Can peak expiratory flow measurements reliably identify the presence of airway obstruction and bronchodilator response as assessed by FEV1 in primary care patients presenting with a persistent cough?

BACKGROUND: In general practice airway obstruction and the bronchodilator response are usually assessed using peak expiratory flow (PEF) measurements. A study was carried out in patients presenting with persistent cough to investigate to what extent PEF measurements are reliable when compared with tests using forced expiratory volume in one second (FEV(1)) as the measure of response. METHODS: Data (questionnaire, physical examination, spirometry, PEF) were collected from 240 patients aged 18-75 years, not previously diagnosed with asthma or chronic obstructive pulmonary disease (COPD), who consulted their general practitioner with cough of at least two weeks duration. The relationship between low PEF (PEF < PEFpred - 1.64RSD) and low FEV(1) (FEV(1) < FEV(1)pred - 1.64RSD) was tested. A positive bronchodilator response after inhaling 400 microg salbutamol was defined as an increase in FEV(1) of > or = 9% predicted and was compared with an absolute increase in PEF with cut off values of 40, 60, and 80 l/min and DeltaPEF % baseline with cut off values of 10%, 15%, and 20%. RESULTS: Forty eight patients (20%) had low FEV(1), 86 (35.8%) had low PEF, and 32 (13.3%) had a positive bronchodilator response. Low PEF had a positive predictive value (PPV) for low FEV(1) of 46.5% and a negative predictive value (NPV) of 95%. DeltaPEF of > or = 10%, > or = 15%, or > or = 20% baseline had PPVs of 36%, 52%, and 67%, respectively, and DeltaPEF of > or = 40, > or = 60, and > or = 80 l/min in absolute terms had PPVs of 39%, 45%, and 57%, respectively, for DeltaFEV(1) > or = 9% predicted; NPVs were high (88-93%). CONCLUSIONS: Although PEF measurements can reliably exclude airway obstruction and bronchodilator response, they are not suitable for use in the assessment of the bronchodilator response in the diagnostic work up of primary care patients with persistent cough. The clinical value of PEF measurements in the diagnosis of reversible obstructive airway disease should therefore be re-evaluated.     

Enhanced crystallization by annealing of poly(phenylene sulfide) in presence of CO2 and N2O

Crystallization of amorphous poly(phenylene sulfide) was carried out upon annealing in the presence of sorbed CO₂ and N₂O at pressures of 50 bar. Thermal crystallization at the same pressure allows the comparison of crystallization rates. From the results of IR-spectroscopy, wide angle X-ray diffraction, differential scanning calorimetry and density measurements, it is seen that in the presence of sorbed gas molecules crystallization occurs even at temperatures below the glass transition measured at atmospheric conditions. At a given temperature, gas sorption yields accelerated crystallization. The results, show the considerable plasticizing influence of sorbed gas molecules. From the crystallization rate at sorbed gas conditions the plasticizing ability of the gas may be estimated. That of N₂O exceeds that of CO₂ by a factor of three. Assuming a simple two-phase model for the crystalline polymer the comparison of heat of melting and density values for t → ∞ allows the conclusion that parts of the noncrystalline volume fraction become less dense by annealing in the presence of sorbed gas molecules. An increased free volume fraction which may be formed in the non-crystalline regions is discussed. It is possible that the remaining lower density results from a hindered relaxation of chain molecules from the dilated state they take due to gas sorption. In this context the influence of decreased mobility of non-crystalline chains is discussed in terms of the “rigid amorphous phase” concept.     

Culture of cells gained from temporomandibular joint cartilage on non-absorbable scaffolds

The objective of this study was to investigate the adhesion, spreading and extracellular matrix synthesis of temporomandibular joint (TMJ) derived cells on non-absorbable scaffold materials to ultimately provide a durable stress-absorbent framework within tissue-engineered disc transplants. Scaffolds were prepared by polyamide monofilaments, expanded polytetrafluoroethylene (ePTFE) monofilaments, polyglycolic acid monofilaments (control) or natural bone mineral blocks (control). These scaffolds were incubated for 2, 4 and 8 weeks under common culture conditions with cells (human and porcine) harvested from the TMJ-disc or the articular eminence. The specimens were examined by scanning electron microscopy and transmission electron microscopy. The type of collagen synthesized was analyzed by SDS-PAGE. The cells were strongly adherent to all of the materials. Independent of their origin the cells became confluent on all scaffolds within four weeks. They filled recesses loosely and covered the constructs by an envelope of dense stratified cell layers. Moreover, the cells expressed collagen type II, which is specific for chondrocytes. Thus, it could be demonstrated, that ePTFE, polyamide, polyglycolic acid and natural bone mineral have an excellent compatibility in a three-dimensional cell culture system. ePTFE and polyamide scaffolds may be well suited for the development of tissue-engineered stress-resistant articular disc transplants.     

