Biomedical subjects

F Larsen

Publications and source records attributed to F Larsen.

At least 19 recordsLinked to original sources

PubMed2006

Mannose-binding lectin and its genetic variants.

Mannose-binding lectin (MBL) is a collagen-like serum protein that mediates activation of the complement system and is of importance for host defence. Common variant alleles situated both in the promoter and structural region of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variation in MBL serum concentration influences the susceptibility to and the course of different types of infections, autoimmune, metabolic and cardiovascular diseases, but this is still a subject of debate. The fact that these genetic variations are very frequent indicates a dual role for MBL in host defence. In this survey, we summarize the current molecular understanding of human MBL genetics.

Alleles↗

PubMed2005

The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects.

The pharmacokinetics of escitalopram (S-citalopram) and its principal metabolite, S-demethylcitalopram (S-DCT), were investigated after intravenous and oral administration to healthy subjects. After intravenous infusion of escitalopram, the mean systemic clearance and volume of distribution were 31 L/h and 1,100 L, respectively. After oral administration of single or multiple doses, the absorption was relatively fast, with the maximum observed plasma or serum concentration (C(max)) attained after 3 to 4 hours. The mean half-lives were 27 and 33 hours, respectively; steady state was attained within 10 days. The area under the plasma or serum concentration time curve from time zero to 24 hours and C(max) was both linear and proportional to the dose. The apparent volume of distribution was around 20 L/kg. Comparison of the systemic and oral clearance implied a high absolute bioavailability. There was no evidence of interconversion from S-citalopram to R-citalopram either in plasma or in urine. Concurrent intake of food had no effect on the pharmacokinetics of escitalopram or its metabolite. All treatments were well tolerated.

Administration, Oral↗

PubMed2003

Lung perfusion scintigraphy prior to lung volume reduction surgery.

PURPOSE: The aim of this study was to evaluate whether lung perfusion scintigraphy (LPS) contributes to the preoperative classification of emphysema heterogeneity in patients undergoing LVRS (lung volume reduction surgery) compared to classification based only on computed tomography (CT). MATERIAL AND METHODS: Forty-five potential candidates for LVRS were examined with CT and LPS. The distribution of emphysema within the lungs was visually classified into three categories: markedly heterogeneous, intermediately heterogeneous, or homogeneous. The results of the two imaging techniques were compared to an objective, CT-based computerized classification of heterogeneity. RESULTS: Visual evaluation of all 90 lungs resulted in 50 correct classifications based on CT, in 40 based on LPS and in 68 correct classifications based on the combination of CT and LPS. The combination was superior to CT alone (p<0.01) in classification of emphysema heterogeneity. There was no significant difference between the evaluations based on either CT or LPS. CONCLUSION: The combined information from CT and LPS are superior in assessing emphysema heterogeneity prior to LVRS.

Female↗

PubMed2003

Implementing telemedicine services in northern Norway: barriers and facilitators.

Telemedicine is not simply a technology - it also involves processes. The use of telemedicine is influenced by many factors. Our intention was to examine what conditions promote the use of telemedicine between general practitioners (GPs) and hospitals. Qualitative interviews were undertaken with 16 GPs in northern Norway. The extent to which GPs were using the services was limited, although some used them fairly frequently. The most widely used service was teledermatology. The GPs saw advantages of the services in general and saw clear benefits for their patients. The services were considered to be time-consuming, and the lack of adequate government remuneration for the time involved in teleconsultations was seen as a barrier to their use. The GPs focused on their own ability to handle new technology and expressed a need to practise more.

Attitude of Health Personnel↗

PubMed2001

Pyrite oxidation in unsaturated aquifer sediments. Reaction stoichiometry and rate of oxidation.

