Detecting antithrombin deficiency may be a difficult task--more than one test is necessary.
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Antithrombins↗
Biomedical subjects
S Pedersen
Publications and source records attributed to S Pedersen.
Interactions of O(2) with Pd nanoparticles on alpha-Al(2)O(3)(0001) at low and high O(2) pressures.
The interaction of O(2) with small Pd particles (2-10 nm) supported on an alpha-Al(2)O(3)(0001) single crystal under both ultrahigh vacuum (UHV) and high-pressure conditions has been studied by temperature-programmed desorption (TPD), temperature-programmed low-energy ion scattering (TP-LEIS), and X-ray photoelectron spectroscopy (XPS). A low O(2) exposure (30 L) at 500 K leads to surface oxygen adatoms on the Pd nanoparticles, which desorb in TPD as O(2) in a peak at approximately 880 K. Surface O adatoms on the smallest Pd particles move to subsurface sites starting at 400 K, and they almost all move subsurface by approximately 750 K, desorbing mainly at considerably higher temperature. The dominant oxygen species above 700 K is subsurface, implying that it is more stable than oxygen adatoms on Pd. Exposures of the Pd nanoparticles to 25 Torr O(2) at 373-473 K readily convert the Pd to a species whose Pd XPS peak shifts by the same amount as the binding energy difference between bulk Pd and bulk PdO. We attribute this to PdO nanoparticles (or a thin film of PdO on or under the Pd for the larger particles). The decomposition of the PdO on these nanoparticles to Pd in an equilibrium O(2) pressure of 10-7 Torr does not occur until approximately 750 K, or approximately 200 K higher than the equilibrium decomposition of bulk PdO. This is attributed to the higher energy of Pd nanoparticles compared to bulk Pd and, for the larger particles, to the adhesion energy of the PdO film to the Pd, both of which stabilize the PdO on these Pd nanoparticles relative to bulk PdO. This PdO-like film on the larger particles may be similar to the ordered oxide thin film previously reported to form on Pd(111) but may also reside at the alpha-Al(2)O(3) interface and be partially stabilized by adhesion to this interface.
Journal Article↗
Modulation of the soft tissue reactions to percutaneous orthopaedic implants.
To evaluate soft tissue reactions and biofilm formation on percutaneous external fixator screws coated with diamond-like carbon (DLC) and hydroxyapatite (HA) coatings on stainless-steel (SS) pins in an ovine loaded osteotomy model, an Orthofix external fixator was used to stabilize a 3-mm tibial midshaft osteotomy with six tapered pins inserted into the right tibia of 32 skeletally mature Friesland ewes. Animals were divided into four groups; SS, fully coated HA, DLC, and HA-coated threads. At 10 weeks, specimens were harvested and the pins were removed en bloc to examine the interfaces between the surface coatings and the tissues. Fully coated HA pins had a significantly higher percentage of dermal contact with the pin surface than HA-coated threads (p=0.028). The presence of a biofilm was evident on all pin surfaces except DLC-coated pins. Significantly greater numbers of bacteria were present on fully coated HA and plain stainless-steel pins compared with DLC. The surface of DLC-coated pins had a significantly lower number of bacterial colonies compared to SS (p=0.028) and fully coated HA pins (p=0.005). Fully coated HA pins have greater dermal attachment to the pin surface than the other pin coatings investigated. DLC-coated pins have the potential to prevent biofilm formation and bacterial colonization that may reduce infection and consequent pin loosening. An external fixator pin that is partially coated with HA to encourage bone and soft tissue integration and with DLC to reduce biofilm formation is advocated.
Animals↗
A comparative study of inhaled ciclesonide 160 microg/day and fluticasone propionate 176 microg/day in children with asthma.
