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Biomedical subjects

M Bäckström

Publications and source records attributed to M Bäckström.

At least 19 recordsLinked to original sources

Historical pollution of seldom monitored trace elements in Sweden--Part A: sediment properties and chronological indicators.

Sediment cores from four small oligotrophic boreal lakes, with minor acidification, in remote regions of central Sweden were used for historical interpretation of their metal content, with focus on Cu, Cd, Pb and Zn in Lake Stensjön, which has the longest sediment record (at least two centuries according to (210)Pb dating). Comparison is made with the other three lakes. Major and trace elements in lake water, porewater and the acid-leached (HNO(3)) solid sediment phase was analysed with ICP-MS. In addition, general lake water chemistry, TOC and principal anions were measured in the aqueous phases. Redistribution processes were interpreted from geochemical modelling. The solid/solution distribution of pe/pH sensitive elements, indicates a minor diagenetic redistribution and the concentration profiles are therefore suitable for chronological evaluation. The ratios of Al, Ti, Sc and V, indicated a qualitative shift of sedimenting material a century ago, which did not have any impact on the retention of trace elements. Lead had a concentration profile, supported by the (206)Pb/(207)Pb ratio, where it was possible to distinguish preindustrial conditions, early industrialisation in Europe, industrialisation in Sweden, and the use of leaded petrol after the Second World War. Cadmium showed a similar concentration pattern. The zinc profile resembled that of cadmium, but with less enrichment. Local lithogenic sources are believed to be quantitatively important. The solid/solution distribution (K(d)) was independent of depth for all four elements. The sediment concentrations of copper and zinc are not related to early industrialisation but its concentration has doubled since the Second World War.

Environmental Monitoring↗

A small economic inducement to stimulate increased reporting of adverse drug reactions--a way of dealing with an old problem?

PURPOSE: To assess the effect of a small economic inducement on the rate of spontaneous reporting of adverse drug reactions (ADRs) and the attitudes of general practitioners and physicians towards reporting of ADRs. METHOD: One intervention and one control county were selected for the study. Written information about the main purpose of spontaneous reporting of ADRs was personally addressed to all physicians in the two counties. The information was identical, except for the addition that during a period of 6 months two lottery tickets would be given to the receivers in the intervention area with the standard personal feedback to the reporter of the ADR. After the 6-month study period, the actual number of reported ADRs and the seriousness of the reported ADRs were assessed. To investigate the attitude towards this stimulation of reporting, a questionnaire was addressed to all physicians within the intervention area (IA). RESULTS: From the IA a total number of 57 ADR reports were received containing 62 suspected ADRs, 40% of which were assessed as serious reactions. From the control area (CA), 49 reports containing 50 suspected ADRs were received, 32% of which were assessed as serious reactions. The increase of ADR reports from the IA compared to the same time period the previous year was 59% as compared to an unchanged reporting from the CA. Of those responding to the questionnaire, 80% did not believe that a small economic bonus would be a useful tool to improve the reporting rate. CONCLUSION: A small economic inducement is associated with an increase in the reporting of suspected ADRs.

Adverse Drug Reaction Reporting Systems↗

Bioprocess development for the production of a recombinant MUC1 fusion protein expressed by CHO-K1 cells in protein-free medium.

The mucin MUC1 is a candidate for use in specific immunotherapy against breast cancer, but this requires the large-scale production of a MUC1 antigen. In this study, a bioprocess for the expression of a recombinant MUC1 fusion protein with a cancer associated glycosylation in CHO-K1 cells has been developed. Cells permanently expressing parts of the extracellular portion of MUC1 fused to IgG Fc were directly transferred from adherent growth in serum-containing medium to suspension culture in the protein-free ProCHO4-CDM culture medium. Using the Cellferm-pro system, optimal culture parameter as pH and pO(2) were determined in parallel spinner flask batch cultures. A pH of 6.8-7.0 and a pO(2) of 40% of air saturation was found to give best cell growth and productivity of secreted recombinant protein. Specific productivity strongly depended the pO(2) and correlated with the online monitored oxygen uptake rate (OUR) of the cells, which indicates a positive influence of the rate of oxidative phosphorylation on productivity. The optimised conditions were applied to continuous perfusion culture which gave very high cell densities and space time yields of the recombinant MUC1 fusion protein, allowing production at gram scale. The product degradation was much lower in supernatants from continuous perfusion culture compared to batch mode. Antibodies reacting with cancer associated MUC1 glycoforms strongly bound to the fusion protein, indicating that the desired glycoforms were obtained and suggesting that the recombinant MUC1 protein could be tested for use in immunotherapy.