The oxidation of pyrite (FeS2) contained in unsaturated aquifer sediment was studied by sediment incubation in gas impermeable polymer laminate bags. Reaction progress was followed over a period of nearly 2 months by monitoring the gas composition within the laminate bag. The gas phase in the incubation bags became depleted in O2 and enriched in CO2 and N2 and was interpreted as due to pyrite oxidation in combination with calcite dissolution. Sediment incubation provides a new method to estimate low rates of pyrite oxidation in unsaturated zone aquifer sediments. Oxidation rates of up to 9.4 x 10(-10) mol FeS2/g x s are measured, and the rates are only weakly correlated with the sediment pyrite content. The reactivity of pyrite, including the inhibition by FeOOH layers formed on its surface, apparently has a major effect on the rate of oxidation. The code PHREEQC 2.0 was used to calculate the reaction stoichiometry and partitioning of gases between the solution and the gas phase. Pyrite oxidation with concurrent calcite dissolution was found to be consistent with the experimental data while organic carbon oxidation was not. The reaction involves changes in the total volume of the gas phase. The reaction scheme predicts the volume of O2 gas consumed to be larger than of CO2 produced. In addition the solubility of CO2 in water is about 30 times larger than of O2 causing a further decrease in total gas volume. The change in total gas volume therefore also depends on the gas/water volume ratio and the lower the ratio the more pronounced the loss of volume will be. Under field conditions the change in total volume may amount up to 20% in the absence of calcite and over 10% in the presence of calcite. Such changes in gas volume during the oxidation of pyrite are expected to result in pressure gradients causing advective transport of gaseous oxygen.

Carbon Dioxide↗

PubMed2001

Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit.

BACKGROUND & AIMS: This study was designed to characterize [D-F(5)Phe(6)D-Ala(11)]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5-500 microg. kg(-1). h(-1)) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. METHODS: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. RESULTS: Intravenous BIM26226 potently inhibited gastric lag time (114 +/- 7 vs. 41 +/- 6 minutes [control]) and gastric emptying rate (0.11 +/- 0.02%/min vs. 0.26 +/- 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 +/- 41 vs. 262 +/- 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t(50%), 35 +/- 4 minutes), which BIM26226 inhibited significantly (t(50%), 64 +/- 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. CONCLUSIONS: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.

Adult↗

PubMed2001

Lack of effect of citalopram on the steady-state pharmacokinetics of carbamazepine in healthy male subjects.

Carbamazepine, a drug used in the treatment of seizure disorders, and citalopram, a highly selective serotonin reuptake inhibitor used for the treatment of depression and other psychiatric disorders, are both metabolized predominantly by the cytochrome P4503A4 isozyme. In this study, the effect of subchronic administration of citalopram on the steady-state pharmacokinetics of carbamazepine was evaluated in 12 healthy male subjects. Carbamazepine was administered orally twice daily as a 100-mg dose from days 1 to 3, as a 200-mg dose twice a day from days 4 to 6, and as a 400-mg dose once a day from days 7 to 35. Citalopram, 40 mg, administered once daily, was added to the carbamazepine-dosing regimen on days 22 to 35. The steady-state plasma concentration profiles of carbamazepine and its active metabolite, carbamazepine 10,11-epoxide, on day 35 (in the presence of steady-state levels of citalopram) were compared to the corresponding carbamazepine and epoxide metabolite profiles on day 21 (in the absence of citalopram). No significant differences were found between mean steady-state values for maximal drug concentration, area under the curve, or time of maximal concentration values for carbamazepine and its epoxide metabolite before and after the addition of citalopram to the daily carbamazepine dosing regimen (p > 0.05). These results suggest that the use of citalopram in patients stabilized on carbamazepine should not produce clinically significant changes in carbamazepine plasma concentrations.

Adolescent↗

PubMed2001

Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist.

BACKGROUND AND AIMS: The main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to determine if endogenous GRP is a physiological regulator of gastric acid secretion and gastrin release. METHODS: Our study consisted of three parts. In part I, subjects received saline or BIM26226 followed by graded doses of intravenous human GRP in a four period crossover design. In part II, subjects received BIM26226 or saline during oral meal ingestion or modified sham feeding. In part III, subjects received an acidified meal in the presence and absence of BIM26226 in a two period crossover design. In addition, gastrin and somatostatin mRNA were measured in biopsy specimens during saline and BIM26226 infusion. RESULTS: BIM26226 dose dependently inhibited GRP induced acid output. Acid secretion after oral liquid meal intake and sham feeding was significantly inhibited by BIM26226 (p<0.01) whereas plasma gastrin release remained unchanged. Gastrin and somatostatin mRNAs were not significantly different after saline or BIM26226. CONCLUSIONS: BIM26226 is a potent GRP antagonist in humans. Endogenous GRP may be a physiological regulator of gastric acid secretion. Gastrin release does not seem to be under the control of GRP.

Adult↗

PubMed2001

Lack of citalopram effect on oral digoxin pharmacokinetics.