Ciclesonide (CIC) is an inhaled corticosteroid (ICS) with high anti-inflammatory activity and low incidence of local and systemic adverse effects. The objective of this study was to compare the efficacy and safety of CIC with fluticasone propionate (FP) in children and adolescents with persistent asthma. This was a 12-week, randomized, double blind, parallel-group study. After a 2-to 4-week baseline period, a total of 556 children (ages 6-15 years) with asthma (forced expiratory volume in 1 sec [FEV(1)], 50% to 90% predicted) were treated twice daily with CIC 80 microg (ex-actuator, equivalent to 100 microg ex-valve) or FP 88 microg (ex-actuator, equivalent to 100 microg ex-valve) administered via a hydrofluoroalkane-propelled metered-dose inhaler. A statistically significant increase from baseline was observed in FEV(1) for both CIC (285 +/- 16 ml) and FP (285 +/- 15 ml) (P < 0.0001 for both) and in morning and evening peak expiratory flow (P < 0.0001 for both). Significant improvements were seen in asthma symptoms, use of rescue medication, and asthma symptom-free days in both treatment groups, without any differences between the treatment groups in changes from baseline. Two FP-treated patients experienced oral candidiasis and one patient experienced voice alteration. Creatinine-adjusted 24-hr urine cortisol levels increased from baseline levels by 10% in the CIC group (P < 0.05) and by 6% in the FP group (not significant). The efficacy and safety of CIC 160 microg/day were comparable to those of FP 176 microg/day in children with asthma.
Administration, Inhalation↗
Low frequency of Parkin, Tyrosine Hydroxylase, and GTP Cyclohydrolase I gene mutations in a Danish population of early-onset Parkinson's Disease.
Autosomal recessive Parkinson's disease (PD) with early-onset may be caused by mutations in the parkin gene (PARK2). We have ascertained 87 Danish patients with an early-onset form of PD (age at onset < or =40 years, or < or =50 years if family history is positive) in a multicenter study in order to determine the frequency of PARK2 mutations. Analysis of the GTP cyclohydrolase I gene (GCH1) and the tyrosine hydroxylase gene (TH), mutated in dopa-responsive dystonia and juvenile PD, have also been included. Ten different PARK2 mutations were identified in 10 patients. Two of the patients (2.3%) were found to have homozygous or compound heterozygous mutations, and eight of the patients (9.2%) were found to be heterozygous. A mutation has been identified in 10.4% of the sporadic cases and in 15.0% of cases with a positive family history of PD. One patient was found to be heterozygous for both a PARK2 mutation and a missense mutation (A6T) in TH of unknown significance. It cannot be excluded that both mutations contribute to the phenotype. No other putative disease causing TH or GCH1 mutations were found. In conclusion, homozygous, or compound heterozygous PARK2 mutations, and mutations in GCH1 and TH, are rare even in a population of PD patients with early-onset of the disease.
Adult↗
Country-specific cost-effectiveness of early intervention with budesonide in mild asthma.
Early intervention with budesonide is an effective strategy for mild persistent asthma, which has been shown to provide additional clinical benefits at a low incremental cost using USA cost data. The present authors analysed whether this strategy would be cost-effective using cost data for other countries. Based on the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As Regular Therapy (START) in early asthma study (comparing budesonide and placebo combined with usual asthma therapy), the cost-effectiveness was estimated separately for eight different countries, from both healthcare payer and societal perspectives, of adding budesonide to usual asthma therapy. Local unit costs were applied to data for the total trial population. Incremental cost-effectiveness ratios (ICER) were estimated as cost per symptom-free day (SFD) gained. Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare payer perspective, budesonide would reduce the total cost of asthma care in Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be cost-saving in Australia, Canada and Sweden. In conclusion, for countries where costs with budesonide are higher, the policy implication has to be determined by that health system's willingness to pay for an additional symptom-free day. However, where budesonide therapy increases symptom-free days and reduces total costs, the policy conclusion clearly favours early intervention.
Administration, Inhalation↗
Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma.
A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this. A randomised, double-blind, crossover study was used to compare the effect of placebo, HFA-BDP 50 microg or 100 microg given q.d. (QVAR(TM) Autohaler(TM); 3M Pharmaceuticals, St. Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide (eNO). After a 14-day run-in, 25 children (5-14 yrs old) entered three 4-week treatment periods, separated by a 1-week washout. After each period, the fall in forced expiratory volume in one second (FEV1), after an exercise test, and eNO were measured. Significant treatment effects with no carry-over or period effects were seen for both eNO and maximum fall in FEV1 after exercise. Differences were seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and either dose of HFA-BDP, but not between the two active doses (50 microg: fall in FEV1=20.8%, eNO=9.3 ppb; 100 microg: fall in FEV1=20.9%, eNO=8.9 ppb). In conclusion, low q.d. doses of hydrofluoroalkane-beclomethasone dipropionate reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further studies are needed to assess whether q.d. administration of beclomethasone dipropionate is as effective as b.i.d. administration.
