The case of diagnostic imaging in European Union during the 1990s.
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Diagnostic Imaging↗
Biomedical subjects
S Olsson
Publications and source records attributed to S Olsson.
Degradation of acenaphthene, phenanthrene and pyrene in a packed-bed biofilm reactor.
Biofilm reactors are particularly suitable for the treatment of large amounts of diluted effluent, such as groundwater contaminated with scarcely soluble pollutants. A packed-bed column reactor was tested for the degradation of acenaphthene, phenanthrene and pyrene provided at their aqueous solubility concentrations. Acenapthene and phenanthrene were removed to more than 99% efficiency from this reactor whilst pyrene was removed to 90%. Pollutant disappearance was also recorded in the control reactor and was probably caused by the adsorption of pollutants into the reactor. The measurement of oxygen consumption in both reactors confirmed that microbial degradation of the pollutants was indeed occurring in the inoculated reactor. Physical adsorption is not however unwanted, as it could help with the formation of a biofilm at an early stage of the treatment.
Acenaphthenes↗
Allergens from house dust and storage mites: similarities and differences, with emphasis on the storage mite Lepidoglyphus destructor.
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Allergens↗
Skin prick test and serological analysis with recombinant group 2 allergens of the dust mites L. destructor and T. putrescentiae.
BACKGROUND: The dust mites Lepidoglyphus destructor and Tyrophagus putrescentiae are important sources of allergen in farming environments. The major allergens of the dust mites L. destructor and T. putrescentiae have been cloned and expressed as recombinant proteins. OBJECTIVE: To evaluate the use of recombinant group 2 allergens of L. destructor (rLep d 2) and T. putrescentiae (rTyr p 2) in skin prick test (SPT), and serological analysis in sensitized and non-sensitized farmers chronically exposed to dust mites. METHODS: Skin prick test with rLep d 2, rTyr p 2 and the corresponding commercial extracts was performed in 44 farmers sensitized to L. destructor and/or T. putrescentiae, and 38 control farmers. IgE and IgG subclass antibodies to the recombinant allergens were analysed by RAST and ELISA, respectively. RESULTS: Out of the 44 subjects positive in SPT to L. destructor and/or T. putrescentiae extract, 26 (59%) displayed a positive SPT to one or the other of the recombinant allergens, whereas 21 (48%) were positive to both. Significant correlations were registered between the sizes of the weals induced by rLep d 2 and rTyr p 2 and the corresponding RAST values (P < 0.001). A majority of subjects positive in SPT to the recombinant allergens had detectable IgG4 antibodies, and the levels were significantly higher in the dust mite sensitized group than in the controls (P < 0.05). No such differences were found in the IgG1 values (P > 0.05). The results obtained with rLep d 2 and rTyr p 2 correlated relatively well with each other with respect to SPT, RAST and IgG4, suggesting that the allergens have similar or shared IgE epitopes. All the control subjects had a negative SPT and RAST to rLep d 2 and rTyr p 2. CONCLUSION: Recombinant group 2 allergens from the dust mite L. destructor and T. putrescentiae represent useful tools for diagnosis of dust mite allergy.
Adult↗
Direct microscopy of bacillus endospore germination in soil microcosms.
Antagonistic endospore-forming Bacillus spp. offer a large potential as seed inoculants for control of soil-borne pathogens. In the soil, however, inoculated Bacillus endospores may remain dormant without germination, and plant protection can therefore be inefficient and unpredictable. A method based on direct fluorescence microscopy in soil microcosms was used to determine whether low-cost organic additives incorporated into seed coating material could stimulate endospore germination. Complex organic additives supported a high level of endospore germination of the fungal antagonist Paenibacillus polymyxa CM5-5. Skim milk is a low-cost additive that may be incorporated into seed coating material for efficient induction of Bacillus endospore germination in soil.
Alanine↗
Implementation of service screening with mammography in Sweden: from pilot study to nationwide programme.
Establishment of mammography screening in Sweden has progressed logically from pilot study through clinical trials to service screening. Screening with mammography for early detection of breast cancer has been provided by all Sweden's 26 county councils since 1997. It took 23 years from the initial pilot study through clinical trials to the establishment of mammography service screening throughout Sweden. In the screening rounds completed by 1995-96, and provided by all but one county council, 1040000 women participated, corresponding to 81% of those invited. The national average recall rate was 2.2%, and consequently 23000 women were recalled for additional investigations. Eleven county councils invited women aged 40-74, six invited women aged 50-69, the remaining eight invited women between both these age intervals. Mammography outside screening programmes-clinical mammography-is available throughout Sweden. About 100000 women a year were referred for clinical mammography and about 50% of these were either younger or older than those invited for screening. A negative relation between the use of clinical mammography and participation in the screening programmes was noticed.