Animals↗

Under-reporting of serious adverse drug reactions in Sweden.

INTRODUCTION: Adverse drug reactions (ADR) constitute a major problem, both from a medical point of view and as an economical burden. Spontaneous reporting of ADRs is one of the methods for post marketing surveillance of drug safety. Under-reporting can also provide an important obstacle to rapid and relevant signal detection. AIM: To investigate the rate of under-reporting serious ADRs of selected ICD 10 diagnoses. METHOD: In order to investigate the under-reporting rate we investigated at five hospitals within the county of Norrbotten in Sweden the total number of diagnosed cases during a period of 5 years (1996-2000) with the following diagnoses: cerebral haemorrhage (I 61.0-I 61.9), pulmonary embolism (I 26.0 and I 26.9), embolism or thrombosis (I 74.0-I 74.9), phlebititis, thrombophlebitits or venous thrombosis (I 80.0-I 80.3, I 80.8 and I 80.9) and portal vein thrombosis and other thrombosis or emboli (I 82.0-I 82.3, I 82.8 and I 82.9). The identity of these patients was obtained through a database search. The patients' case records were then scrutinized by a specially trained nurse and the drugs used at the time of the event were noted. An assessment of the possibility of an ADR was performed using standard WHO causality criteria. Later, database search in the Swedish ADR registry was performed in order to investigate whether these suspected ADRs had been reported to the national authority in Sweden or not. RESULTS: In total 1349 case records were found and scrutinized. Of these, 107 patients had received drugs that could have been a probable or possible cause to the diagnoses. Of these 92 cases had not been reported and only 15 patients were found in the database, giving an overall under-reporting rate of all ADRs of 86%. The most commonly occurring diagnoses were cerebral haemorrhage followed by venous thrombosis, 545 and 468 respectively. Among those cases that should have been reported according to the existing rules for spontaneous reporting of suspected ADRs the most frequently occurring diagnosis was cerebral haemorrhage (I 61.0) in connection to treatment with anticoagulants. CONCLUSION: The rate of spontaneous ADR reporting is very low, also for serious and fatal reactions.

Adverse Drug Reaction Reporting Systems↗

Personality and self-variables: important determinants of subjective quality of life in schizophrenia out-patients.

OBJECTIVE: To investigate factors determining severely mentally ill patients' self-rated quality of life. The study hypothesized that objective life circumstances, personality, self-variables, and psychopathology would be determinants of quality of life. METHOD: A total of 117 individuals with schizophrenia and related disorders were investigated. Structural equation modelling was used to: 1). investigate if one or more subfactors best described the covariance within each potential determinant and quality of life, 2). explore the relations between all variables and factors extracted in step 1. RESULTS: A multi-factorial model indicated that a self-factor and two psychopathology factors worked as mediators of self-rated quality of life, in turn composed of an internal and an external aspect. Personality dimensions and objective life circumstances accounted directly or indirectly for substantial parts of quality of life. CONCLUSION: The relative importance of individual characteristics and objective indices was shown. Trait-like properties, such as the self-factor and personality, explained most of the variation in self-rated quality of life.

Adult↗

Seasonal variations in road runoff quality in Luleå, Sweden.

