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Biomedical subjects

M Ekman

Publications and source records attributed to M Ekman.

At least 19 recordsLinked to original sources
PubMed2007

Resource use and costs associated with patients treated for depression in primary care.

We investigated medical resource consumption, productivity loss and costs associated with patients treated with antidepressants for depression in primary care in Sweden. Patients on treatment for depression were followed naturalistically for six-months, and data on patients' characteristics, daily activity and resource-use were collected. The total cost per patient was estimated at euro 5,500 (95%CI euro 5,000-6,100) over six months in 2005 prices. Direct costs were estimated at euro 1,900 (euro 1,700-2,200), 35% of total costs, and indirect costs at euro 3,600 (euro 3,100-4,100), 65% of total costs. The cost for antidepressants represented only 4% of the total costs. We conclude that the burden of depression is high, both to the individual as well as to wider society, and there seems to be a particular need for therapies that have the potential to improve productivity in depressed patients.

Adolescent↗
PubMed2007

Impact of different inhibitor reactivities with commercial factor VIII concentrates on thrombin generation.

In order to describe the haemostatic role of a variation in inhibitor reactivity with different factor VIII (FVIII) concentrates, we have compared inhibitor titres against a panel of FVIII concentrates and correlated titre with the capacity to inhibit thrombin generation. Three plasma-derived concentrates were tested in vitro in mixing experiments with inhibitor plasmas from 11 patients with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF) with a final ratio of approximately 1:1 (VWF IU per IU FVIII:C); Haemate-P with a ratio of 2.5:1 and Hemofil-M containing only trace amounts of VWF. In addition, the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included. Inhibitor titres and the capacity to generate thrombin were measured. A statistically significant difference in measured titres was found with the highest titres recorded against Hemofil-M. The inhibitor titres needed to inhibit 50% maximum thrombin generation were the lowest for Kogenate Bayer and the highest and similar for Fanhdi and Haemate-P with intermediate titres needed for inhibition of Hemofil-M. In this study, the thrombin generation assay provides additional indications for the role of VWF in the treatment of patients with inhibitors. The VWF-containing concentrates Fanhdi and Haemate-P, added to FVIII-deficient plasma with the presence of inhibitor, generate more thrombin than do the purified concentrates Hemofil-M and Kogenate Bayer.

Antigen-Antibody Reactions↗
PubMed2006

The mission is remission: health economic consequences of achieving full remission with antidepressant treatment for depression.

The aim of the present study was to determine the magnitude of the impact of treating depression to full remission on cost and health-related quality of life. In a naturalistic longitudinal survey recordings of resource use and quality of life were carried out among depressed patients treated with antidepressant therapy in 56 Swedish primary care clinics. We found that a total of 52% of the patients achieved full remission during the study period. Remitting patients had, on average, three outpatient visits less than non-remitting patients (p < 0.01), 22 fewer sick leave days (p = 0.01), which translated into a significantly lower total cost (Euro 2700) compared with non-remitting patients (p < 0.01). Health-related quality-of-life scores improved by 40% for remitting patients when compared with non-remitting ones (p < 0.01). We conclude that remission has a substantial health economic impact on patients treated for depression, which further strengthens the importance of aiming for full remission in the treatment of depression.

Adult↗
PubMed2005

The cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke: results from the Study on COgnition and Prognosis in the Elderly.