Adult↗
[Health care within the research program of the EU for 1999-2002: age-related diseases and public health are prioritized].
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Aged↗
[Integrity of young abortion applicants is overestimated].
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Abortion Applicants↗
Evaluation of specific IgE to the recombinant group 2 mite allergens Lep d 2 and Tyr p 2 in the Pharmacia CAP system.
BACKGROUND: Several recombinant allergens have been shown to be potentially useful for diagnosis of IgE-mediated allergy, but only a few recombinant allergens are at present commercially available in serological assays for detection of specific IgE. The aim of this study was to evaluate the IgE binding to the recombinant major dust mite allergens rLep d 2 and rTyr p 2 and compare it with the IgE binding to the commercial mite extracts Lepidoglyphus destructor and Tyrophagus putrescentiae in the Pharmacia RAST CAP System. METHODS: The recombinant allergens rLep d 2 and rTyr p 2 were immobilised on ImmunoCAPs, and sera from 461 Swedish farmers who are frequently exposed to mites were analysed for specific IgE antibodies. Immunoblotting was performed to evaluate discrepancies between the results obtained with the recombinant and the commercial CAP assays. RESULTS: The IgE values of each recombinant assay significantly correlated with the IgE values of the corresponding commercial CAP assay. The sensitivity of the rLep d 2 assay was 73.3% and that of the rTyr p 2 assay, 60.5% of that provided by the commercial L. destructor and T. putrescentiae assays. Two subjects out of 416, who tested negative in the commercial L. destructor assay, were positive to rLep d 2. The corresponding figures for rTyr p 2 and the T. putrescentiae extract were 5/418. The possibility that these subjects were sensitised to L. destructor and T. putrescentiae could not be excluded. CONCLUSIONS: The data suggest that it may be possible to use rLep d 2 and rTyr p 2 on ImmunoCAPs to detect and quantify IgE antibodies to these, the major allergens of L. destructor and T. putrescentiae. It appears likely that the addition of just a few more recombinant L. destructor and T. putrescentiae allergens in the CAP assay will be sufficient for in vitro diagnosis of IgE mediated allergy to L. destructor and T. putrescentiae.
Allergens↗
A conditionally immortalized epithelial cell line for studies of intestinal drug transport.
A new cell culture model that better mimics the permeability of the human small intestine was developed for studies of passive drug transport. The intestinal epithelial cell line, 2/4/A1, conditionally immortalized with a temperature-sensitive mutant of the growth-promoting oncogene simian virus 40 (SV40) large T, was grown on permeable supports. The cells grew at 33 degrees C, where the oncogene is fully active, but stopped growing and entered a differentiation program at 39 degrees C, where the oncogene is inactive. Significant cell death was observed at 39 degrees C and, therefore, growth conditions under which 2/4/A1 cells survive during the differentiation process were developed. Cells grown on extracellular matrices which contained laminin at an intermediate temperature of 37 degrees C formed viable differentiated monolayers with tight junctions, an increased expression of brush border enzymes, and a paracellular permeability that was comparable to that of the human small intestine. The permeability of 17 structurally diverse drugs gave a sigmoidal relationship with the absorbed fraction of the drugs after oral administration to humans. The relationship was compared with those obtained with the well established Caco-2 model and after in vivo perfusion of the human jejunum. The transport of drugs with low permeability in 2/4/A1 monolayers was comparable to that in the human jejunum, and up to 300 times faster than that in Caco-2 monolayers. The transport of drugs with high permeability was comparable in all models. These results indicate that 2/4/A1 monolayers are promising alternatives to Caco-2 monolayers for studies of passive drug transport.
Animals↗
A Bayesian neural network method for adverse drug reaction signal generation.