In regions with cold climate the urban drainage and highway runoff processes become much more complex, compared to temperate regions. Therefore, climatic conditions should be taken into account in planning and design of BMPs and snow handling strategies. In order to increase the knowledge of road runoff quality during melt and rain periods, respectively, measurements were carried out at a field site during a two-month period. The field site was situated at Södra Hamnleden, a road with 7,400 vehicles/day, in the central part of Luleå. Runoff samples were analysed for suspended solids and heavy metals (Pb, Cu, Cd, Ni and Zn). The results showed that the concentrations of suspended solids, lead, copper and cadmium were higher for the melt period, compared to rain generated runoff on the catchment without snow, and the highest concentrations were found during the rain-on-snow events. The results indicate a flow dependent increase in the concentration of suspended solids during the melt period. A comparison of the total mass of suspended solids over a one-month period showed that the melt period produced about 3 times more suspended solids. Metal elements during melt period were more particulate bound as compared to the rain period characterised by a higher percentage of the dissolved fraction.

Climate↗

Grassed swales for stormwater pollution control during rain and snowmelt.

The retention of suspended solids, particles and heavy metals in different grassed swales during rain events and snowmelt is discussed. The experimental results derived from investigations performed in existing grassed swales in the Luleå region, Northern Sweden. During high pollutant loading rates, grassed swales retain significant amounts of pollutants, mainly due to sedimentation of particulate matter. Low to moderate removal efficiencies could be expected for heavy metals, especially metals in solution (i.e. the dissolved phase). When grassed swales receive urban runoff with low pollutant concentrations, they may release rather than retain pollutants. Swales are important snow deposit areas in the city and particle bound pollutants do to a large extent remain in the swale after snowmelt. However, dissolved pollutants (i.e. dissolved heavy metals) are likely to escape the swale with the melt water. Grassed swales may be regarded as facilities that even out the peaks in pollutant loads without being capable of producing consistent high removal rates. This suggests that swales should be considered as primary treatment devices. Possible design parameters for grassed swales are mean hydraulic detention time, surface loading rate or specific swale area.

Biodegradation, Environmental↗

Spontaneous reporting of adverse drug reactions by nurses.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) remains one of the most effective methods to detect new and serious drug reactions. However, it is well known that there is a high degree of under-reporting. OBJECTIVE: This study was carried out as an attempt to improve and increase the reporting of ADRs by investigating the utility of nurses reporting in addition to physicians, as usual. METHODS: During a 12-month study period, nurses working at two departments of geriatric medicine in northern Sweden received special instruction regarding drugs and ADRs, ADR reporting and special aspects of ADRs in elderly people. The reports from the nurses were scrutinized concerning the seriousness of the reaction, reported drugs and type of reaction (type A or B). All nurses working at the two departments (117) were eligible to report but in practice only those attending the teaching sessions did so. A comparison with historical reporting and with reporting from other geriatric departments in Sweden was also carried out. At the end of the study all participating nurses received a questionnaire aimed at investigating their attitudes towards ADR reporting. RESULTS: After the 12-month study period 18 ADR reports involving 22 reactions had been received. Seven of these were assessed as serious reactions. All of the reactions were of type A. In comparison, during the corresponding time period from the study clinics during the preceding year, only two reports were registered. During the study period only 15 reports were registered from the other 50 geriatric departments in Sweden. CONCLUSION: Even though the total number of ADR reports was small, our data indicate a substantial increase in the reporting rate. This indicates that instructed and interested nurses could play an important role in detecting and reporting suspected ADRs.

Adverse Drug Reaction Reporting Systems↗

Sediment transport in grassed swales during simulated runoff events.

Particle trapping in nine different grassed swales was measured successfully with a standardised runoff event simulation procedure. The percentage of total suspended solids removed ranged from 79 to 98%. It was found that sedimentation processes, rather than grass filtration governed the overall particle trapping efficiency. The highest particle trapping efficiency was observed in the field swales with dense, fully developed turf. A high infiltration rate was beneficial for the particle trapping and an increased swale length made it possible for smaller particles to be captured. A densely vegetated, ten metre long swale, receiving a stormwater flow of 1.0 litres per second, may capture a majority of the waterborne particles with settling velocities larger than 0.1 metres per hour. A simple model of particle trapping efficiency in grassed swales was developed and tested. It was found that mean swale residence time could be used as a design parameter for particle removal in grassed swales. The suggested exponential relationship between mean swale residence time and particle settling velocity associated with a certain trapping efficiency is so far only valid for a limited range of swale designs and residence times.