Patients who survive a first stroke are often left with permanent disabilities, and have significant needs for rehabilitation and long-term care. Antihypertensive treatment reduces the risk of cardiovascular events such as stroke. The purpose of this study was to investigate the cost-effectiveness of candesartan-based antihypertensive treatment for the prevention of nonfatal stroke. The cost-effectiveness analysis was based on data from Study on COgnition and Prognosis in the Elderly (SCOPE), where patients were randomly assigned to receive the angiotensin receptor blocker candesartan or placebo, with open-label active antihypertensive treatment added as needed. The analysis was carried out using a Markov model, which combined clinical and resource utilization data from SCOPE with Swedish retail prices for drugs and unit costs for in-patient stays, and outpatient visits. The cost per patient was 1949 EUR in the candesartan group and 1578 EUR in the control group. The largest share of the cost was attributed to antihypertensive treatment in the candesartan group and to the long-term cost of stroke in the control group. Candesartan-based antihypertensive treatment was associated with 0.0289 additional quality-adjusted life-years (QALYs) per patient and an incremental cost per QALY gained of approximately 13,000 EUR. Sensitivity analyses showed that these results were fairly stable. In conclusion, the cost per QALY gained with candesartan-based antihypertensive treatment lies within the range of society's willingness to pay for health gains. The results indicate that candesartan-based antihypertensive treatment is cost-effective for the prevention of nonfatal stroke.

Aged↗
PubMed2005

Expression of oestrogen receptor alpha and beta is higher in skeletal muscle of highly endurance-trained than of moderately active men.

AIM: Two known oestrogen receptors (ERs), ERalpha and the recently cloned ERbeta, are expressed in the human skeletal muscle of both males and females. The effects of oestrogen and the role of ERs in skeletal muscle tissue are not well known. Oestrogen receptors and some of their target genes are involved in angiogenic processes. It was hypothesized that ERs are expressed at a higher level in a group with higher oxidative capacity, and that such an enhanced expression would parallel expression of the angiogenic factor -- vascular endothelial growth factor (VEGF). METHOD: Muscle biopsies were taken from vastus lateralis in 10 highly endurance-trained males and 10 moderately active males and analysed for the expression of ERs and VEGF. RESULTS: The major findings in the present study were the higher mRNA levels of ERalpha, ERbeta and VEGF in the highly endurance-trained than in the moderately active group. CONCLUSION: These data suggest that the greater mRNA expression of ERalpha and ERbeta and the oestrogen-associated angiogenic factor VEGF support the hypothesis of an involvement of ERs in the adaptation of skeletal muscle to endurance training.

Adolescent↗
PubMed2003

Oestrogen receptor beta is expressed in adult human skeletal muscle both at the mRNA and protein level.

AIM: There are two known oestrogen receptors (ER), oestrogen receptor alpha (ERalpha) and the recently cloned oestrogen receptor beta (ERbeta). ERalpha mRNA has been detected in mouse, rat, bovine and human skeletal muscle. ERbeta mRNA has been detected in bovine skeletal muscle. To our knowledge, no study has investigated the expression of oestrogen receptor beta in human skeletal muscle. Therefore, the primary aim of the present investigation was to study ERbeta mRNA and protein expression in human skeletal muscle. In addition the ERalpha expression was also studied. METHODS: Muscle biopsies were taken from vastus lateralis in six healthy adults (three women and three men). mRNA expression was detected with real-time PCR (TaqMan) and protein localization by immunohistochemistry. RESULTS: A clear expression of ERalpha and ERbeta mRNA was seen in skeletal muscle in all subjects. The ERalpha mRNA expression was 180 fold higher compared with that of ERbeta mRNA. Immunohistochemistry demonstrated positive staining for ERbeta, but not for ERalpha, with localization to the nuclei of skeletal muscle fibres. On average, 70% of all nuclei were ERbeta-positive. CONCLUSION: The present study shows for the first time ERbeta mRNA and protein expression in human skeletal muscle tissue in both males and females.

Adult↗
PubMed2003

Adaptive control of the nitrate level in an activated sludge process.

In an activated sludge process for nitrogen removal, nitrate may be reduced to nitrogen gas by facultative heterotrophic bacteria in an anoxic environment. In order to guarantee sufficient supplies of readily biodegradable carbon compounds, an external carbon source often needs to be added. In this paper, an automatic control strategy for controlling the nitrate level using an external carbon source is presented. The external carbon source is added in the first anoxic zone to control the nitrate concentration in the last anoxic zone. Key process parameters are estimated on-line for a simplified Activated Sludge Model No 1. The estimated parameters are used for updating a linear quadratic controller. The strategy is illustrated in a simulation study with realistic influent data and is shown to perform very well.

