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Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 37 records · Page 2Linked to original sources

Chest pain and ischaemic heart disease in primary care.

BACKGROUND: Chest pain is the main symptom of first presentation with ischaemic heart disease (IHD). Little is known about the incidence of IHD among patients consulting the general practitioner (GP) for chest pain. AIMS: To estimate the occurrence of IHD among patients consulting for chest pain, to study the results of the bicycle exercise test, and to estimate the incidence of IHD in the population. DESIGN OF STUDY: Prospective descriptive study. SETTING: Three primary health centres in south-eastern Sweden. METHOD: All patients without a current IHD diagnosis, aged 20 to 79 years, and consulting for a new episode of chest pain, were included consecutively. The outcome was classified as IHD, possible IHD or not IHD, according to the results of a postal questionnaire, an exercise test or hospital care. Data from the hospital registry on patients with a diagnosis of IHD were analysed retrospectively. RESULTS: Out of 38,075 GP consultations, 577 (1.5%) were for chest pain. IHD was diagnosed in 41 (8%) of the chest pain patients, in 441 (83%) the diagnosis was excluded, and in 50 (9%) the diagnosis was judged as being uncertain. Even though the diagnostic criteria were strict, the exercise tests led to a diagnostic conclusion in 77% of the cases, most frequently a normal test result. Combining data from primary and hospital care, the yearly incidence of IHD was 6.5 diagnosed per 1000 inhabitants (aged 20 to 79 years old). CONCLUSION: The incidence of a new episode of chest pain bringing the patients to the GP was low. Eight per cent of the patients received an IHD diagnosis, and in 9% further investigation or clinical assessment is needed.

Adult↗

HLA in coeliac disease families: a novel test of risk modification by the 'other' haplotype when at least one DQA1*05-DQB1*02 haplotype is carried.

Predisposition to coeliac disease (CD) involves HLA genes. We investigated whether any haplotypes modify risk when carried trans to a known high-risk haplotype, DQA1*05-DQB1*02. Earlier attempts to rank levels of risk contributed by the 'other' haplotype were burdened by use of case-control populations; haplotype frequencies were estimated and homozygosity was only presumed. In contrast, exact haplotypes can be determined and allele transmission can be traced in families. A similar study in narcolepsy reported strata of different degrees of predisposition, attributable to the 'other' haplotype. A gene dosage effect similar to that described for DQB1*02 in CD, has also been reported in narcolepsy. We genotyped 439 simplex/multiplex trios for DQA1 and DQB1. We designed a new statistic to test risk modulation by the trans haplotype, even if the affected offspring was homozygous. We tested for significant deviation in transmission of the 'other' haplotype, i.e., modification of DQA1*05-DQB1*02 risk. We also addressed the proposed difference in risk, between DQA1*05-DQB1*02 homozygotes and DQA1*05-DQB1*02/DQA1*0201-DQB1*02 heterozygotes, reported in Southern Europe. We confirmed a DQB1*02 gene dosage effect. However, no haplotypes were found to modify risk when carried trans to DQA1*05-DQB1*02, except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02 which were already known. We did not find credible evidence for a difference in risk conferred by DQA1*05-DQB1*02 and DQA1*0201-DQB1*02, when carried with DQA1*05-DQB1*02. The new test, which directly inspects haplotype transmissions rather than estimated haplotype frequencies, was used to demonstrate that the 'other' haplotype (except DQA1*05-DQB1*02 and DQA1*0201-DQB1*02) does not modify risk conferred by DQA1*05-DQB1*02. The test is applicable to other diseases.

Celiac Disease↗

Consumption of added fats and oils in the European Prospective Investigation into Cancer and Nutrition (EPIC) centres across 10 European countries as assessed by 24-hour dietary recalls.

OBJECTIVE: To evaluate the consumption of added fats and oils across the European centres and countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN AND SETTING: 24-Hour dietary recalls were collected by means of standardised computer-guided interviews in 27 redefined EPIC centres across 10 European countries. SUBJECTS: From an initial number of 36 900 subjects, single dietary recalls from 22 924 women and 13 031 men in the age range of 35-74 years were included. RESULTS: Mean daily intake of added fats and oils varied between 16.2 g (Varese, Italy) and 41.1 g (Malmö, Sweden) in women and between 24.7 g (Ragusa, Italy) and 66.0 g (Potsdam, Germany) in men. Total mean lipid intake by consumption of added fats and oils, including those used for sauce preparation, ranged between 18.3 (Norway) and 37.2 g day-1 (Greece) in women and 28.4 (Heidelberg, Germany) and 51.2 g day-1 (Greece) in men. The Mediterranean EPIC centres with high olive oil consumption combined with low animal fat intake contrasted with the central and northern European centres where fewer vegetable oils, more animal fats and a high proportion of margarine were consumed. The consumption of added fats and oils of animal origin was highest in the German EPIC centres, followed by the French. The contribution of added fats and oils to total energy intake ranged from 8% in Norway to 22% in Greece. CONCLUSIONS: The results demonstrate a high variation in dietary intake of added fats and oils in EPIC, providing a good opportunity to elucidate the role of dietary fats in cancer aetiology.