Environmental Monitoring↗

Measuring adult attachment: a construct validation of two self-report instruments.

This study reports the Swedish construct validation of two translated attachment style scales. The factor structure of the attachment construct was investigated via exploratory and confirmatory factor analyses of attachment scores from 515 students of a Swedish university. Results supported the expected two-factor solution, but found a three-factor solution to be a viable alternative. In addition, the attachment scales were compared with the Big Five personality inventory (NEO-PI), using a sample of 87 Swedish students, and found to have expected correlation to this scale.

Adult↗

Novel carbohydrate binding site recognizing blood group A and B determinants in a hybrid of cholera toxin and Escherichia coli heat-labile enterotoxin B-subunits.

The B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) are structurally and functionally related. However, the carbohydrate binding specificities of the two proteins differ. While both CTB and LTB bind to the GM1 ganglioside, LTB also binds to N-acetyllactosamine-terminated glycoconjugates. The structural basis of the differences in carbohydrate recognition has been investigated by a systematic exchange of amino acids between LTB and CTB. Thereby, a CTB/LTB hybrid with a gain-of-function mutation resulting in recognition of blood group A and B determinants was obtained. Glycosphingolipid binding assays showed a specific binding of this hybrid B-subunit, but not CTB or LTB, to slowly migrating non-acid glycosphingolipids of human and animal small intestinal epithelium. A binding-active glycosphingolipid isolated from cat intestinal epithelium was characterized by mass spectrometry and proton NMR as GalNAcalpha3(Fucalpha2)Galbeta4(Fucalpha3)Glc NAcbeta3Galbeta4Glc NAcbeta3Galbeta4Glcbeta1Cer. Comparison with reference glycosphingolipids showed that the minimum binding epitope recognized by the CTB/LTB hybrid was Galalpha3(Fucalpha2)Galbeta4(Fucalpha3)GlcNAc beta. The blood group A and B determinants bind to a novel carbohydrate binding site located at the top of the B-subunit interfaces, distinct from the GM1 binding site, as found by docking and molecular dynamics simulations.

ABO Blood-Group System↗

Attitudes to reporting adverse drug reactions in northern Sweden.

OBJECTIVES: This study was designed to investigate attitudes of general practitioners (GPs) and hospital physicians in Sweden towards spontaneous reporting of adverse drug reactions (ADRs). METHOD: Two areas in the northern region of Sweden were selected for the study. A knowledge and attitude questionnaire followed by a reminder letter 2 weeks later was addressed to all GPs and hospital physicians in the study areas. RESULT: The total response rate from the study areas was 748 of the 1274 questionnaires sent out (58.7%). Of those who responded, 236 were GPs, 433 were hospital physicians and 79 had other positions. Of the responders, 252 stated that they had never reported any ADR and 488 that they had reported at least once in their career. Issues that came out as important in the decision to report or not to report were whether the reaction was considered well-known or not, the severity of the reaction, hesitance to report only on suspicion, lack of knowledge of existing rules, giving priority to other matters and lack of time to report ADRs. Only minor differences in these regards were observed between male and female physicians. CONCLUSION: Our investigation shows that the physicians in northern Sweden have a fairly good knowledge about the existing rules for reporting ADRs in Sweden. However, the attitudes leave room for considerable under-reporting due to matters related mainly to the medical impact of the reaction and of reporting it, but also to the scientific "paradox" of reporting only on suspicion and of course due to lack of time in the health care setting.

Adult↗

Determination of nitrate and other water quality parameters in groundwater from UV/Vis spectra employing partial least squares regression.

The use of UV/Vis spectroscopy in combination with partial least squares (PLS) regression for the simultaneous prediction of nitrate and non-purgeable organic carbon (NPOC) in groundwaters was evaluated. A model of high quality was obtained using first order derivative spectra in the range 200-300 nm. Inclusion of non-UV-absorbing constituents in the modeling procedure, i.e., chloride, sulfate, fluoride, total carbon (TC), inorganic carbon (IC), alkalinity, pH and conductivity was also evaluated. This model seemed to be useful for prediction of chloride, TC, IC, alkalinity and conductivity, while its ability to predict sulfate, fluoride and pH was poor. In conclusion, application of PLS regression, which requires neither filtration of samples nor addition of chemicals, is a promising alternative for fast interpretation of geochemical patterns of groundwater quality.

