Fiona Lake

House dust mite-derived amylase: Allergenicity and physicochemical characterization

Amylase activity was found in extracts of both Dermatophagoides pteronyssinus whole mite (0.16 U/mg) and spent growth medium (0.01 U/mg) but not in unused growth medium. It was also detected in all extracts of house dust obtained from mattresses (n = 20; geometric mean, 1.95 U/gm) and in 18 extracts of dust obtained from lounge room carpets (n = 20; geometric mean, 0.54 U/gm). Although the origins of amylase in dust are unclear, enzyme activity correlated with mite counts (n = 40; r = 0.35; p less than 0.05) and Der p I concentrations (r = 0.41; p less than 0.01). Mite amylase was purified from spent growth medium by affinity chromatography, gel filtration, and chromatofocusing. It was physicochemically similar to mammalian amylase with regard to molecular weight (60,000), charge heterogeneity (isoelectric point, 5 to 7) and the capacity to bind to an organomercurial affinity matrix. The optimum pH for enzymatic activity was revealed to be 6.4. IgE immunoblot studies demonstrated that the enzyme was allergenic and that its expression was dependent on the integrity of intrachain disulfide bonds. Sera from 25% of mite-allergic children and 46% of mite-allergic adults contained specific IgE to mite amylase. IgE to amylase was associated (p less than 0.01) with increased concentrations of total mite-specific IgE determined with a direct RAST assay.

Faecally derived hydrolytic enzymes from Dermatophagoides pteronyssinus : physicochemical characterisation of potential allergens

The previous findings that the group I and III mite allergens, and amylase present in mite faeces are hydrolytic enzymes has prompted a study to determine whether this material contains other enzymes which could be allergenic. Thus, spent growth medium devoid of whole Dermatophagoides pteronyssinus mites was shown to contain glucoamylase, lipase and lysozyme in addition to the cysteine protease, serine protease and amylase activities associated with the above allergens, respectively. All of these enzymes are probably associated with mite digestive processes. They were rapidly solubilised, heterogeneous with regard to charge (pI in the range 4-8) and demonstrated maximum biochemical activity in the neutral pH range. Three serine proteases were detected and comprised a chymotrypsin-like, a trypsin-like and an unclassified enzyme with pI of 4.1 and 5.3, 8.5 and 7.1, respectively. Only one cysteine protease was observed, which paralleled immunochemically identified Der p I in a variety of assays. It was shown to cleave at lysyl residues and could be inhibited by the specific cysteine protease inhibitor, E-64. The remaining serine proteases, glucoamylase, lipase and lysozyme represent potential allergens.

A new unsupported upper limb exercise test for patients with chronic obstructive pulmonary disease

UNLABELLED PURPOSE This study aimed to develop a new unsupported upper limb exercise test (UULEX) for patients with chronic obstructive pulmonary disease (COPD). METHODS The reproducibility of the UULEX was assessed in nine patients with COPD who performed the test on three occasions. A comparison of the UULEX and a supported incremental upper limb exercise test (SULEX) using an arm ergometer also was performed with 18 patients who had COPD. RESULTS There were no significant differences in the maximum values for each cardiorespiratory variable and sensation of dyspnea between the three repetitions of the UULEX, and all the variables showed high reproducibility. During the supported test, maximum values for the cardiorespiratory variables were significantly higher, but the ratio of minute ventilation to carbon dioxide output was lower than during the unsupported exercise test. There were significant correlations for cardiorespiratory responses, arm muscle fatigue, and sensation of dyspnea between the two tests. CONCLUSIONS The findings suggest that the new UULEX test is a reproducible and acceptable exercise test for patients with COPD that can be used as a simple method to evaluate upper limb function in these patients. Further studies are required to determine the external validity of the test and its sensitivity to interventions such as pulmonary rehabilitation.

Peer-assisted learning in teaching clinical examination to junior medical students

Background: In medical education, peer-assisted learning (PAL) refers to teaching occurring between fellow students. Few descriptions of its use to teach clinical examination have been published. Student Grand Rounds (SGR) is a student-led initiative whereby senior students volunteer to teach clinical examination to pre-clinical peers. Student tutors attend a modified Teaching on the Run (TOTR) course originally designed to train clinicians to teach students and junior doctors. Aim: We investigated the value of SGR in teaching pre-clinical students, and evaluated the effectiveness of TOTR. Methods: Over 9 months, tutors and participants in each SGR tutorial completed an online survey. At the conclusion of annual TOTR workshops (2004–2010), participants evaluated their impressions of the course. Results: A total of 64 SGR tutorials were attended by a total of 321 students. All agreed that tutorials were beneficial and enjoyable, with a threefold increase in the number of students self-identifying as able to perform the skills required. TOTR participants classified the course as both relevant and beneficial, and all course outcomes were achieved. SGR tutors reported improved knowledge and confidence in teaching following SGR and TOTR. Conclusion: PAL is effective in supplementing teaching of clinical examination. Senior students learn valuable skills and gain experience in teaching.

