Reproducibility of Computerized Measurements of QT Interval from Multiple Leads at Rest and During Exercise

Background: Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. Methods: Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1–31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp‐e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. Results: Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp‐e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. Conclusions: The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions.     

A chimeric EGFR/neu receptor in functional analysis of the neu oncoprotein.

As the factor binding to the neu protein has been unknown, it has not been possible to confirm experimentally the proposed growth-factor receptor like functions of the neu protein. To approach this problem we constructed a recombinant receptor which enabled ligand regulation of the neu tyrosine kinase. The hybrid receptor consisted of the extracellular ligand binding, transmembrane and protein kinase C-substrate domains joined to the intracellular tyrosine kinase and carboxyl-terminal domains of the neu protein. Several properties of NIH3T3 cells carrying this construct were tested. We obtained the first experimental evidence that the neu proto-oncogene has mitogenic and transforming activities only in the presence of a ligand stimulating its tyrosine kinase activity. Various cellular and molecular biological parameters indicated that the chimeric receptor behaved very similarly to the EGFR. Also, this chimeric receptor has allowed us to compare the constitutive oncogenic and the ligand-activated non-oncogenic activities of the neu tyrosine kinase. In the future we plan to focus on characterization of possible differences between EGFR and neu signalling in more differentiated cellular backgrounds.     

Dynamics of lipid adsorption at the electrified water∣1,2-dichloroethane interface

A recently introduced setup to measure the dynamic interfacial tension of expanding drops was used to compare the adsorption behaviour of a series of lipids at the electrified water∣dichloroethane interface. Phospholipids with saturated carbon chains of different length (DMPC, DPPC, DSPC, DAPC, DBPC), an unsaturated phospholipid (DOPC) and an ethanolamine (DSPE) were compared. It was found that the adsorption decreases with increasing chain length. Also, the increase of the flow rate reduces the degree of adsorption effectively. On the timescale of the experiments, the DSPE, DAPC and DBPC adsorption showed no potential dependence, whereas the adsorption of DOPC was stronger than that of the saturated lipids. Adsorption was modelled using the Langmuir adsorption isotherm; the potential dependence of adsorption is discussed.     

Intra- and interfraction breathing variations during curative radiotherapy for lung cancer.

BACKGROUND AND PURPOSE: This study aimed at quantifying the breathing variations among lung cancer patients over full courses of fractionated radiotherapy. The intention was to relate these variations to the margins assigned to lung tumours, to account for respiratory motion, in fractionated radiotherapy. MATERIALS AND METHODS: Eleven lung cancer patients were included in the study. The patients' chest wall motions were monitored as a surrogate measure for breathing motion during each fraction of radiotherapy by use of an external optical marker. The exhale level variations were evaluated with respect to exhale points and fraction-baseline, defined for intra- and interfraction variations respectively. The breathing amplitude was evaluated as breathing cycle amplitudes and fraction-max-amplitudes defined for intra- and interfraction breathing, respectively. RESULTS: The breathing variations over a full treatment course, including both intra- and interfraction variations, were 15.2mm (median over the patient population), range 5.5-26.7mm, with the variations in exhale level as the major contributing factor. The median interfraction span in exhale level was 14.8mm, whereas the median fraction-max-amplitude was 6.1mm (median of patient individual SD 1.4). The median intrafraction span in exhale level was 1.6mm, and the median breathing cycle amplitude was 4.0mm (median of patient individual SD 1.4). CONCLUSIONS: The variations in externally measured exhale levels are larger than variations in breathing amplitude. The interfraction variations in exhale level are in general are up to 10 times larger than intrafraction variations. Margins to account for respiratory motion cannot safely be based on one planning session, especially not if relying on measuring external marker motion. Margins for lung tumours should include interfraction variations in breathing.     

Localized pleural plaques and lung cancer.

In a mass chest radiography survey conducted in 1971 for 7,986 residents of three Finnish communities, 604 subjects (7.6%) with pleural plaques but not other asbestos-related radiographic signs were identified. The same number of referents, each individually matched to each plaque carrier on sex, birth year, and community, was selected from among persons in the same source population with no pleural plaques. The two groups were followed for investigation of incidence of lung cancer during 1972-1989. Twenty-eight of those with plaques and 25 referents contracted lung cancer (crude conditional RR = 1.1; CL95 = 0.7, 1.9). The application of the proportional hazards model, with adjustment for sex, age, and residence, resulted in a hazard ratio of 1.1 (CL = 0.6, 1.8). The risk ratio estimate may be biased; hence, the result is inconclusive in regard to the predictive assessment of lung cancer risk among carriers of pleural plaques.     