Fluorides↗

[Good quality of life after heart surgery. Comparable ratings by patients and their relatives].

In a series of 83 patients undergoing coronary artery bypass grafting for angina, perceived QOL (quality of life) was rated by the patients and their spouses, preoperatively and at two and 12 months postoperatively, using the SWED-QUAL instrument. One year after surgery, QOL had improved to a level which might be expected of a normal population comparable in age and gender distribution. Good correlation existed between patient and spouse ratings, especially on physical measures.

Angina Pectoris↗

S100beta after coronary artery surgery: release pattern, source of contamination, and relation to neuropsychological outcome.

BACKGROUND: S100beta has been suggested as a marker of brain damage after cardiac operation. The aim of this study was to characterize the early S100beta release in detail and relate it to neuropsychological outcome. METHODS: Three groups of patients were investigated. All patients underwent coronary artery bypass surgery (CABG) with extracorporeal circulation. In group A, 110 patients had sampling of S100beta for the first 10 postoperative hours and also underwent neuropsychological testing. In group B, 14 patients were examined for the effect of autotransfusion on S100beta levels. Eight patients in group C had their intraoperative bleeding processed with a cell-saving device. RESULTS: Group A had a heterogeneous release pattern with several rapid elevations in S100beta concentration. In group B, high concentrations of S100beta were found in the autotransfusion blood (range 0.2 to 210 microg/L) with a concurrent elevation of serum S100beta levels after transfusion of shed blood. In group C, high levels of S100beta were found in the blood from the surgical field (12.0+/-6.0 microg/L) and decreased (1.1+/-0.64 microg/L) after wash. Group C had significantly lower S100beta values at the end of cardiopulmonary bypass compared to group A (0.53+/-0.35 microg/L versus 2.40+/-1.5 microg/L). S100beta values were corrected for extracerebral contamination with a kinetic model. With this correction, an association was found between adverse neuropsychological outcome and S100beta release in group A (r = 0.39, p < 0.02). CONCLUSIONS: A significant amount of S100beta is found both in the blood from the surgical field and in the shed mediastinal blood postoperatively. Infusion of this blood will result in infusion of S100beta into the blood and interfere in the interpretation of early systemic S100beta values.

Blood Transfusion, Autologous↗

Structural basis for differential receptor binding of cholera and Escherichia coli heat-labile toxins: influence of heterologous amino acid substitutions in the cholera B-subunit.

The closely related B-subunits of cholera toxin (CTB) and Escherichia coli heat-labile enterotoxin (LTB) both bind strongly to GM1 ganglioside receptors but LTB can also bind to additional glycolipids and glycoproteins. A number of mutant CT B-subunits were generated by substituting CTB amino acids with those at the corresponding positions in LTB. These were used to investigate the influence of specific residues on receptor-binding specificity. A mutated CTB protein containing the first 25 residues of LTB in combination with LTB residues at positions 94 and 95, bound to the same extent as native LTB to both delipidized rabbit intestinal cell membranes, complex glycosphingolipids (polyglycosylceramides) and neolactotetraosylceramide, but not to non-GM1 intestinal glycosphingolipids. In contrast, when LTB amino acid substitutions in the 1-25 region were combined with those in the 75-83 region, a binding as strong as that of LTB to intestinal glycosphingolipids was observed. In addition, a mutant LTB with a single Gly-33-->Asp substitution that completely lacked affinity for both GM1 and non-GM1 glycosphingolipids could still bind to receptors in the intestinal cell membranes and to polyglycosylceramides. We conclude that the extra, non-GM1 receptors for LTB consist of both sialylated and non-sialylated glycoconjugates, and that the binding to either class of receptors is influenced by different amino acid residues within the protein.

Amino Acid Sequence↗