OBJECTIVE: The database of adverse drug reactions (ADRs) held by the Uppsala Monitoring Centre on behalf of the 47 countries of the World Health Organization (WHO) Collaborating Programme for International Drug Monitoring contains nearly two million reports. It is the largest database of this sort in the world, and about 35,000 new reports are added quarterly. The task of trying to find new drug-ADR signals has been carried out by an expert panel, but with such a large volume of material the task is daunting. We have developed a flexible, automated procedure to find new signals with known probability difference from the background data. METHOD: Data mining, using various computational approaches, has been applied in a variety of disciplines. A Bayesian confidence propagation neural network (BCPNN) has been developed which can manage large data sets, is robust in handling incomplete data, and may be used with complex variables. Using information theory, such a tool is ideal for finding drug-ADR combinations with other variables, which are highly associated compared to the generality of the stored data, or a section of the stored data. The method is transparent for easy checking and flexible for different kinds of search. RESULTS: Using the BCPNN, some time scan examples are given which show the power of the technique to find signals early (captopril-coughing) and to avoid false positives where a common drug and ADRs occur in the database (digoxin-acne; digoxin-rash). A routine application of the BCPNN to a quarterly update is also tested, showing that 1004 suspected drug-ADR combinations reached the 97.5% confidence level of difference from the generality. Of these, 307 were potentially serious ADRs, and of these 53 related to new drugs. Twelve of the latter were not recorded in the CD editions of The physician's Desk Reference or Martindale's Extra Pharmacopoea and did not appear in Reactions Weekly online. CONCLUSION: The results indicate that the BCPNN can be used in the detection of significant signals from the data set of the WHO Programme on International Drug Monitoring. The BCPNN will be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs.
Adverse Drug Reaction Reporting Systems↗
Contribution of disulphide bonds to antigenicity of Lep d 2, the major allergen of the dust mite Lepidoglyphus destructor.
To study the contribution of the 3 disulphide bonds in the major allergen Lep d 2 to the antigenic structure, site-directed mutagenesis was performed. Mutants with one or more cysteine residues altered were constructed with a histidine residue tag for purification purposes and expressed as recombinant proteins in E. coli. Seven mutants were analysed: 3 single mutants (Cys 8, Cys 21 and Cys 72), 3 double mutants (Cys 8-117, Cys 21-16 and Cys 72 77) and one mutant with all 6 cysteines altered (6 Cys). The evaluation of IgE reactivity in 10 allergic patients showed that the disulphide bond formed by cysteine 72 and 77 was the single most contributing bond to IgE binding. Mutants with disruption of the Cys 8-117 bond had a lesser reduction in IgE binding, even though this alteration seemed to influence the compact nature of Lep d 2. However, to abolish the IgE reactivity almost completely, all 6 cysteines had to be altered. A monoclonal antibody previously raised against Lepidoglyphus destructor showed a similar binding as human IgE with no reactivity to the Cys 72 77 or the 6 Cys mutant. Using skin prick test we found no reaction to the 6 Cys mutant at the concentrations tested (1-100 microg/ml) in an Lepidoglyphus destructor allergic patient, while the T-cell reactivity was preserved. The 6 Cys mutant of Lep d 2 may, after further evaluation, be a candidate molecule for improved immunotherapy of Lepidoglyphus destructor allergy.
Allergens↗
Expression of two isoforms of Lep d 2, the major allergen of Lepidoglyphus destructor, in both prokaryotic and eukaryotic systems.
BACKGROUND: The dust mite Lepidoglyphus destructor is a major cause of allergic diseases among farmers. We have previously cloned and sequenced two isoforms of the major allergen Lep d 2 (formerly designated Lep d 1) and found significant homology to group 2 allergens of the house dust mite species Dermatophagoides. We now report on the production and characterization of recombinant Lep d 2. OBJECTIVE: We have expressed both isoforms in two different expression systems; a eukaryotic system, baculovirus in insect cells and a prokaryotic system, E. coli. We have compared the two systems in regard to production yields and immunoreactivity of the recombinant allergens. METHODS: The complete cDNA including the natural leader sequence was cloned into the pBlueBacIII transfer vector, and the rLep d 2 was produced as a secreted protein in baculovirus. For the expression in E. coli, the cDNA was cloned into the pET vector, and the rLep d 2 was produced with six C-terminal histidine residues. The purified recombinant allergens were tested for immunoreactivity with 10 sera from subjects allergic to Lepidoglyphus destructor and were compared with native Lep d 2 using inhibition immunoblotting. The ability of the recombinant allergens to release histamine from basophils was evaluated using a histamine release assay. RESULTS: Both expression systems produced immunoreactive recombinant allergens. They inhibited the binding of human sera to native Lep d 2 confirming their retained IgE binding properties. The yield of pure recombinant protein from the prokaryotic system was approximately 1 mg/L compared to the eukaryotic system which produced up to 4 mg/L in an adherent cell culture system. CONCLUSIONS: We have produced recombinant Lep d 2 in prokaryotic and eukaryotic expression systems which are comparable to the native allergen. Recombinant Lep d 2 might now be included in more extensive clinical studies to confirm its usefulness in the in vitro and the in vivo diagnosis of Lepidoglyphus destructor.