Adult↗

Consumption of dairy products in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: data from 35 955 24-hour dietary recalls in 10 European countries.

OBJECTIVES: To describe and compare the consumption of dairy products in cohorts included in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Data from single 24-hour dietary recall interviews collected through a highly standardised computer-based program (EPIC-SOFT) in 27 redefined centres in 10 European countries between 1995 and 2000. From a total random sample of 36 900, 22 924 women and 13 031 men were selected after exclusion of subjects under 35 and over 74 years of age. RESULTS: A high total consumption of dairy products was reported in most of the centres in Spain and in the UK cohort sampled from the general population, as well as in the Dutch, Swedish and Danish centres. A somewhat low consumption was reported in the Greek centre and in some of the Italian centres (Ragusa and Turin). In all centres and for both sexes, milk constituted the dairy sub-group with the largest proportion (in grams) of total dairy consumption, followed by yoghurt and other fermented milk products, and cheese. Still, there was a wide range in the contributions of the different dairy sub-groups between centres. The Spanish and Nordic centres generally reported a high consumption of milk, the Swedish and Dutch centres reported a high consumption of yoghurt and other fermented milk products, whereas the highest consumption of cheese was reported in the French centres. CONCLUSION: The results demonstrate both quantitative and qualitative disparities in dairy product consumption among the EPIC centres. This offers a sound starting point for analyses of associations between dairy intake and chronic diseases such as cancer.

Adult↗

Evaluations of the stability of sheathless electrospray ionization mass spectrometry emitters using electrochemical techniques.

The processes that cause the failure of sheathless electrospray ionization (ESI) emitters, based on different kinds of gold coatings on fused-silica capillaries, are described and explained. The methods chosen for this study include electrochemical methods, ICPMS analysis of the electrolytes used, SEM studies, and electrospray experiments. Generally, the failure occurs by loss of the conductive coating. It is shown that emitters with sputter-coated gold lose their coatings because of mechanical stress caused by the gas evolution accompanying water oxidation or reduction. Emitters with gold coatings on top of adhesion layers of chromium and nickel alloy withstand this mechanical stress and have excellent durability when operating as cathodes. When operating as anodes, the adhesion layer is electrochemically dissolved through the gold film, and the gold film then flakes off. It is shown that the conductive coating behaves as a cathode even in the positive electrospray mode when the magnitude of a superimposed reductive electrophoretic current exceeds that of the oxidative electrospray current. Fairy-dust coatings developed in our laboratory (see Barnidge, D. R.; etal.Anal. Chem. 1999, 71, 4115-4118,) bygluing gold dust onto the emitter, are unaffected by the mechanical stress due to gas evolution. When oxidized, the fairy-dust coatings show an increased surface roughness and decreased conductivities due to the formation of gold oxide. The resistance of this oxide layer is however negligible in comparison with that of the gas phase in ESI. Furthermore, since no flaking and only negligible electrochemical etching of gold was found, practically unlimited emitter lifetimes may be achieved with fairy-dust coatings.

Journal Article↗

Rat-mouse and rat-human comparative maps based on gene homology and high-resolution zoo-FISH.

The laboratory rat, Rattus norvegicus, and the laboratory mouse, Mus musculus, are key animal models in biomedical research. A deeper understanding of the genetic interrelationsships between Homo sapiens and these two rodent species is desirable for extending the usefulness of the animal models. We present comprehensive rat-human and rat-mouse comparative maps, based on 1090 gene homology assignments available for rat genes. Radiation hybrid, FISH, and zoo-FISH mapping data have been integrated to produce comparative maps that are estimated to comprise 83-100% of the conserved regions between rat and mouse and 66-82% of the conserved regions between rat and human. The rat-mouse zoo-FISH analysis, supported by data for individual genes, revealed nine previously undetected conserved regions compared to earlier reports. Since there is almost complete genome coverage in the rat-mouse comparative map, we conclude that it is feasible to make accurate predictions of gene positions in the rat based on gene locations in the mouse.

