produces no objective effect on nasal resistance or subjective sensation of altered nasal patency. Thus the study concludes that, tactile sensation of nasal mucosa does not play a role in the sensation of nasal obstruction.     

Sustained participation in annual continuous quality improvement activities improves quality of care for Aboriginal and Torres Strait Islander children

Aim

To determine whether participation in the continuous quality improvement (CQI) Audit and Best Practice for Chronic Disease programme improved care and outcomes for Indigenous children.

Methods

Data were collected from 59 Australian primary health‐care centres providing services to Indigenous people and participating in the programme (February 2008 and December 2013). Indigenous children aged less than 2 years and centres that completed three or more consecutive annual audits within the 6‐year study period were included. Crude and adjusted logistic generalised estimating equation models were used to examine the effect of year of audit on the delivery of care. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Outcomes were related to age‐relevant health issues, including prevention and early intervention. These included administrative, health check, anticipatory guidance and specific health issues.

Results

During the audit period, there were 2360 files from 59 centres. Those that had a recall recorded, improved from 84 to 95% (OR 2.44, 95% CI 1.44–4.11). Hearing assessments improved from 52 to 89% (OR 1.37, 95% CI 1.22–1.54). Improvement in anticipatory guidance, treatment and follow‐up of medical conditions was almost universal.

Conclusion

We documented significant improvements in quality of care of Indigenous children. Outcomes and their corresponding treatment and follow‐ups improved over time. This appears to be related to services participating in annual CQI activities. However, these services may be more committed to CQI than others and therefore possibly better performing.