The effect of chronic administration of citalopram on the single oral dose pharmacokinetics of digoxin was evaluated in 11 healthy adult subjects in an open, one-way crossover study. Subjects received 1 mg digoxin on day 1. Serial blood samples and total urine were collected over 192 hours, followed by an 11-day washout period. On days 22 through 50, subjects received 40 mg citalopram once daily. On day 43, a single dose of 1 mg digoxin was coadministered; again, serial blood samples and total urine were collected over 192 hours after the digoxin dose. There were no statistically significant differences in any of the digoxin pharmacokinetic parameters (AUC(0-->24), AUC(0-->infinity), Cmax, tmax, t(1/2), CL/F, CLrenal, and Ae(0-->infinity)), and the 90% confidence intervals for treatment differences for the parameters (except for tmax) were all within 80% to 125%. Concomitant digoxin administration did not significantly affect citalopram pharmacokinetics. The treatment was well tolerated by all subjects; no serious adverse events and no clinically significant ECG changes were observed. These data suggest that it is unlikely that concomitantly administered citalopram would have any significant effect on serum digoxin concentrations in patients who are receiving chronic digoxin therapy.

Administration, Oral↗

PubMed2001

The reproducibility and sample size requirements of exercise-induced bronchoconstriction measurements.

Dry air exercise challenges are frequently used to screen medications that have potential utility in the management of exercise-induced bronchoconstriction (EIB). The purpose of this study was to determine the reproducibility of three outcome measurements made using such challenges, and sample size requirements for drug evaluation studies based on these outcomes. Forty adult subjects with asthma, who tested positively on a screening exercise challenge, were subjected to two further identical challenges, separated by 1 to >35 days. Outcome measurements included the maximum per cent fall in forced expiratory volume in one second (FEV1), after exercise (% fallmax), and the area under the per cent fall in FEV1/time curve for 30 min (AUC30) and 60 min (AUC60) after exercise. The reproducibility of these outcomes, as assessed by intraclass correlation coefficients was 0.72, 0.53 and 0.35 for % fallmax, AUC30 and AUC60 measurements, respectively. The sample size requirements to demonstrate an attenuation of EIB equivalent to a 50% reduction in % fallmax was 9, 14 and 19 subjects for the % fallmax, AUC30 and AUC60 responses, respectively (90% power). It is concluded that the maximum percentage fall in forced expiratory volume in one second has greater reproducibility and results in greater power in clinical trials than area under the curve measurements. Sample size calculation curves are provided which may be used in study design and interpretation of published studies.

Adult↗

PubMed2001

ECG-abnormalities in Japanese and Swedish patients with sarcoidosis. A comparison.

BACKGROUND AND AIM OF THE WORK: ECG abnormalities are more common in patients with sarcoidosis than in controls. The incidence of cardiac sarcoid granulomas in the Japanese population has been found to be higher than that seen in Caucasians. We compared the prevalence of ECG abnormalities in Japanese and Swedish patients with sarcoidosis. METHODS: Twelve-lead routine ECG's were compared between consecutive patients (134 Japanese and 149 Swedish) of similar age with histologically verified sarcoidosis or a high clinical probability of the disease and a history of no more than 12 months before the ECG. RESULTS: There was no statistically significant difference in the prevalence of first degree AV block, ST-T-segment abnormalities, right bundle branch block (RBBB) and left anterior block (LAH) in Japanese and Swedish patients. Among the Swedes, the results were compared with those of a smaller group (n = 29) of older patients with a longer disease course. In these few patients LAH and RBBB occurred more frequently than in patients with a recent diagnosis. CONCLUSIONS: ECG abnormalities in patients with sarcoidosis seem to be of similar frequency in Japan and Sweden. ST-T changes and first degree AV block would appear early in the course of the disease, whereas more pronounced conduction defects may appear later.

Cardiomyopathies↗

PubMed2000

Effect of citalopram on plasma levels of oral theophylline.

