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Objective: We aimed to describe the progression rate into manifest aortic stenosis (AS) in subjects with normal aortic valves or in an early phase of calcific aortic valve disease.Methods: Participants were recruited from the Tromsø Study, a population-based health survey. In our prospective cohort study, we performed two echocardiographical examinations (2001 and 2008) of a random sample of 1884 participants. AS was defined as a mean aortic valve gradient ≥15 mm Hg or a peak flow exceeding 2.6 m/s. Those with lesser values were stratified into three groups based on mean gradients (cut-off 5 and 10 mm Hg) and peak aortic flow (cut-off 1.5 and 2 m/s).Results: At baseline, 71 participants had gradients from 10 to 14.9 mm Hg, of whom 32.4% developed AS during follow-up. AS developed in only 3.6% of those with a baseline gradient of 5-9.9 mm Hg and in 0.3% of those with a gradient <5 mm Hg. Almost identical separations were obtained among the three flow velocity groups. Of the 45 subjects who developed incident AS, 56% acquired mild, 33% moderate and 11% severe AS. Their mean gradient progression rate was 2.7 mm Hg/year.Conclusions: The results support that subjects with a mean aortic valve gradient of 10-15 mm Hg or aortic flow >2.0 m/s should be followed routinely. This group identifies about half of those who develop AS in the following 7 years. [ABSTRACT FROM AUTHOR]

To disclose risk factors of incident aortic stenosis (AS) and progression of established AS. A prospective cohort study. The Tromsø Study, a population based health survey. Over a 14 years span we performed three repeated echocardiographic examinations (1994, 2001 and 2008) of a random sample of initially 3,243 participants. Data from the only hospital serving this population were included in the follow up. Throughout the study 132 participants were diagnosed with incident AS, defined as mean aortic valve gradient ≥15 mmHg. Cox proportional hazards regression disclosed age (HR 1.11, 95 %CI 1.08-1.14), systolic blood pressure (BP) (HR 1.01, 95 % CI 1.00-1.02), active smoking (HR 1.71, 95 % CI 1.09-2.67), and waist circumference (HR 1.02, 95 % CI 1.00-1.03) as independent predictors of incident AS. Analysis of risk factors for progression of AS disclosed a higher mean aortic gradient at first measurement ( p = 0.015), weight ( p = 0.015), a low haemoglobin (Hgb) ( p = 0.030) and high density lipoprotein (HDL) ( p = 0.032) as significant independent predictors. Age, systolic BP, smoking and waist circumference were independent predictors of incident AS, whereas cholesterol was not. Mean aortic gradient at first measurement, weight, an elevated HDL and low Hgb increase the progression rate of the disease. Our data indicate that calcific aortic valve disease is a distinct pathophysiological process, with age, smoking and 'wear and tear' of the valve being major contributors to the disease development. [ABSTRACT FROM AUTHOR]

This paper describes the concept of parallel electromembrane extraction (Pa-EME) with flat membranes in a multiwell format for the first time. The setup is based on a multiwell plate and provided simultaneous and selective isolation, cleanup, and enrichment of several human plasma samples as well as LC-MS-compatible extracts within 8 min of extraction. Undiluted human plasma samples spiked with four antidepressant drugs were added to separate wells in the donor plate. Subsequently, the samples were extracted with Pa-EME. The four drugs migrated electrokinetically from undiluted human plasma through a flat polypropylene membrane impregnated with 2-nitrophenyl octyl ether, and were isolated into formic acid. Extraction time, extraction voltage, agitation rate, sample volume, and acceptor solution volume were all optimized with an experimental design. The optimal conditions were as follows: The agitation rate was 1,040 rpm, and an extraction voltage of 200 V was applied. The sample volume and acceptor solution volume was 240 and 70 μL, respectively. The extraction was continued for 8 min. Eventually, the extracts were analyzed by LC-MS/MS. The combination of Pa-EME with LC-MS/MS provided quantitation limits below the therapeutic level and reported relative standard deviations in the range 5-13 %. Linear calibration curves were obtained for all analytes, and the correlation coefficients were above 0.9974 in the range 1-400 ng mL. The drug concentrations from two subjects treated with quetiapine and sertraline were successfully determined with Pa-EME combined with LC-MS/MS. Post-column infusion experiments demonstrated that Pa-EME provided extracts free from interfering matrix components. [ABSTRACT FROM AUTHOR]