Two-laboratory collaborative study on identification of mycobacteria: molecular versus phenotypic methods.

Previous studies have indicated that the conventional tests used for the identification of mycobacteria may (i) frequently result in erroneous identification and (ii) underestimate the diversity within the genus Mycobacterium. To address this issue in a more systematic fashion, a study comparing phenotypic and molecular methods for the identification of mycobacteria was initiated. Focus was given to isolates which were difficult to identify to species level and which yielded inconclusive results by conventional tests performed under day-to-day routine laboratory conditions. Traditional methods included growth rate, colonial morphology, pigmentation, biochemical profiles, and gas-liquid chromatography of short-chain fatty acids. Molecular identification was done by PCR-mediated partial sequence analysis of the gene encoding the 16S rRNA. A total of 34 isolates was included in this study; 13 of the isolates corresponded to established species, and 21 isolates corresponded to previously uncharacterized taxa. For five isolates, phenotypic and molecular analyses gave identical results. For five isolates, minor discrepancies were present; four isolates remained unidentified after biochemical testing. For 20 isolates, major discrepancies between traditional and molecular typing methods were observed. Retrospective analysis of the data revealed that the discrepant results were without exception due to erroneous biochemical test results or interpretations. In particular, phenotypic identification schemes were compromised with regard to the recognition of previously undescribed taxa. We conclude that molecular typing by 16S rRNA sequence determination is not only more rapid (12 to 36 h versus 4 to 8 weeks) but also more accurate than traditional typing.     

Heterogenous glycosylation of ICAM-3 and lack of interaction with Mac-1 and p150,95

Intercellular adhesion molecule (ICAM)-1, ICAM-2, and ICAM-3 have been identified as counter-receptors for the leukocyte integrin lymphocyte function-associated antigen 1 (LFA-1). The other leukocyte integrins, Mac-1 and p150,95, also interact with ICAM-1. ICAM-1 and ICAM-3 are highly homologous, and an undefined ligand for Mac-1 is presnt on neutrophils where ICAM-3 is well expressed. In addition, glycosylation has been shown to affect the interaction of ICAM-1 with Mac-1. We therefore sought to characterize ICAM-3 heterogeneity and determine whether ICAM-3 was a ligand for either Mac-1 or p150,95. Despite extensive differences in N-linked glycosylation, ICAM-3 purified from lymphoid cells and from neutrophils supports adhesion of LFA-1-bearing cells equally well; however, neither supports adhesion of Mac-1 or p150,95-expressing chinese hamster ovary cell transfectants. Similarly, purified Mac-1 does not support adhesion of ICAM-2 or ICAM-3-expressing L cell transfectants. ICAM-3 on neutrophils does not participate in Mac-1-dependent homotypic aggregation. Thus, ICAM-3 is not a counter-receptor for either Mac-1 or p150,95.     

Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells

Eotaxin is a newly discovered C-C chemokine which preferentially attracts and activates eosinophil leukocytes by acting specifically on its receptor CCR3. The airway inflammation characteristic of asthma is believed to be, at least in part, the result of eosinophil-dependent tissue injury. This study was designed to determine whether there is increased expression of eotaxin and CCR3 in the bronchial mucosa of asthmatics and whether this is associated with disease severity. The major sources of eotaxin and CCR3 mRNA were determined by co-localization experiments. Bronchial mucosal biopsy samples were obtained from atopic asthmatics and normal non-atopic controls. Eotaxin and CCR3 mRNA were identified in tissue sections by in situ hybridization (ISH) using radiolabeled riboprobes and their protein product visualized by immunohistochemistry (IHC). Co-localization experiments were performed by double ISH/IHC. Eotaxin and CCR3 (mRNA and protein) were significantly elevated in atopic asthmatics compared with normal controls. In the asthmatics there was a highly significant inverse correlation between eotaxin mRNA⁺ cells and the histamine provocative concentration causing a 20% fall in FEV₁ (PC₂₀). Cytokeratin-positive epithelial cells and CD31⁺ endothelial cells were the major source of eotaxin mRNA whereas CCR3 co-localized predominantly to eosinophils. These data are consistent with the hypothesis that damage to the bronchial mucosa in asthma involves secretion of eotaxin by epithelial and endothelial cells resulting in eosinophil infiltration mediated via CCR3. Since selective (eotaxin) and non-selective C-C chemokines such as RANTES, MCP-3 and MCP-4 all stimulate eosinophils via CCR3, this receptor is potentially a prime therapeutic target in the spectrum of diseases involving eosinophil-mediated tissue damage.