BACKGROUND: Citalopram and theophylline may be prescribed together to treat patients with depression and asthmatic disease. Because theophylline has a low therapeutic index, small changes in plasma levels may result in therapeutic failure or adverse effects. Both citalopram and theophylline are metabolized by cytochrome P450 (CYP) isozymes. Theophylline is metabolized by CYP1A2; however, the extent to which citalopram interacts with this isozyme in vivo is not known. OBJECTIVE: This study was conducted to investigate whether citalopram alters plasma levels of oral theophylline. METHODS: In an open-label, multiple-dose study, healthy nonsmoking volunteers 18 to 45 years of age were administered a single oral dose of theophylline (300 mg) on day 1. Beginning on day 3, citalopram 40 mg was administered daily through day 24 to achieve steady-state plasma levels. On day 23 a single oral dose of theophylline 300 mg was coadministered with citalopram 40 mg. Fasting plasma levels of theophylline were measured on day 1 (in the absence of citalopram) and on day 23 (in the presence of steady-state plasma concentrations of citalopram) periodically for 36 hours. RESULTS: Thirteen subjects (8 men and 5 women) participated; all completed the study. One subject was not included in the pharmacokinetic calculations. Citalopram treatment had no effect on the pharmacokinetic characteristics of theophylline. CONCLUSIONS: Citalopram dosing to steady state did not inhibit or induce the metabolism of theophylline in this population of healthy volunteers. Dose adjustment of theophylline thus may not be necessary in patients receiving concurrent therapy with citalopram.

Administration, Oral↗

PubMed2000

Linkage analysis of a candidate region in Scandinavian sib pairs with multiple sclerosis reveals linkage to chromosome 17q.

To date, four genome screens have been completed in the demyelinating autoimmune disease multiple sclerosis (MS). Although these screens failed to identify any loci with major effects on susceptibility, several novel regions of potential linkage were suggested, including the long arm of chromosome 17. In order to further pursue this promising region we have investigated six highly polymorphic microsatellite markers in 115 Scandinavian families with MS affected sib pairs. Multipoint linkage analysis revealed a peak maximum likelihood score (MLS) of 0.9 in the region of marker D17S787. Stratifying the results on the basis of HLA-DR2 status showed that the linkage was not limited to families segregating for the HLA-DR2 allele as has previously been suggested. In conclusion, our results further support the proposal that a multiple sclerosis susceptibility locus is contained on chromosome 17q.

Chromosomes, Human, Pair 17↗

PubMed1999

Dose-dependent gastrointestinal effects of the somatostatin analog lanreotide in healthy volunteers.

OBJECTIVE: To investigate the gastrointestinal effects of intravenous lanreotide. METHODS: Twenty healthy male subjects participated in 2 subsequent placebo-controlled, double-blind crossover studies. The effects of 3 doses of lanreotide (50, 100, and 200 microg/h) were investigated on 24-hour intragastric acidity (study I), food-stimulated gallbladder contraction, and plasma cholecystokinin release (study II). RESULTS: Lanreotide showed linear pharmacokinetics. It raised median intragastric pH significantly and in a dose-dependent manner: from 1.4+/-0.2 (placebo) to 2.5+/-0.8 (P < .002) during administration of 50 microg/h lanreotide, to 3.2+/-0.7 (P < .001) during 100 microg/h lanreotide, and to 4.3+/-0.7 (P < .001) during 200 microg/h lanreotide. However, no significant inhibition of gastrin secretion could be established. All doses completely inhibited postprandial gallbladder contraction. CONCLUSION: Intravenous administration of lanreotide at rates applied in this study was able to significantly inhibit intragastric acid secretion and postprandial gallbladder contraction; under these conditions few untoward effects were noted.

Adult↗

PubMed1999

The impact of pleurodesis in malignant effusion on respiratory function.

Pleurodesis of malignant pleural effusion provides for a substantially better quality of life compared to onging exudation with the need for repeated evacuation of fluid. Successful pleurodesis leads to permanent cessation of fluid production as a result of the formation of fibrous adhesion between the lung and costal pleura which in theory, however, might restrict lung mobility. In patients with poor lung function, or with need for bilateral pleurodesis, the apprehension of further impairment of lung function often arises. The aim of this study was to evaluate the effects of pleurodesis on lung function. Therefore 10 patients with malignant pleurisy with very limited tumour were investigated. They were without radiological signs of tumour infiltration in the lung parenchyma, without visible tumour growth in the pleural space during thoracoscopy and had undergone a successful one-sided pleurodesis. Respiratory function tests were performed at different times, 1-102 months after pleurodesis. The assessment consisted of: static and dynamic spirometry, exercise testing with blood gas determination and radiospirometry. Spirometric values were slightly low, but in general within the reference limits. Blood gas determination showed no signs of alveolar hypoventilation. Radiospirometry showed a slight attenuation of activity in the treated lung but similar turnover of gas of the treated vs. the untreated side. The study showed that pleurodesis in malignant pleurisy has only minor impact on respiratory function.