Allergens↗
The role of the WHO programme on International Drug Monitoring in coordinating worldwide drug safety efforts.
The rationale for setting up the WHO International Programme for Adverse Reaction Monitoring, 30 years ago was to make it possible to identify rare adverse drug reactions (ADRs) that could not be found through clinical trial programmes. It became evident that maintaining an international database of ADR case reports and a network of institutions and scientists concerned with drug safety issues provides great additional gains when compared with operating in isolation. Thus, the scope of the WHO programme has expanded over time to accommodate the expansion of the field of drug safety monitoring, now often named pharmacovigilance. The international centre, the WHO Collaborating Centre for International Drug Monitoring in Uppsala [now known as the Uppsala Monitoring Centre (UMC)], maintains the international database and serves the national centres associated with the WHO programme; however, the role of the centre is expanding allowing it to play a leading role in global drug safety monitoring. The national centres are appointed by the governments of each of the countries participating in the WHO programme. These centres are responsible for collecting spontaneous ADR reports originating from health professionals, 49 countries are currently contributing case information and are full members of the programme; an additional 11 countries have applied for membership but have still not submitted any reports. The annual influx of reports is currently fluctuating at around 150,000 reports. In its development, the data collected by the WHO programme was guarded by strong rules of confidentiality. In some member countries, however, case data, with the important exception of reporter and patient identities, has always been public information. The UMC has made it a priority to try to create an atmosphere of openness and trust between all parties involved in drug safety assessment, which will eventually enable general sharing of available data and an extended analysis and use of the data collected. The WHO network represents the wealth of competence and experience that is at the disposal of countries wishing to join the international pharmacovigilance community.
Adverse Drug Reaction Reporting Systems↗
No Effects of Acute Alcohol Ingestion on Subjective Visual Horizontal Determination During Eccentric Rotation.
Evaluating the function of the vestibular part of the inner ear comprises more than the classic analysis of the lateral semicircular canal function. In healthy subjects, positional alcohol nystagmus may be seen after acute alcohol ingestion. Posturography has shown a deteriorated equilibrium after even moderate doses of alcohol, which speculatively could be an effect of otolith disturbance or a central integrative effect. We tested the possibility of an otolith effect by using linear acceleration in the lateral direction by means of eccentric rotation, stimulating mainly the outermost ear's otolith organ. The subject is seated eccentrically in a rotatory chair facing the direction of rotation. Thus, the otolith organs are stimulated in steady-state rotation. The subject experiences a lateral tilt and, in darkness, is instructed to put a short light bar in the position thought to be that of a water surface, which is identical to the perceived tilt. Twenty healthy subjects (10 men, 10 women) aged 20-29 years were tested before and approximately 1 hour after ingestion of alcohol, the amounts consumed corresponding to an approximate blood alcohol level of 0.05%, well above the maximum permissible level for driving in Sweden. No significant effects of alcohol were found. The otolith function probably is not affected by moderate alcohol intoxication levels. From this point of view, equilibrium deterioration due to alcohol ingestion in the erect position is caused by a central integrative deficit and not by an otolith effect.
Journal Article↗
Subjective Visual Horizontal Determination During Otolith Stimulation by Eccentric Rotation in Conservatively Treated Meniere's Disease.