Administration, Inhalation↗
Influence of particle size on lung deposition and pharmacokinetics of beclomethasone dipropionate in children.
We set out to evaluate lung deposition, systemic availability, and basic pharmacokinetic parameters of beclomethasone dipropionate (BDP) in children with chronic asthma. Plasma levels of BDP, 17 and 21 beclomethasone monopropionate (17-BMP and 21-BMP), and beclomethasone were measured after an intravenous infusion of 60 microg BDP and after inhalation of A) 100 microg HFA-BDP, B) 200 microg HFA-BDP, C) 200 microg HFA-BDP after ingestion of charcoal to block gastrointestinal (GI) absorption of drug, and D) 400 microg CFC-BDP. A breath-actuated pMDI (Autohaler) was used for HFA inhalations, and a pMDI with a large volume spacer (Volumatic) for CFC inhalations. Treatments A-D were given in a randomized, cross-over design. Fourteen patients aged 10-14 years completed all 5 study days. The mean systemic bioavailabilities in percent of dose leaving the canister valve (ex-valve) were 70% (100 HFA), 74% (200 HFA), 60% (200 HFA + charcoal), and 27% (400 microg CFC). After HFA treatment, 82% of the systemically available dose was absorbed through the lungs, and 18% from the gastrointestinal tract. The estimated bioavailability of BDP from the GI tract was 68%. BDP was metabolized to 17-BMP within minutes. Mean steady-state volume of distribution of 17-BMP was 84 L, and the mean terminal half-life (T((1/2))) after the four inhalations was 2.7 hr (range, 2.2-3.7 hr). Mean T((1/2)) and clearance after i.v. administration were 1.7 hr and 0.9 L/min, respectively. The HFA Autohaler delivers approximately three times as much BDP to the intrapulmonary airways as a CFC-pMDI with a large volume spacer.
Administration, Inhalation↗
[Respiratory diseases in European farmers-II. Part of the European farmers' project].
BACKGROUND: The aim of the European Farmers' Project was to estimate the prevalence of respiratory diseases in farmers across Europe. Furthermore, risk factors for respiratory symptoms in different parts of agricultural production should be assessed. METHODS: In the first part of the study, 7496 farmers from four European countries answered a written questionaire. Of these, 229 were visited at their farms in the second part of the survey. On site, spirometry, allergy tests, as well exposure measurements were performed. RESULTS: Farmers with animal production had a significantly lower prevalence of allergic diseases than the general population. In contrast, the prevalence of chronic phlegm was higher in animal farmers. Organic dust toxic syndrome (ODTS) was a major predictor of chronic bronchitis. It was indicated that allergens found in the working environment could be transfered to the living environment of the farmer. Poor ventilation as well as high temperatures inside the animal buildings were shown to have a negative impact on respiratory symptoms and lung function parameters. CONCLUSION: Animal farmers are at high risk of chronic bronchitis. Intervention studies on the efficacy of different types of ventilation are now warranted. Furthermore, prospective studies on the associaton between ODTS and COPD should be done.
Adult↗
Impact of protein energy malnutrition on Trichuris suis infection in pigs concomitantly infected with Ascaris suum.