Animals↗

[A case report: young man survived penetrating knife stabs to the heart and lung].

In Sweden, penetrating injuries to the lung and especially to the heart are fortunately rare. We hereby present a case-report on a young man who was stabbed in the right lung and heart. The paramedics arrived at the scene one minute after the alarm and instituted mechanical ventilation and fluid infusion. Ten minutes later the young man arrived at the emergency department. By then the patient was in deep shock without spontaneous breathing, was darkly cyanotic, showed indeterminately palpable pulses and non-reacting pupils. ECG-monitoring showed sinus-rhythm. Massive fluid infusion was initiated and the adolescent was immediately transported to the operating room. On the way to the operating room the patient's heart arrested. A lateral thoracotomy was performed to relieve the cardiac tamponade, and internal heart massage was initiated. Injuries to the lung and heart were reached through sternotomy. Thanks to prompt initial handling by the paramedics and emergency personnel, a trauma-trained senior surgeon and rather direct lines of communication at the small hospital, the young man could return to ordinary activities with neither physical nor neurological deficit.

Adolescent↗

A role for estrogen receptor beta in the regulation of growth of the ventral prostate.

In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor beta (ERbeta). In rat ventral prostate, 530- and 549-aa isoforms of the receptor were identified. These sediment in the 4S region of low-salt sucrose gradients, indicating that prostatic ERbeta does not contain the same protein chaperones that are associated with ERalpha. Estradiol (E(2)) binding and ERbeta immunoreactivity coincide on the gradient, with no indication of ERalpha. In prostates from mice in which the ERbeta gene has been inactivated (BERKO), androgen receptor (AR) levels are elevated, and the tissue contains multiple hyperplastic foci. Most epithelial cells express the proliferation antigen Ki-67. In contrast, prostatic epithelium from wild-type littermates is single layered with no hyperplasia, and very few cells express Ki-67. Rat ventral prostate contains an estrogenic component, which comigrates on HPLC with the testosterone metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol). This compound, which competes with E(2) for binding to ERbeta and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but does not affect the elevated levels seen in ERbeta knockout (BERKO) mice. Thus ERbeta, probably as a complex with 3betaAdiol, is involved in regulating the AR content of the rodent prostate and in restraining epithelial growth. These findings suggest that ligands specific for ERbeta may be useful in the prevention and/or clinical management of prostatic hyperplasia and neoplasia.

Androstane-3,17-diol↗

Microparticles for selective protein determination in capillary electrophoresis.

A system for detection of trace amounts of protein was developed. Two different monoclonal antibodies against human chorionic gonadotropin (hCG) were covalently bound to latex particles. When the latex particles were mixed with a sample containing hCG, a latex-protein-latex complex (immunocomplex) was formed. The complex was separated from the single latex particles using capillary electrophoresis and detected using UV-Vis detection. Limit of detection was 8 amol hCG. The separation was also monitored in real time using laser induced fluorescence - charge coupled device (LIF-CCD) imaging detection. However, a limitation of the method is the restriction to detection of proteins for which monoclonal antibodies are available.

Antibodies, Monoclonal↗

Molecularly imprinted microparticles for capillary electrochromatography: studies on microparticle synthesis and electrolyte composition.

The use of molecularly imprinted polymer (MIP) microparticles in a partial filling application of capillary electrochromatography (CEC) has previously been shown successful for the enantiomer separation of propranolol. In this investigation, the influence of some important parameters in the preparation protocol, i.e., template to monomer ratio, type of cross-linker and functional monomers, and the effect of separation condition, i.e., organic modifier content, pH and the temperature of the column, on the electrochromatographic behavior of the MIP microparticles were studied. It was found that ethyleneglycol dimethacrylate (EDMA), having two reactive double bonds, was superior in terms CEC performance to trimethylpropane trimethacrylate (TRIM) and pentaerythritol tetraacrylate (PETEA) having three and four double bonds, respectively. The use of weak functional monomers, i.e., monomers lacking a strong interaction with the template, was shown to increase the separation efficiency. It was found that the template to functional monomer ratio had a pronounced influence on the MIP microparticle partial filling CEC performance as well as the size of the obtained microparticles. The use of a partial filling technique realizes the use of a new MIP phase in every new separation as well as the ability of altering the selectivity of the separation column and length of the MIP without the need for column switching.