Adult↗

PubMed1999

Peri-operative acute phase response and cytokine releasein women with breast cancer: modulation bypolyadenylic-polyuridylic acid.

AIMS: Acute phase reactants (APRs) are believed to play an important biological role in trauma, sepsis and malignant disease. We have investigated the induction of the APR, C-reactive protein (CRP), by the biological response modifier, polyadenylic-polyuridylic acid (PAPU) during the peri-operative period. METHODS: Twenty post-menopausal women with breast cancer undergoing mastectomy were randomized into a double blind, placebo-controlled, parallel group pilot study. PAPU (150 mg) or placebo was given intravenously the day prior to surgery (D -1), the day of surgery (D 0) and post-operatively on days (D 1, 3, 5, 7 and 14). Blood samples were collected on eight different days (D -2, -1, 0, 1, 2, 4, 6 and 18). CRP was significantly elevated in the PAPU group (P<0.05) on days 2 and 4, when compared with patients receiving placebo. The serum levels of cytokines believed to induce hepatic APRs, were also measured. RESULTS: The serum concentration of IL-6 was elevated on days 1, 2, 4 and 6 (P<0.05), TNF- alpha and IL-1 beta levels were increased on days 1 and 2 (P<0.05), respectively, while the serum level of soluble interleukin-2 receptor (sIL-2R) was elevated above the baseline on days 0, 2, 4, 6 and 18 in the PAPU group, when compared with the baseline. CONCLUSIONS: This modulation of acute phase response may have important implications for patients with cancer undergoing surgery.

Adjuvants, Immunologic↗

PubMed1999

Automated system for purification of dye-terminator sequencing products eliminates up-stream purification of templates.

The quality of sequencing results is to a large extent determined by the purity of the template and the purification of the sequencing products. Fragments that can act as unspecific primers and templates are removed before gel analysis, and the background of unspecific signals is highly reduced. Purification of the sequencing products is needed to remove salts, nucleotides, proteins and template DNA that can interfere with the gel separation. We have developed a product, DYNAPURE Dye Terminator Removal, that specifically isolates and purifies the sequencing products in 10 min. The method is based on biotinylated sequencing primers and super-paramagnetic streptavidin beads. A PCR product is sequenced using a biotinylated sequencing primer, and the sequencing products are then bound to streptavidin beads in a 5-min reaction. The bead-DNA complexes are magnetically separated from the rest of the solution, and the remaining buffer constituents are washed away with TE buffer or with 70% ethanol. The whole procedure can be automated on liquid-handling robots fitted with a magnet station. The method eliminates purification of templates before cycle sequencing.

Automation↗

PubMed1999

Linkage and association analysis of susceptibility regions on chromosomes 5 and 6 in 106 Scandinavian sibling pair families with multiple sclerosis.

In the genetically homogeneous Scandinavian population, we have investigated chromosome 5 and the HLA (human leukocyte antigen) region on chromosome 6p21 by applying linkage and association analyses on 106 white sibling pair families with multiple sclerosis. The importance of genes within the HLA region for the susceptibility of multiple sclerosis has previously been reported. More recently, findings have suggested importance of regions on chromosome 5. Half of chromosome 5 was analyzed by using 14 microsatellite markers and a susceptibility region with a maximum LOD score of 1.1 was identified. Chromosome 6 was analyzed by HLA-DR typing and using the TNF alpha microsatellite marker. A peak maximum LOD score of 2.0 was found at the HLA-DR marker. Association studies were made for all the markers, comparing 106 probands from the sibling pairs with 100 unrelated controls. None of the markers on chromosome 5 showed significant association with multiple sclerosis, whereas strong association between multiple sclerosis and DR2 was found, with an odds ratio of 3.7 (p < 10(-5)). It is surprising that association was not seen for any of the TNF alpha alleles including the 121-bp allele, although this allele was in positive linkage disequilibrium with DR2 in both patients and controls. Our results support the existence of multiple sclerosis susceptibility loci on chromosomes 5p and 6p21.

Chromosome Mapping↗