The objective of this experiment was to investigate a possible interaction between protein and energy malnutrition (PEM) and intestinal nematode infections. We report on a 3 x 2 factorial study in which pigs were fed either a low protein energy (LPE), low protein (LP) or a normal protein energy (NPE) diet, and 6 weeks later inoculated with Trichuris suis (4000 infective eggs). Secondarily, in order to obtain a polyparasitic status, pigs were concomitantly inoculated with Ascaris suum (600 infective eggs). The number of T. suis-infected pigs was higher in LP pigs compared with NPE pigs (100 versus 58%; P = 0.037), although the differences in median T. suis worm burdens between groups at necropsy 10 weeks post-infection (p.i.) (LPE: 795; LP: 835; NPE: 48 worms; P = 0.33) were not significant. Interestingly, only T. suis in NPE were highly aggregated (k = 0.44), in contrast to a more uniform distribution among pigs in LPE (k = 1.43) and LP (k = 1.55) i.e. the majority of pigs harboured moderate worm burdens in LPE and LP, while most pigs had few or no worms in NPE. Further, T. suis worms in the LPE and LP groups were decreased in length (mean: LPE: 23.5 mm; LP: 24.3 mm; NPE: 29.4 mm; P = 0.004). The pre-patency period of T. suis was also extended in the LPE and LP groups, as reflected by lower faecal egg output at week 6 (P = 0.048) and/or 7 p.i. (P = 0.007). More A. suum worms were recovered from LP compared with the NPE group (mean: 5.4 versus 0.6; P = 0.040); this was accompanied by a higher faecal egg output in the former (P = 0.004). The low protein diets resulted in lower pig body weight gains, serum albumin, haemoglobin and packed cell volume (PCV) levels as well as diminished peripheral eosinophil counts. Infection significantly altered these parameters in the low protein groups, i.e. the pathophysiological consequences of infection were more severe in the PEM pigs. These results demonstrate that reduced protein in the diet leads to malnourishment of both the host pigs and T. suis, and compromises the pig's ability to resist infection by T. suis and A. suum.
Animals↗
Long-term outcomes in paediatric asthma.
Over the years the aims of asthma management have changed markedly from effective prednisolone treatment of symptoms and exacerbations towards more use of continuous prophylactic treatment. With our new understanding of the disease and its management definition of the aims of treatment and assessment of optimal asthma control have become much more complex. Even in times of evidence-based medicine our asthma management is based upon findings of effects on various outcomes in somewhat short-term (<1 year) controlled studies. However, assumptions about long-term effects upon the basis of findings in such studies should be made with great caution. Good examples of this are studies which assess the risk of systemic effects and clinical adverse effects of inhaled corticosteroids. From such studies it has become clear that systemic effects detected in short-term trials may have no predictive value of long-term adverse effects. Thus steroid-induced changes in lower leg growth rates assessed by knemometry do not predict long-term statural growth. Moreover, steroid-induced changes in statural growth over 1 year are not predictive of effects upon attained adult height. In contrast, reduced growth caused by uncontrolled asthma disease also seems to affect attained adult height adversely. These findings suggest that long-term outcomes should play a larger role when future asthma management strategies are decided. Some important long-term outcomes of asthma management in children include cure or remission of the disease, prevention of complications of the disease (airway remodelling, adverse effects upon growth/adult height, peak bone mineral density, physical impairment and psychosocial development) or its pharmacological management (adverse effects upon adult height, peak bone mineral density). More controlled long-term studies (several years) are needed to provide a better understanding of how these outcomes are best achieved.
Adrenal Cortex Hormones↗
Host age influence on the intensity of experimental Trichuris suis infection in pigs.
The impact of age-related resistance on the regulation of population dynamics of adult Trichuris suis was investigated in an experimental pig model. Helminth-naïve pigs varying in age from five weeks to four years were infected with T. suis to determine susceptibility to infection. Sows had a significantly lower establishment of adult T. suis worms compared with weaner pigs. Adult worm populations were highly overdispersed in both sows and grower pigs contrasted by a more even distribution among weaner pigs. Sows had significantly lower worm fecundities compared to weaner and grower pigs; T. suis from grower pigs, in turn, had reduced fecundity compared to worms in weaner pigs. In conclusion, we provide the first controlled experimental evidence that age-related resistance to T. suis occurs in pigs.
Age Factors↗
Frequent musculoskeletal symptoms and reduced health-related quality of life among industrial workers.
The high percentage of musculoskeletal symptoms (MSS) found in studies of general populations and various occupational groups underlines the need to distinguish between severely and mildly affected individuals. To investigate associations between MSS and quality of life, we examined the frequency of MSS on a five-point scale, health-related quality of life (SF-36) and sickness absence among 5654 workers in the aluminium industry. High frequencies of MSS from all body parts were related to lower scores on the SF-36 and increased sickness absence. This relationship was strongest for MSS from the lower back. Workers who reported low back MSS 'very often' had a mean role--physical score equivalent to that of the 15th percentile of the general population. These results show that workers who reported MSS often or very often were severely affected, and this scale can therefore be used to distinguish individuals at high risk for reduced health-related quality of life and sickness absence.
Absenteeism↗
Do inhaled corticosteroids inhibit growth in children?