Logics and Logistics of Community Intervention Against Osteoporosis: An Evidence Basis

Under designations like small areas action research and intervention, directed ‘ground-up’ health promotion and prevention in the population form an important part of the ongoing medical systems development. There is recent evidence of the success of community intervention against cardiovascular disease. In osteoporosis, however, there is still a lack of conclusive data on both the logics and logistics of such an approach. Since 1988, a county health policy program has been formulated and implemented in Östergötland, Sweden, following the principles and guidelines of the WHO HFA 2000 declaration. Vadstena (n ? 7,600) was chosen for a local and generalizable osteoporosis prevention project mediated by the primary care organization by means of health promotion and education in the community. In the present report we emphasize that community intervention is an important new advancement of the medical systems, where the basic research questions include operational and management aspects as equally vital and measurable requisites and results as other performance and outcome variables. We found that a community intervention trial against osteoporosis is both motivated and feasible and in this report wish to provide evidence on these crucial issues of logics and logistics.     

Patency of the infarct-related coronary artery — a pertinent factor in late recovery of myocardial fatty acid metabolism among patients receiving thrombolytic therapy?

The decrease in mortality among patients receiving thrombolytic therapy for myocardial infarction is greater than would be expected from the improvement in left ventricular contractile function alone; thus some additional advantage of recanalization of the infarctrelated coronary artery probably exists. Changes in the post-infarction myocardial metabolic state with respect to artery patency have not been studied with a gamma camera previously. A single-photon emission tomography scan using the fatty acid analogue para-¹²³I-iodophenylpentadecanoic acid was performed at rest before hospital discharge on nine patients with first anterior myocardial infarction. All patients had received intravenous thrombolytic therapy at the beginning of the insult. The semiquantitative analysis of the left ventricle included a total of 44 segments in each patient. The test was repeated 3 months later, with the patients divided into two groups: six patients had an angiographically patent left anterior descending coronary artery (group A), and three an occluded artery (group B). In group A the number of myocardial segments with abnormal (<70% of maximum) fatty acid uptake was initially 20.2±4.7 (mean±SD) and was reduced to 11.3±6.1 during the follow-up (95% confidence interval of the decrease 16.0–1.7 segments). In group B the number of these aberrant segments was fairly constant (21.7±13.1, initial test, and 21.3±13.3, retest). Our preliminary results suggest that even when thrombolytic therapy fails to prevent myocardial infarction, myocardial fatty acid metabolism has a better change of recovering if the relevant coronary artery has regained its patency. This finding emphasizes the need for further study to establish whether a direct link exists between myocardial metabolic state and patient survival after infarction.     

Occupational allergic contact dermatitis and composition of acrylates in dentin bonding systems

Background Dentin-bonding systems contain sensitizing acrylates. They are increasingly used in dentistry, but only few cases of allergy have been encountered. Objective This study reports observations on eleven patients sensitized by acrylates in dentin-bonding compounds. Furthermore, the composition of dentin-bonding products was analysed and compared with the information given in the material safety data sheets. Methods Patch testing was performed to reveal allergic contact dermatitis, and chamber provocation tests to reveal possible respiratory sensitivity. Gas chromatography/mass spectrometry was used to analyse the chemical composition of the bonding products. Results The most common sensitizer in our material of eleven patients was 2-hydroxyethyl methacrylate (2-HEMA). Another putative sensitizer, BIS-GMA, used in dentin adhesives, did not cause sensitization. The typical allergic dermatitis localized to the fingertips (pulpitis). Seven of the eleven patients also developed paresthesia of the fingertips. One patient with positive patch test reactions to (meth)acrylates had pharyngitis hut no skin symptoms. One patient was sensitized because she had been patch tested with too high a concentration (undiluted) of dentin-bonding components. Material safety sheets gave inaccurate or wrong information about the contents. Conclusion Dentin-bonding acrylates are strong sensitizers, and even a single exposure may sensitize.