Peripheral vestibular equilibrium disorders may originate in various parts of the labyrinth or of the vestibular nerve. Traditionally, the function of the lateral semicircular canals has been assessed by caloric irrigation and has been interpreted (sometimes falsely) as demonstrating a vestibular nerve lesion. The vertical semicircular canals are not assessed easily. Caloric testing with the head in various positions is not very helpful, but the canals may be tested in pairs using specific rotational techniques. Often, the otolith organs, detecting linear acceleration forces, are forgotten as a source of vertigo and dizziness. The extent of otolith involvement in Meniere's disease is not well understood. The tested subject is seated eccentrically in a rotatory chair and faces the direction of rotation. Thus, the otolith organs are stimulated in steady-state rotation. The subject experiences a lateral tilt and, in darkness, is instructed to point a short light bar in the position that he or she thinks a water surface would have (identical to the perceived tilt). Patients with conservatively treated unilateral Meniere's disease were tested. In the eccentric rotation test, the patients with unilateral Meniere's disease showed highly variable, sometimes even paradoxical, responses. No correlation was noted between the eccentric otolith test and pure-tone audiometry or the side difference of the caloric responses. Otolith and lateral semicircular canal functions may differ in patients with Meniere's disease, the nature of which remains to be elucidated in further studies.
Journal Article↗
Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement.
PURPOSE: It has recently been shown that the absorption enhancing and toxic effects of chitosans are dependent on their chemical composition. In this study, the mechanisms underlying these effects were investigated at the cellular level. METHODS: The effects on epithelial cells of chitosans with different chemical composition, absorption enhancing properties and toxicities were studied in Caco-2 monolayers. Chitosan C( 1:31) has a low degree of acetylation (DA) (1%) and a low m.w. (31 kD), and displays dose-dependent absorption enhancement and cytotoxicity; chitosan C(35:170) has a higher DA (35%) and a higher m.w. (170 kD), is less dose-dependent in absorption enhancement, and is not cytotoxic. A third non-toxic chitosan C(49:22) with a high DA (49%), a low m.w. (22 kD), and no influence on epithelial permeability was used as control. RESULTS: C(1:31) and C(35:170) bound tightly to the epithelium. Cellular uptake of the chitosans was not observed. Both chitosans increased apical but not basolateral cell membrane permeability and induced a redistribution of cytoskeletal F-actin and the tight junction protein ZO-1. This resulted in increased paracellular permeability of hydrophilic marker molecules of different molecular weights. Addition of negatively charged heparin inhibited the cellular and the absorption enhancing effects of the chitosans, indicating that these effects are mediated via their positive charges. The onset of the effects of C(35:170) on apical membrane permeability and tight junction structure was much faster than that of C(1:31). C(49:22) did not influence any of the properties of the Caco-2 cell monolayers studied. CONCLUSIONS: The binding and absorption enhancing effects of chitosans on epithelial cells are mediated through their positive charges. The interaction of chitosans with the cell membrane results in a structural reorganisation of tight junction-associated proteins which is followed by enhanced transport through the paracellular pathway.
Biomarkers↗
Information complexity--mental workload and performance in combat aircraft.
The purpose of the present study was to analyse the effects of information complexity on Pilot Mental WorkLoad (PMWL) and Pilot Performance (PP), and to analyse the structure of PMWL. Eighteen pilots performed 72 simulated low level-high speed emissions. The complexity of the Head Down Display (HDD) information varied as a function of the tactical situation. Flight data were recorded continuously. The pilots' eye movements were video taped and psychophysiological activation data, Heart Rate (HR), were obtained. The pilots rated PMWL according to the psychological content of three scales (Bedford Rating Scale, Subjective Workload Assessment Technique, NASA-Task Load indeX) and answered a questionnaire tapping aspects of performance, information load, motivation and mood. It was found that even a moderate complexity of information interfered with the flight task. Altitude and variation in altitude were increased and corrections of altitude errors were delayed, when complexity increased. Changes in information load reached its maximum influence on flight performance (r = 0.60, p < 0.001) after a time delay of 20 to 40 seconds. Performance of the flight task correlated positively (r = 0.59, p <0.001) with the performance of the information handling task (Tactical Situation Awareness, TSA). Durations and frequencies of eye fixations Head Up (HU) versus Head Down (HD) changed as a function of information load. A structural equation model implied that PMWL was affected by mission complexity and that PMWL affected objective and subjective aspects of flight performance and information handling. Heart rate (sortie means) correlated positively with PMWL (r = 0.34, p <0.05) and perceived complexity of mission (r = 0.37, p < 0.01). Heart rate (running means) covaried with variations in information complexity for those pilots who performed well. From spectral analyses of cardiac interval times it was found that the amplitude of the 0.10 Hz component tended to decrease during high as compared to low levels of information load.
Adult↗