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Administration, Inhalation↗
Reduction and alkylation of proteins in preparation of two-dimensional map analysis: why, when, and how?
The standard procedure adopted up to the present in proteome analysis calls for just reduction prior to the isoelectric focusing/immobilized pH gradient (IEF/IPG) step, followed by a second reduction/alkylation step in between the first and second dimension, in preparation for the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) step. This protocol is far from being optimal. It is here demonstrated, by matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry, that failure to reduce and alkylate proteins prior to any electrophoretic step (including the first dimension) results in a large number of spurious spots in the alkaline pH region, due to "scrambled" disulfide bridges among like and unlike chains. This series of artefactual spots comprises not only dimers, but an impressive series of oligomers (up to nonamers) in the case of simple polypeptides such as the human alpha- and beta-globin chains, which possess only one (alpha-) or two (beta-) -SH groups. As a result, misplaced spots are to be found in the resulting two-dimensional (2-D) map, if performed with the wrong protocol. The number of such artefactual spots can be impressively large. In the case of analysis of complex samples, such as human plasma, it is additionally shown that failure to alkylate proteins results in a substantial loss of spots in the alkaline gel region, possibly due to the fact that these proteins, at their pI, regenerate their disulfide bridges with concomitant formation of macroaggregates which become entangled with and trapped within the polyacrylamide gel fibers. This strongly quenches their transfer in the subsequent SDS-PAGE step.
Alkylation↗
The inhaled Steroid Treatment as Regular Therapy in early asthma (START) study: rationale and design.
Although the beneficial effects of treatment with inhaled steroids in asthma are widely accepted, the role of early intervention in patients with mild asthma remains unsettled. Conventional efficacy trials are often of short duration and involve highly selected patient populations that exclude many patients typical of those encountered in routine clinical practice. Hence, a large "real-world" effectiveness study is needed to evaluate the benefits of early intervention with inhaled steroids in patients with mild, persistent asthma. In the START (inhaled Steroid Treatment As Regular Therapy in early asthma) study, patients ages 6-60 years, from 31 countries and districts worldwide with mild persistent asthma, have been randomized to once-daily treatment with budesonide, 200 microg (for patients < 11 years) or 400 microg (for patients > or = 11 years), or placebo via Turbuhaler for 3 years. The double-blind treatment period will be followed by a 2-year period of open budesonide treatment. Throughout the study, other asthma medication including glucocorticosteroids can be given as judged appropriate by the investigator. Lung function will be measured by spirometry using standardized techniques at 3-month intervals throughout the study, and bronchodilator reversibility will be measured annually. The primary outcome measures are the time to the first severe asthma-related event during the first 3 years of the study and the change in postbronchodilator forced expiratory volume in 1 second (FEV(1)) from baseline during the entire 5-year study period. These measures have been chosen to reflect the progression of mild asthma toward more severe asthma and the extent of irreversible airflow limitation, which should reflect the degree of airway remodeling.
Acute Disease↗
Whipworm-nutrition interaction.
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Animals↗
Effect of iron deficiency on Trichuris suis and Ascaris suum infections in pigs.
The objective of this experiment was to detect a possible interaction between iron deficiency and intestinal nematode infections. We report on a 2 x 2 study where thirty-one 10-week-old pigs fed a low or a normal iron diet were infected with both Trichuris suis (4500 eggs) and Ascaris suum (1200 eggs). No significant difference was detected between diet groups with respect to parasitological parameters for A. suum or the total number of adult T. suis recovered at necropsy 10 weeks p.i. However, in the low iron group T. suis were located more proximally and the worms were increased in length. A higher proportion of pigs with initial faecal egg excretion at 6 weeks p.i. was observed in the low iron group, indicating a shortened pre-patency period. Worm fecundity and total faecal egg excretion were also highest in the low iron group. A significant correlation was found between female worm length and fecundity. The peripheral eosinophil counts were diminished in the low iron host groups. The infected low iron group experienced more severe pathophysiological changes in terms of hypoalbuminaemia and decreases in erythrocyte volumes. A significant inverse correlation existed between iron content in the bone-marrow and liver (body) store. In conclusion, iron deficiency increased the severity of T. suis infection in pigs.
Anemia, Iron-Deficiency↗