Inhaled and oral bronchodilator therapy in exercise induced asthma

Measurements of peak expiratory flow rate during serial exercise tests were used to assess the efficacy of the beta adrenergic stimulants oral terbutaline (5 mg) and fenoterol aerosol (400 micrograms), in preventing post-exercise bronchoconstriction in 18 asthmatic subjects. While both compounds significantly elevated resting levels of peak expiratory flow rate for at least four hours, there were qualitative and quantitative differences in the effects of the two drugs on exercise induced bronchoconstriction. Oral terbulation did not significantly alter the pattern of response to exercise. However, the peak expiratory flow rates before during and after exercise were significantly higher compared with placebo at two, four and six hours after the drug. The importance of examination of actual values for peak expiratory flow rates as well as percentage changes when testing oral bronchodilators is emphasised. Aerosol fenoterol completely blocked post-exercise bronchoconstriction immediately after inhalation and for up to four hours in most subjects. Bronchodilatation occurred in all subjects during exercise in the presence of both the active and placebo drugs. It is postulated that the superiority of the aerosol in blocking exercise induced bronchoconstriction may be function of its activity at the surface of the bronchial mucosa.     

Thrombolytic therapy in stroke. What do clinical tests prove?

Despite the increased risk of intracranial haemorrhage associated with the use of thrombolytic treatment of stroke. American studies have shown patients treated with rt-PA (recombinant plasminogen activator) within three hours of the onset of symptoms to manifest 30 per cent less disability at three-month follow-up than those placebo. However, until satisfactory criteria for the use of rt-PA are available, caution is essential, and thrombolytic therapy should be restricted to specialised centres. It is also important to promote public awareness of the stroke patient's need of immediate treatment at a specialised stroke unit.     

Efficient autoproteolytic processing of the MHV-A59 3C-like proteinase from the flanking hydrophobic domains requires membranes

The replicase gene of the coronavirus MHV-A59 encodes a serine-like proteinase similar to the 3C proteinases of picornaviruses. This proteinase domain is flanked on both sides by hydrophobic, potentially membrane-spanning, regions. Cell-free expression of a plasmid encoding only the 3C-like proteinase (3CLpro) resulted in the synthesis of a 29-kDa protein that was specifically recognized by an antibody directed against the carboxy-terminal region of the proteinase. A protein of identical mobility was detected in MHV-A59-infected cell lysates. In vitro expression of a plasmid encoding the 3CLpro and portions of the two flanking hydrophobic regions resulted in inefficient processing of the 29-kDa protein. However, the efficiency of this processing event was enhanced by the addition of canine pancreatic microsomes to the translation reaction, or removal of one of the flanking hydrophobic domains. Proteolysis was inhibited in the presence of N-ethylmaleimide (NEM) or by mutagenesis of the catalytic cysteine residue of the proteinase, indicating that the 3CLpro is responsible for its autoproteolytic cleavage from the flanking domains. Microsomal membranes were unable to enhance the trans processing of a precursor containing the inactive proteinase domain and both hydrophobic regions by a recombinant 3CLpro expressed from Escherichia coli. Membrane association assays demonstrated that the 29-kDa 3CLpro was present in the soluble fraction of the reticulocyte lysates, while polypeptides containing the hydrophobic domains associated with the membrane pelletes. With the help of a viral epitope tag, we identified a 22-kDa membrane-associated polypeptide as the proteolytic product containing the amino-terminal hydrophobic domain.     

Time-frequency analysis using the matching pursuit algorithm applied to seizures originating from the mesial temporal lobe

A Spanish-language questionnaire designed for measuring the impact of asthma on quality of life in adults was developed. It was derived, by the application of a rigorous translation protocol, from a previously validated, English-language Asthma Quality of Life (AQL) questionnaire which had been developed in Australia. The aim of this study was to evaluate the psychometric properties of the Spanish AQL questionnaire using a cross-sectional and longitudinal design. Two hundred ninety-four clinically stable subjects with asthma (168 women, mean baseline forced expiratory volume in 1 sec [FEV1] = 85% predicted), aged 17-70, attended for the initial baseline assessment. All subjects completed the AQL questionnaire and a full history and physical examination were performed. The clinical assessment of severity was based on the classification recommended by the Global Initiative on Asthma (GINA). One week after the initial assessment subjects completed the AQL questionnaire for a second time. Six months later, subjects were assessed clinically and completed all the assessment measures at baseline. Principal components analysis of the AQL questionnaire responses at the baseline visit revealed a structure that was almost identical to that seen in the original English-language questionnaire. The questionnaire was shown to be internally consistent (Cronbach's alpha 0.91 for total score and 0.80-0.86 for the four subscales) and repeatable (intraclass correlation coefficient 0.91 for the total scale and 0.78-0.92 for the subscales). The finding of expected strong correlations with the subject's global assessment of severity (p = 0.70) and dyspnea (p = 0.63), a weak inverse correlation with FEV1 (p = -0.17), and good discrimination among the four GINA severity categories (F3,291 = 37.16, p < 0.0001) supports the construct validity of the questionnaire. AQL scores increased with age (p = 0.31) and were higher in women (p < 0.005). The AQL was responsive to both improvement (mean change 1.02, p < 0.0001) and deterioration (mean change -1.13, p < 0.001) in the severity of asthma over a 6-month period. This disease-specific, Spanish-language AQL questionnaire was shown to have sound psychometric properties which make it suitable for use in cross-sectional or longitudinal studies where it is appropriate to assess the impact of asthma on the quality of life of individual patients.