Objective: To assess prevalence, incidence, prognosis and progression of degenerative valvular aortic stenosis (AS). Setting: The Tromsø Study and the University Hospital of North Norway. Design: Population based prospective study. Population: Over a 14 year span we performed three repeated echocardiographic examinations (1994, 2001 and 2008) of a random sample of initially 3273 participants. Data from the only hospital serving this population were included. Results: There were 164 subjects with AS. Prevalence consistently increased with age, average values being 0.2% in the 50-59 year cohort, 1.3% in the 60-69 year cohort, 3.9% in the 70-79 year cohort and 9.8% in the 80-89 year cohort. The incidence rate in the study was 4.9‰/year. The mean annual increase in mean transvalvular pressure gradient was 3.2 mm Hg. The increase was lower in mild AS than in more severe disease, disclosing a non-linear development of the gradient, but with large individual variations. Mortality was not significantly increased in the asymptomatic AS-group (HR=1.28), nor in those who received aortic valve replacement (n=34, HR=0.93), compared with the general population. Conclusion: This is the first study to document the incidence and prognosis of AS in a general population with surgery as a treatment option. It reveals an accelerated progression of the aortic mean gradient as the disease advances. The prognosis of AS seems to be comparable with the normal population in the asymptomatic stage and after successful surgery, indicating that the follow-up and timing of surgery has been adequate for this patient group. [ABSTRACT FROM AUTHOR]

In this instalment of "Sample Preparation Perspectives," Norwegian authors from the University of Oslo describe the practical aspects of hollow fibre liquid-phase microextraction in the three-phase mode (HF3LPME). The guest authors highlight important practical issues related to the supported liquid membrane, the hollow fibre and the extraction itself. They also discuss practical work with electromembrane extraction (EME), which is related to HF3LPME but uses an electrical potential as the driving force for the extraction. [ABSTRACT FROM AUTHOR]

Context: Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.Objective: To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.Design, Setting, and Participants: Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.Interventions: Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721).Main Outcome Measures: Cancer incidence, cancer mortality, and all-cause mortality.Results: During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B(12) vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B(12) vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B(12) vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12). Vitamin B(6) treatment was not associated with any significant effects.Conclusion: Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.Trial Registration: clinicaltrials.gov Identifier: NCT00671346. [ABSTRACT FROM AUTHOR]

The article offers information on a study which investigated the effects of treatment with B vitamins on cancer outcomes and all-cause mortality. A total of 6837 patients were recruited to participate in two randomized, double-blind, placebo-controlled clinical trials conducted in Norway between 1998 and 2005, and followed up through December 31, 2007. Treatment interventions included oral treatment with folic acid combined with vitamin B12 and vitamin 6, folic acid combined with vitamin B12, vitamin 6 alone and placebo. Presented in details are the research findings.

The present work describes the first systematic study of electromembrane extraction (EME) from biological matrices under physiological conditions. Six basic drugs with protein binding in the range of 20–97% were extracted from untreated human plasma and whole blood through a supported liquid membrane (SLM) consisting of 1-ethyl-2-nitrobenzene impregnated in the walls of a hollow fiber, and into an acidified aqueous solution inside the lumen of the fiber. The electrical potential difference over the membrane reduced the protein binding of the drugs and transported the free drug fraction over the membrane. Recoveries in the range 25–65% were obtained with 10-min extraction time and an applied voltage of only 10 V over the SLM. Interday precision better than 20% RSD and linearity in the range 0.5–10 µg/mL were obtained for nortriptyline and methadone. Extraction from untreated whole blood was also demonstrated with recoveries in the range 19–51%. [ABSTRACT FROM AUTHOR]