Bioreactors↗
PubMed2001

Cost effectiveness of bisoprolol in the treatment of chronic congestive heart failure in Sweden: analysis using data from the Cardiac Insufficiency Bisoprolol Study II trial.

OBJECTIVE: To investigate the cost effectiveness of adding the beta-blocker bisoprolol to standard treatment in patients with congestive heart failure (CHF). DESIGN AND SETTING: A cost-effectiveness study was based on the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), a randomised clinical trial investigating the efficacy of adding bisoprolol to standard therapy of CHF. The cost-effectiveness analysis was carried out from a societal perspective. METHODS: Health effects were measured in terms of years of life gained. On the cost side, treatment costs for pharmaceuticals and hospitalisations were included. Data on healthcare resource consumption from CIBIS-II were used and were combined with average Swedish retail prices for medicines, and average costs for hospitalisations based on hospital admissions, in the base case. The costs of added years of life, i.e. consumption net of production during life-years gained were also included. RESULTS: If costs of added years of life were not included, then bisoprolol therapy increased life expectancy at an incremental cost of Swedish kronor (SEK) 13 094 (1999 values) per year of life gained. If costs of added years of life were included, then the incremental cost-effectiveness ratio of bisoprolol therapy was SEK 168 858 per year of life gained. CONCLUSIONS: For patients with CHF with the characteristics of those in CIBIS-II, the cost effectiveness of bisoprolol therapy compares favourably with that of other cardiovascular therapies.

Aged↗
PubMed2000

Proliferation and apoptosis in the evolution of endemic and acquired immunodeficiency syndrome-related Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a multifocal lesion that occurs predominantly in the skin, most frequently in people infected with HIV-1, and that evolves through early stages (patch and plaque) to a tumor-like late stage (nodular). Both, endemic African (EKS) and AIDS-associated (AKS) KS expressed human herpesvirus 8 (HHV-8) as shown by PCR. By immunohistochemistry the expression of cellular Bcl-2 and c-myc was confined in early stages of both EKS and AKS to relatively few endothelial cells (EC) whereas in nodular KS most of spindle cells (SC) strongly expressed both genes. CD40 was usually strongly expressed in SC at all KS stages as well as in EC of non-involved tissue whereas CD40L (CD154) was not demonstrable. Fas (CD95) was moderately to weakly expressed by SC whereas p53 and Waf-1 were found in less than 5% of the SC. In both AKS and EKS at nodular stage almost no apoptotic SC were detected. In most AKS and EKS low levels of cell proliferation were seen but AKS showed consistently higher values compared to EKS. All clinical types and stages of KS showed a diploid cellular DNA content by flow cytometric analysis of microselected lesions. Thus, we conclude that KS during evolution represents diploid, probably reactive, cell proliferation, which progressively increases the expression of strong cellular and also viral (HHV-8) antiapoptotic factors.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Recruitment of monocyte derived dendritic cells ex vivo from SIV infected and non-infected cynomolgus monkeys.

This study shows that characteristic dendritic, antigen presenting cells, can be generated from adherent peripheral blood mononuclear cells (PBMC)/monocytes of uninfected and SIVsm-infected cynomolgus monkeys after stimulation in vitro with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4. The recruitment of monocyte derived dendritic cells (MDDC) was usually possible irrespective of the level of immunodeficiency (CD4-level) and viremia. The cynomolgus MDDC closely resembled their human counterpart (immature MDDC) with regard to capacity to upregulate CD1a, CD40, CD86 and human leukocyte antigen (HLA)-DR and develop dendrites and veiled processes. Such MDDC also increased their capacity for antigen uptake (dextran endocytoses/macropinocytosis) and for induction of T-cell proliferation in mixed leukocyte reaction (MLR) assays. However, although no clear difference with regard to phenotype and morphology was seen between MDDC from SIV-infected and uninfected monkeys, a reduction in MLR responsiveness in MDDC from SIV infected monkeys was consistently detected within each experiment.