Adrenergic beta-Antagonists↗

Approaches to molecular imprinting based selectivity in capillary electrochromatography.

The work done during the past decade in order to adapt molecularly imprinted polymers (MIPs) to the capillary format and subsequently use these highly selective matrices for capillary electrochromatography (CEC) are reviewed in this article. MIPs are prepared utilizing a templated polymer synthesis where the template addresses the selectivity of the resulting polymer. These polymers possess binding characteristics that are comparable to the biological antibodies. Due to the polyclonality of the binding sites in the MIP, the separation result in severe peak broadening and tailing when performed in the isocratic mode. This was seen early in the development of MIPs as selective stationary phases in liquid chromatography (LC). As a mean of decreasing these problems, much effort was put into adapting the MIP to fit in CEC systems, that offers an efficiency that is superior to that in LC. Aiming to increase the efficiency of the MIP-CEC systems, different MIP formats have been developed that can be divided into three conceptually different categories, i.e., the monolithic, the microparticle and the coating. The strive for MIP formats that can be used in small bore capillaries has led to the development of MIP formats applicable to miniaturized systems approaching the chip format. Although prepared in order to perform MIP-CEC mediated separations, these formats can be used in a broad range of applications were the characteristics of the MIP, e.g. stability, selectivity and cost efficiency, could offer an interesting solution to cover the needs.

Chromatography, Micellar Electrokinetic Capillary↗

A simple and robust conductive graphite coating for sheathless electrospray emitters used in capillary electrophoresis/mass spectrometry.

A graphite-polyimide mixture was used as a conductive coating for sheathless electrospray emitters. The coating procedure described is simple and inexpensive compared to previously described methods. An investigation of the stability of the conductive coating carried out by electrochemical methods revealed good performances during oxidative stress. In addition, no decrease in emitter performance was seen during continuous electrospray in the positive electrospray mode for two weeks. Fast capillary electrophoresis with attomole sensitivity demonstrated the excellent performance of the described sheathless interface when used in conjunction with an orthogonal time-of-flight mass spectrometer. The overall simplicity, stability and low cost of this type of sheathless emitter make the described approach highly suitable for any on-column coupling of low flow rate separation techniques to a mass spectrometer.

Journal Article↗

Risk factors for epithelial borderline ovarian tumors: results of a Swedish case-control study.

OBJECTIVE: Borderline ovarian tumors have a favorable prognosis. Previous epidemiological studies indicate common risk factors for invasive epithelial ovarian cancers and borderline tumors, but it remains unresolved whether these tumors are precursors of invasive cancers or a separate disease entity. The objective of this population-based case-control study conducted in 1993-1995 was to examine reproductive and other factors in relation to the risk of borderline ovarian tumors. METHODS: Subjects were 193 histologically verified incident epithelial borderline tumor cases and 3899 randomly selected controls aged 50-74 years, whose data were collected through mailed questionnaires. Risk estimates were calculated by unconditional logistic regression. RESULTS: Ever parous women were at reduced risk, with odds ratios of 0.44 (95% confidence interval (CI) 0.26-0.75) for serous and 0.63 (95% CI 0.34-1.19) for mucinous tumors. No clear trends emerged for age at first birth, at menarche, and at menopause. Lactation reduced tumor risk. Oral contraceptive ever use conferred no protection, with odds ratios of 1.40 (95% CI 0.87-2.26) for serous and 1.04 (95% CI 0.61-1.79) for mucinous tumors. The odds ratio for serous tumors following unopposed estrogen ever use was 2.07 (95% CI 1.08-3.95), whereas no risk increase appeared with estrogens supplemented by cyclic or continuous progestins. Mucinous tumors were not associated with hormone replacement therapy. The odds ratio for serous tumors in the highest category of body mass index was 6.47 (95% CI 3.09-13.5). CONCLUSIONS: Increasing parity and lactation reduce the risk of borderline ovarian tumors in women aged 50-74, while no protection follows oral contraceptive use. Hormonal situations such as unopposed estrogen use and obesity, where estrogens are not counteracted by progestins, may increase the risk of serous tumors.

Aged↗

Radioimmunoscintigraphy using an anti-prostate monoclonal antibody (E4): a dosimetric evaluation.