Short- and long-term hospital and community exercise programmes for patients with chronic obstructive pulmonary disease

Objective:  Pulmonary rehabilitation in patients with COPD has been shown to be beneficial but the optimal setting is not known. In the present study, the efficacy of a short‐term community‐based exercise programme was compared with a standard hospital outpatient programme. Additionally, the usefulness of community or home programmes in maintaining improvements in the longer term was studied.

Five-year outcome in COPD patients after their first episode of acute exacerbation treated with non-invasive ventilation

Background and objective:  Little is known about long‐term survival of patients surviving the first episode of type II respiratory failure requiring non‐invasive ventilation (NIV). We aimed to determine the 1‐, 2‐ and 5‐year survival, cause of death and potential prognostic indicators in this patient cohort.

Rheumatoid arthritis and lung disease: From mechanisms to a practical approach

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease characterized by joint inflammation and, in a proportion of patients, extra-articular manifestations (EAM). Lung disease, either as an EAM of the disease, related to the drug therapy for RA, or related to comorbid conditions, is the second commonest cause of mortality. All areas of the lung including the pleura, airways, parenchyma, and vasculature may be involved, with interstitial and pleural disease and infection being the most common problems. High-resolution computed tomography of the chest forms the basis of investigation and when combined with clinical information and measures of physiology, a multidisciplinary team can frequently establish the diagnosis without the need for an invasive biopsy procedure. The most frequent patterns of interstitial lung disease (ILD) are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), with some evidence for the prognosis being better than for the idiopathic equivalents. Risk factors depend on the type of disease but for ILD (mainly UIP and NSIP) include smoking, male gender, human leukocyte antigen haplotype, rheumatoid factor, and anticitrullinated protein antibodies (ACPAs). Citrullination of proteins in the lung, frequently thought to be incited by smoking, and the subsequent development of ACPA appear to play an important role in the development of lung and possibly joint disease. The biologic and nonbiological disease modifying antirheumatic drugs (DMARDs) have had a substantial impact on morbidity and mortality from RA, and although there multiple reports of drug-related lung toxicity and possible exacerbation of underlying ILD, overall these reactions are rare and should only preclude the use of DMARDs in a minority of patients. Common scenarios facing pulmonologists and rheumatologists are addressed using the current best evidence; these include screening the new patient; monitoring and choosing RA treatment in the presence of subclinical disease; treating deteriorating ILD; and establishing a diagnosis in a patient with an acute respiratory presentation.

Clinical teaching and learning: from theory and research to application

Learning in the clinical setting is the cornerstone of medical school education, but there are strong imperatives to optimise the ways in which students acquire clinical expertise. Deliberate practice is characterised by attention, concentration, effort and repetition of skills; it is an important tool for developing and maintaining professional expertise. Research has led to a greater understanding of how medical students develop core clinical skills, especially in the areas of diagnostic reasoning, communication and physical examination. Advances in information technology and instructional design are helping to strengthen the links between formal educational activities and opportunistic learning in the clinical setting.

Allergenicity and physicochemical characterization of house dust mite derived amylase.

The enzyme amylase was shown to be present in extracts prepared from both house dust and spent growth medium used in the culture of the mite Dermatophagoides pteronyssinus. In dust, it was shown to correlate with both mite counts and concentrations of the faecally derived mite allergen, Der p I. Mite amylase was isolated from the culture medium and shown to be a single chain protein with a molecular weight of 56,000. The enzyme contained free sulphydryl groups and had the N-terminal sequence, KYXNPHFIGXRSVITXLME. It was found to be an allergen using sera from adults (46% positive) and children (25%) who were mite allergic. The expression of allergenicity was dependent on the integrity of intra-chain disulphide bonds.

Relationships between academic performance of medical students and their workplace performance as junior doctors

BackgroundLittle recent published evidence explores the relationship between academic performance in medical school and performance as a junior doctor. Although many forms of assessment are used to demonstrate a medical student’s knowledge or competence, these measures may not reliably predict performance in clinical practice following graduation.MethodsThis descriptive cohort study explores the relationship between academic performance of medical students and workplace performance as junior doctors, including the influence of age, gender, ethnicity, clinical attachment, assessment type and summary score measures (grade point average) on performance in the workplace as measured by the Junior Doctor Assessment Tool.ResultsThere were two hundred participants. There were significant correlations between performance as a Junior Doctor (combined overall score) and the grade point average (r = 0.229, P = 0.002), the score from the Year 6 Emergency Medicine attachment (r = 0.361, P < 0.001) and the Written Examination in Year 6 (r = 0.178, P = 0.014). There was no significant effect of any individual method of assessment in medical school, gender or ethnicity on the overall combined score of performance of the junior doctor.ConclusionPerformance on integrated assessments from medical school is correlated to performance as a practicing physician as measured by the Junior Doctor Assessment Tool. These findings support the value of combining undergraduate assessment scores to assess competence and predict future performance.