Animals↗
PubMed2000

Body composition and muscle constituents during weight loss: studies in obese patients following gastroplasty.

BACKGROUND: The influence of rapid and prolonged weight loss on body composition and muscle constituents in the obese patient is not well known. There are serious complications related to rapid and prolonged weight loss. It is of general interest to increase the understanding of the mechanisms and consequences of significant weight loss in man. METHODS: In 40 obese patients, the body composition and muscle constituents were studied before and during 1 year of weight loss following gastroplasty. The study was undertaken in two groups (A and B) of obese patients, comprising 32 women and eight men, body weight 82-175 kg and aged 24-49 years. Mean BMI in group A and B was 45 (W/H(2)) and 43 (W/H(2)) respectively. Body composition was assessed by total body potassium measurements and muscle constituents were determined by analyses of muscle specimens obtained percutaneously. RESULTS: The preoperative body composition was found to be equal parts of lean body mass and body fat. Preoperatively, muscle constituents revealed a higher protein content per cell and a lower potassium concentration related to fat-free solids. The loss of 18-28% body fat and lean body mass occurred in equal proportions during the first 3 postoperative months of rapid weight loss, followed by a continuous decrease of body fat but not of lean body mass. The concentrations of proteins and potassium per muscle cell revealed a reduction during the period of rapid weight loss. The RNA/DNA ratio 1 year after surgery was still reduced, indicating a low protein synthesis rate. CONCLUSIONS: Preoperatively mean body fat accounted for 50% of the body weight in obese patients. Following weight loss, body fat, lean body mass and concentrations of proteins were reduced compared to preoperative values. After the period of rapid weight loss, with reduction of lean body mass and body fat in parallel, a progressive reduction of body fat was observed whereas the lean body mass did not decrease further. Protein synthesis rate was still low 12 months after surgery.

Adult↗
PubMed1999

Proliferation and apoptosis-related gene expression in experimental acquired immunodeficiency syndrome-related simian lymphoma.

Lymphomas in 10 cynomolgus monkeys infected with a simian immunodeficiency virus (SIVsm) were studied with regard to proliferative activity and apoptosis-related gene expression. All were diffuse large-cell lymphomas, showed mono or oligoclonality and a 9/10 diploid cellular DNA content. Expression of a simian homologue to Epstein-Barr virus (HVMF-1) was shown in nine cases. The lymphomas showed moderate to high proliferative activity by Ki67 immunostaining and DNA flow cytometry, and a low number of apoptotic cells detected by TdT-mediated dUTP nick-end labeling (TUNEL). Immunohistochemistry showed abundant tumor infiltrating TIA-1(+) cytotoxic lymphocytes (CTL) and macrophages. Bcl-2, Mcl-1, and also Bax and Bak, but not p53 were demonstrable in the tumor cells by immunostaining. Our findings suggest a causal relationship between HVMF-1 infection and a low apoptotic index of the lymphomas due to the expression of Bcl-2. The apparent inefficient function of tumor-infiltrating CTL could be due to inactivation of CTL and/or resistance of the lymphoma cells to CTL effects. The tumors showed immunoreactivity for CD18, CD29, and CD49d, but not for CD11a, mimicking the phenotype of human Epstein-Barr virus (EBV)-related lymphomas. In summary, our observations indicate a high similarity between this simian model of acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARL) and human ARL and other immunosuppression-related lymphomas.

Animals↗
PubMed1999

Epstein-Barr virus expression in Hodgkin's disease in relation to patient characteristics, serum factors and blood lymphocyte function.