Background: In order to maintain both quality and efficiency of health services in a small country with a scattered population, Norway established a monopoly system for 38 highly specialized medical services. The geographical distributions of these services, which are provided by one or two university hospitals only, were analysed. Methods: The counties of residence for 2 711 patients admitted for the first time in 2001 to these 31 monopolies and 7 duopolies were identified. Results: The general tendency observed was that with increasing distance from residential home to monopoly hospitals there was a declining coverage of these health services. The same pattern was found even with regard to explicit diagnoses or treatments such as organ transplantations (except renal transplantations). Duopolies seemed to yield a more even geographical distribution of the services. Conclusion: Monopolies may serve as a useful means for maintaining quality in highly specialized medical services, but seem to have an inherent tendency to do this at the expense of geographical equality. [ABSTRACT FROM AUTHOR]

Aims: To assess left ventricular function by conventional and pulsed wave tissue Doppler (PWTD) echocardiography in subjects with mild secondary hyperparathyroidism, and to evaluate whether PWTD would be more sensitive than conventional echocardiography in detecting subtle changes in LV systolic and diastolic function. Methods: In the fifth Tromsø study (2001) serum PTH and calcium were measured in 7,954 subjects. One hundred subjects with secondary hyperparathyroidism (SHPT; serum PTH >6.40 pmol/l and serum calcium <2.40 mmol/l) and 106 control subjects with normal PTH and calcium levels and with no history of cardiovascular disease were examined at the follow-up 6–12 months later. Results: Conventional transthoracic echocardiography and PWTD of mitral annulus were successfully performed in 83 cases and 88 controls. At follow-up mean serum PTH values were 6.0 ± 2.2 versus 3.2 ± 1.3 pmol/l (p < 0.05) and mean calcium 2.28 ± 0.10 versus 2.33 ± 0.08 mmol/l (p < 0.05) in cases and controls, respectively. Unpaired t test and multiple linear regression analyses were used. No significant differences in conventional echocardiographic parameters were found. However, PWTD showed reduced systolic velocity in septal, lateral and anterior mitral annulus (p < 0.05) and also reduced early diastolic velocity in septal and anterior mitral annulus (p < 0.05). Conclusion: Subjects with mild SHPT have impaired left ventricular long axis function as evaluated by PWTD compared to conventional echocardiography. PWTD seems to be a more sensitive tool in detecting minor changes in left ventricular function and the new modality should routinely be included in studies evaluating left ventricular function, especially the long axis function. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To search for cardiac abnormalities in systemic lupus erythematosus (SLE).Methods: 35 patients examined by 2-D transthoracal Doppler and transesophageal echocardiography.Results: Mitral and aortic valve abnormalities were seen in 12 patients (34%) respectively, and occurred altogether in 16 patients (46%). They were in general significantly associated with longer disease duration, but not with anticardiolipin antibodies (aCL), disease activity, or any other variable, except for time on corticosteroids. which was significantly longer in patients with aortic valve calcifications.Conclusion: Valve masses and valve thickening--often in combination--are the most frequent structural findings in SLE, occurring more often on the aortic than on the mitral valves. Factors other than antiphospholipid antibodies, medication, hypertension, or coronary heart disease seem to be responsible for this phenomenon. Drugs that modulate inflammation in endo- and pericardial tissue may, at least in part, be responsible for the observed mitral valve calcifications and pericardial fibrosis. [ABSTRACT FROM AUTHOR]

On the basis of a questionnaire in a population study in the county of Nordland, Norway, the prevalence of palpitations and its associations to some lifestyle factors, depression and self-rated health were analysed. All the 10,497 residents aged 40 to 42 years were invited to participate, 82% attended, 87% of the attenders returned a questionnaire by mail, and 6436 subjects were included in this report. The prevalence of palpitations was 15% in men and 25% in women. Palpitations were significantly associated with coffee consumption, smoking, alcohol intoxication, physical inactivity, depression and poor self-rated health in the univariate analyses. In a logistic regression analysis, the relations between palpitations and lifestyle were weakened. Significant predictors for palpitations were depression and poor self-rated health in both sexes, in addition to heavy coffee drinking and physical inactivity in men and alcohol intoxication in women. In conclusion, palpitations were more firmly linked to depression and self-evaluated health than to lifestyle. [ABSTRACT FROM PUBLISHER]