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.     

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.     

Mobility and percussion sound of healthy upper incisors and canines.

In order to evaluate the correlation between mobility and percussion sound, 126 upper incisors and canines in 21 student volunteers were measured by means of the Periotest (Siemens), by evaluating the percussion sound subjectively and by analyzing its spectrum. The attenuation time and frequency of the sound were measured for each tooth. A logical mobility and percussion sound existed in accordance with the sizes of the teeth. Spearman correlation coefficients close to 1.00 were noted in individual cases between the Periotest and the three other tests describing the percussion sounds.     

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.     

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.     

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.     

Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens

The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.     

Real-time PCR for rapid diagnosis of entero- and rhinovirus infections using LightCycler.

BACKGROUND: PCR techniques have proved to be more sensitive than traditional cell culture in the diagnosis of enterovirus and rhinovirus infections and are widely used in clinical virus laboratories. However, PCR assays are relatively time-consuming and labor intensive, particularly if separate hybridization steps are used to confirm the specificity of positive findings. OBJECTIVES: The aim of the present study was to develop fast and sensitive real-time PCR assay, which would allow simultaneous detection of entero- and rhinoviruses and their quantification in clinical and experimental samples. STUDY DESIGN: Two real-time RT-PCR protocols were developed using LightCycler (LC) technology; SYBRGreen and hybridization probe assays. The sensitivity of these assays to detect entero- and rhinoviruses was compared with that of a traditional reference RT-PCR-hybridization assay and cell culture. All PCR protocols used the same primers amplifying the 5'-non coding region (NCR) of entero- and rhinoviruses. The LC probe assay and the reference RT-PCR used almost identical detection probes, which bind to enterovirus specific amplicons. RESULTS AND CONCLUSIONS: Both real-time PCR assays were equally sensitive as the reference RT-PCR-assay and all were more sensitive than cell culture. Both real-time assays quantified reliably the amount of the virus and took much shorter time than the reference RT-PCR. As the real-time SYBRGreen assay detects both entero- and rhinoviruses it can be used for primary screening of samples, which can be positive for either of these viruses. The real-time probe-assay can confirm the presence of enterovirus in SYBRGreen positive samples or it can be used for selective screening of enteroviruses e.g. from CSF samples.     

Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment

BACKGROUND: In several clinical studies, topical calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis (AD). They target signaling pathways that control gene expression, particularly the expression of cytokines. OBJECTIVE: We examined the cellular infiltrate in skin lesions of 10 patients with AD and characterized the cytokine pattern expressed by the infiltrating cells before and after short-term topical therapy with tacrolimus 1% ointment. METHODS: Skin biopsies were examined for histologic alterations (hematoxylin and eosin staining), composition of the cellular inflammatory infiltrate (immunofluorescence), and cytokine expression (ribonuclease protection assay, ELISA, immunofluorescence) before as well as 1 and 3 weeks after initiation of tacrolimus therapy. For comparison, biopsies from nonlesional AD and normal skin were analyzed. Systemic immunologic effects were assessed by analyzing peripheral blood leukocytes (immunofluorescence) as well as in vitro stimulated pan-T-cell cytokine production (ELISA). RESULTS: All patients showed a significant improvement of their skin lesions associated with a marked regression of spongiosis, acanthosis, and density of the cellular infiltrate in the dermis. The last was a result of reduced infiltration of T cells, B cells, and eosinophils. In contrast, the numbers of mast cells did not change. Moreover, the expression of the T H 2 cytokines IL-5, IL-10, and IL-13 in CD4 + T cells was reduced after therapy. Interestingly, tacrolimus therapy was also associated with a reduction of CD8 + T cells expressing the T H 1 cytokine IFN-gamma. Furthermore, the numbers of epidermal CD1a + dendritic cells increased after treatment. In the peripheral blood, a decrease of granulocytes (eosinophils and neutrophils) but no changes in the distribution of lymphocyte subpopulations were noticed. CONCLUSION: Topical tacrolimus treatment has anti-inflammatory effects on AD skin as indicated by reduced infiltration of cytokine expressing inflammatory cells. No evidence for drug-induced systemic immunosuppression was obtained.