Epstein-Barr virus (EBV) expression was investigated by immunohistochemistry (latent membrane protein 1 [LMP-1]) and in situ hybridization (EBV encoded RNA [EBER]) in biopsies from 95 patients with untreated Hodgkin's disease (HD). Tumour EBV status was related to EBV antibody titres, spontaneous and concanavalin A induced blood lymphocyte DNA synthesis, serum levels of soluble (s) CD4, sCD8, sCD25, sCD30, sCD54, beta2-microglobulin, thymidine-kinase, routine chemistry, patient characteristics, complete remission and survival. The median follow-up time was 145 months (range 60-257). Tumour EBV-positive (n = 30; 33%) and negative (n = 62; 67%) patients did not differ with regard to sex, age, stage, presence of bulky disease or B-symptoms, remission rate or survival. The proportion of EBV+ cases was significantly higher among patients with mixed cellularity histopathology (58%) as compared to the nodular sclerosis subtype (18%; P < 0.001). The total white blood cell (WBC) counts were significantly lower in EBV+ patients (P < 0.01), who also had significantly higher levels of sCD54 (P < 0.02) and a tendency towards lower levels of sCD30 (P = 0.056). Patients in the tumour EBV+ group had significantly higher IgG antibody titres to restricted early antigen (EA-R) (P < 0.02). Hence, clinical features and outcome were not related to tumour EBV status. However, HD patients with EBV+ tumours had elevated sCD54 levels, higher antibody titres to EA-R and decreased total WBC counts. A potential causal relationship between EBV tumour status and these findings needs to be further explored.

Adult↗
PubMed1999

Noise reduction of renograms: a new algorithm applied to simulated renograms for evaluation of the renal retention function.

Physiological information about an organ may be assessed from the retention function as derived by deconvolution analysis. However, noise in data may cause distortion of the retention curve and potentially induce methodological errors. To take full advantage of all parts of the retention function, i.e. even the vascular part, we have developed a non-linear noise reduction algorithm. The algorithm is an adaptive polynomial fit (APF) in a sliding segment over the renogram to be deconvoluted. Each segment is modelled by the lowest polynomial resulting in a root of mean square error lower than a pre-set value. APF was tested in comparison with conventional repetitive 1:2:1 smoothing and rectangular window smoothing, using a set of simulated retention functions and corresponding renograms with superimposed artificial noise. The outcome was evaluated by comparing the generated retention functions with the simulated ones. The conventional smoothing algorithms, as well as APF, induced some distortion of the retention function, but the deviation from the true retention function is essentially lower in the case of APF. In addition, APF seems to be more robust in cases of essentially reduced renal function and thereby relative high noise levels. APF reduces noise in data, leading to retention functions with reliable information in terms of a tracer's first passage, uptake and outflow.

Algorithms↗
PubMed1999

Tolerance induction using the Malmö treatment model 1982-1995.

The ultimate goal in the treatment of haemophilia patients with inhibitors is to eradicate permanently the inhibitor and induce tolerance. Here we summarize our experience at the Malmö centre regarding tolerance induction according to the Malmö Treatment Model. The protocol includes immunoadsorption if needed, neutralization of inhibitor and replacement with factor concentrates, cyclophosphamide intravenously for 2 days (12-15 mg kg-1 bw) and then orally (2-3 mg kg-1 bw) for an additional 8-10 days and intravenous gammaglobulin daily at dosages of 0.4 g kg-1 bw for 5 days. This protocol has been applied in 23 haemophilia patients with inhibitors, 16 haemophilia A patients and seven haemophilia B patients. Altogether 36 attempts have been made to induce tolerance. Ten of the 16 haemophilia A (62.5%) and 6/7 patients with haemophilia B (86%) became tolerant after the treatment. The chances of success or failure are roughly equal, if the series is considered in a historical perspective. The data showed that the chances of success in tolerance induction with the Malmö protocol were best in those patients with low inhibitor titres, with relatively low historical inhibitory peak and with a long interval since the previous replacement therapy. This was especially true where no inflammatory state was present at the start or during tolerance induction. The advantage with this method compared to the high-dose regimen is that in the successful cases tolerance can be achieved within 3-4 weeks.

Adolescent↗