Technical validation of an autoantibody test for lung cancer.

BACKGROUND: Publications on autoantibodies to tumour-associated antigens (TAAs) have failed to show either calibration or reproducibility data. The validation of a panel of six TAAs to which autoantibodies have been described is reported here. MATERIALS AND METHODS: Three separate groups of patients with newly diagnosed lung cancer were identified, along with control individuals, and their samples used to validate an enzyme-linked immunosorbant assay. Precision, linearity, assay reproducibility and antigen batch reproducibility were all assessed. RESULTS: For between-replicate error, samples with higher signals gave coefficients of variation (CVs) in the range 7%-15%. CVs for between-plate variation were only 1%-2% higher. For between-run error, CVs were in the range 15%-28%. In linearity studies, the slope was close to 1.0 and correlation coefficient values were generally >0.8. The sensitivity and specificity of individual batches of antigen varied slightly between groups of patients; however, the sensitivity and specificity of the panel of antigens as a whole remained constant. The validity of the calibration system was demonstrated. CONCLUSIONS: A calibrated six-panel assay of TAAs has been validated for identifying nearly 40% of primary lung cancers via a peripheral blood test. Levels of reproducibility, precision and linearity would be acceptable for an assay used in a regulated clinical setting.

Impact of nurse-led outpatient management of children with asthma on healthcare resource utilisation and costs.

The high burden of asthma on healthcare utilisation and costs warrants economic appraisal of management approaches. The authors previously demonstrated that the efficacy of nurse-led outpatient management of childhood asthma was comparable to management by a paediatrician and now report on the healthcare utilisation and costs of both management approaches. A total of 74 newly referred children with asthma were randomly assigned to a 1-yr follow-up by paediatricians or asthma nurse. Healthcare utilisation was recorded and associated costs calculated for both management approaches. There were no significant differences in healthcare utilisation except for the total time spent on patient contact (136(n = 14) versus 187(n = 41) min, for patients followed-up by paediatrician and an asthma nurse repectively). Costs within the healthcare sector were reduced by 7.2% in favour of nurse-led care. The reduction in costs was solely attributable to a 17.5% reduction in the costs of outpatient visits. Nurse-led care appeared to be cost-saving even if the duration of follow-up visits would be twice that of doctor's visits. Overall healthcare costs (within and outside the healthcare sector) were 4.1% lower for nurse-led outpatient management compared to traditional medical care. Nurse-led outpatient management of childhood asthma can be provided at a lower cost than medical care by paediatricians.

Outpatient management of childhood asthma by paediatrician or asthma nurse: randomised controlled study with one year follow up.

BACKGROUND: Until now, care provided by asthma nurses has been additional to care provided by paediatricians. A study was undertaken to compare nurse led outpatient management of childhood asthma with follow up by a paediatrician. METHODS: Seventy four children referred because of insufficient control of persistent asthma were randomly allocated to 1 year follow up by a paediatrician or asthma nurse. The main outcome measure was the percentage of symptom-free days. Additional outcome measures were airway hyperresponsiveness, lung function, daily dose of inhaled corticosteroids (ICS), number of exacerbations, number of additional visits to the general practitioner, absence from school, functional health status, and disease specific quality of life. RESULTS: There were no significant differences at the end of the 1 year study period between the two treatment groups in percentage of symptom-free days (mean difference 2.5%; 95% CI -8.8 to 13.8), airway hyperresponsiveness (log10 PD20 0.06; -0.19 to 0.32), functional health status (10.1; -0.3 to 19.8), disease specific quality of life of patients (0.08; -0.9 to 0.7), and disease specific quality of life of caregivers (0.09; -0.2 to 0.3), nor in any other outcome parameters. Most outcome parameters improved considerably over the 1 year study period. These improvements were achieved although the daily dose of ICS was reduced by a mean of 26% compared with the dose received by children at referral. All parents were satisfied with the asthma care received. CONCLUSIONS: After initial assessment in a multidisciplinary clinic, childhood asthma can be successfully managed by an asthma nurse in close cooperation with a paediatrician. During close follow up by paediatrician or asthma nurse, asthma control improved despite a reduction in ICS dose.

The social psychology of public response to warnings of a nuclear power plant accident.

This article reviews the process of public response to warnings of an impending nuclear power plant emergency. Significant evidence exists to suggest that people engage in protective action in response to warnings based upon the substance and course through which emergency warning information is disseminated. The three basic components of a warning system are defined, and the elements of public response to warnings are summarized. Popular myths about public response to warnings are outlined and dispelled based upon current research verification. The conclusion provides an overview and synthesis of the warning response process.

Overexpression, purification, and stereochemical studies of the recombinant (S)-adenosyl-L-methionine: delta 24(25)- to delta 24(28)-sterol methyl transferase enzyme from Saccharomyces cerevisiae.

The ERG6 gene that encodes (S)-adenosyl-L-methionine: delta 24(25)-to delta 24(28)-sterol methyl transferase (SMT) enzyme from Saccharomyces cerevisiae was introduced into plasmid pET23a(+) and the resulting native protein was overexpressed in BL21 (DE3) host cells under control of a T7 promoter. This enzyme was purified to apparent homogeneity by ammonium sulfate precipitation, anion exchange, and hydrophobic interaction chromatography. N-Terminal sequence analysis of the first 10 amino acids of the purified SMT protein confirmed the identity of the start triplet and expected primary structure. The enzyme exhibited a turnover number of 0.01/s and an isoelectric point of 5.95. A combination of Superose 6 chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the purified SMT enzyme possessed a native molecular weight of 172,000 and was tetrameric. The purified SMT enzyme generated kinetics in which velocity versus substrate curves relative to zymosterol (preferred sterol acceptor molecule) and AdoMet were sigmoidal rather than hyperbolic, indicating enzyme cooperativity among the subunits. Studies on product formation using [27-13C]zymosterol and [2H3-methyl]AdoMet incubated with the pure SMT enzyme confirmed the reaction mechanism of sterol methylation to involve a 1,2-hydride shift of H-24 to C-25 from the Re-face of the original 24,25- double bond. Deduced amino acid sequence comparisons of the SMT polypeptide from S. cerevisiae with related sterol methyl transferase enzymes of plant and fungal origin indicate that there is a significant degree of similarity between these enzymes. Specifically, there is a conserved sequence (in yeast from amino acids ca. 79 to 92 which contains an YEXGWG motif; referred to as Region I) that is not present in other AdoMet-dependent methyl transferase enzymes.

Treatment of insomnia in cancer patients using muscle relaxation training.

Mean sleep onset latency was reduced from 124 to 29 min in 15 patients suffering from insomnia secondary to cancer; 15 subjects receiving routine care had means of 116 and 104 min in comparison. Muscle relaxation training was administered in individual sessions on three consecutive days. With 26 subjects available for follow-up 3 months later, the mean differences in sleep latency continued. The relatively greater success in this study than previously reported for a behavioral treatment of insomnia is discussed in light of possible differences between primary insomniacs and those subjects with insomnia secondary to a medical disease.