The aim of this study was to evaluate different strategies to increase the tumour radiation dose for experimental radioimmunotherapy using 125I-labelled monoclonal antibody (MAb) E4 in a nude mice model xenografted with DU-145 tumours. The effects from a single injection of the 125I-labelled MAb E4, the same total amount of radiolabelled MAb E4 divided into three repeated injections, and the effect of pre-targeting with non-labelled MAb E4 for reducing the amount of shed antigen were investigated. Based on repetitive quantitative radioimmunoscintigraphies, calculation of the tumour radiation dose delivered from the 125I-nuclide was performed for each strategy. The single injection strategy without pretargeting rendered the highest mean tumour radiation dose, i.e. 0.23 Gy/MBq. Pretargeting with non-labelled MAb E4 before a single injection of [125I]E4 resulted in a slightly lower mean tumour radiation dose, i.e. 0.19 Gy/MBq, compared to the single injection alone. An even lower mean tumour radiation dose, i.e. 0.14 Gy/MBq, was obtained when the same total administered amount of activity was divided into three separate injections given in 10-day intervals. We concluded that the single injection strategy is the most efficient when using MAb E4 in this tumour model. The tumour radiation doses were not increased by dividing the same amount of activity into three injections or by pretargeting with non-labelled MAb E4.

Animals↗

The diagnosis of bacterial vaginosis and vaginal flora changes.

In a population of 956 women, attending for contraceptive advice, 131 (13.7%) were found to have BV acording to Amsel's criteria. Clue cells were detected in 200 (20.9%) women, a positive amine ('sniff') test in 191 (20.0%), a vaginal pH > or = 4.7 in 243 (25.4%) and a "characteristic" vaginal discharge in 104 (10.9%) women. Sensitivity, specificity, positive and negative predictive values in relation to BV were calculated for each of these four criteria. The detection of clue cells, an increased pH and a positive sniff test showed excellent sensitivity (86-100%) values, but had a less satisfactory positive predictive value (52-68%). Vaginal discharge was found to be a poor predictor of BV. The vaginal flora in women with clue cells, increased vaginal pH or a positive sniff test was very similar to that of the women with BV, every after excluding concomitant cases of BV and the three respective criteria. Thus, a positive amine test, which is easily performed, strongly suggests BV and a vaginal flora predominated by Gardnerella vaginalis, Mycoplasma hominis, Mobiluncus species and anaerobic species on one hand, and lack of lactobacilli on the other. When there is a clinical suspicion of BV, the sniff test is positive and differential diagnoses are excluded, one can safely treat a woman for bacterial vaginosis.

Adult↗

Technetium-99m labelling of glycosylated somatostatin-14.

This study presents a technetium-99m labelling method based on organometallic chemistry. It describes the simple mixing of a 99mTc(I)-carbonyl compound [99mTc(OH2)3(CO)3]+ with a histidine-tagged somatostatin-dextran (SMS-Dx-His) conjugate. Somatostatin and histidine was coupled to periodate activated dextran. The linkage was stabilised by reductive amination. The conjugate was then radiolabelled with 99mTc by using the 99mTc(CO)3 core. The labelling efficiency was 65-80% and the radiochemical purity > 95%. In the in vitro cysteine challenge, the result showed that 25% of the radiolabel was released after 1 h incubation at 37 degrees C (cysteine-conjugate at 1000:1 molar ratio). The radiolabelled SMS-Dx-His showed similar HPLC profile as the unlabelled conjugate. This labelling method, employing non reducing conditions, is useful for the labelling of peptides containing disulphide bonds. It should be possible to be used also for labelling with rhenium-188 for therapeutic applications.

Chromatography, High Pressure Liquid↗

Selective estrogen receptor modulators and coronary heart disease.

The vasculature has been recognized as an important target of estrogen action through rapid non-genomic effects and/or via the classic pathway (genomic effects) involving estrogen receptors (ER-alpha and ER-beta). Multiple mechanisms participate in the regulation of different estrogen-controlled genes, providing a wide spectrum of possibilities for development of drugs, including pure agonists or antagonists or mixed agonists/antagonists, the so-called selective estrogen receptor modulators (SERM). In theory, an ideal SERM should reduce the risks of coronary heart disease (CHD) and preserve bone density, without or with very low incidences of breast and endometrial neoplasms or venous thromboembolism (VTE). The precise mechanism for the protective effects of estrogens and their receptors on cardiovascular diseases is not yet fully established. In this review, we summarize the recent advances in understanding the action of ERs/ligands, the therapeutic implications for CHD, and highlight the recent progress of both clinical and basic studies on the protection issue. Finally, a number of newly developed SERMs and their clinical applications as well as the laboratory investigations are discussed.

Animals↗