| 1. |
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| 2. |
- Blomquist, Göran K., et al.
(författare)
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Separation of fungal propagules by partition in aqueous polymer 2-phase systems
- 1984
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Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 47:6, s. 1316-1318
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Tidskriftsartikel (refereegranskat)abstract
- Conidia of Penicillium chrysogenum and Penicillium frequentans and sporangiospores of Rhizopus rhizopodiformis, Rhizomucor pusillus, and Mucor racemosus were subjected to partition in aqueous polymer two-phase systems. The partition behavior differed drastically between the conidia of the two Penicillium species and the sporangiospores of the three species of phycomycetes. This difference in partition behavior can be used for purification of fungi belonging to different taxonomical groups. P. frequentans was completely separated from M. racemosus by two extractions, whereas four extractions were needed to purify M. racemosus. This method was used on an air sample from a locality where wood fuel chips are handled. The conidia of the fungi Trichoderma viride and Rhizopus rhizopodiformis were removed completely by only two extractions.
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| 3. |
- Dahlén, Gunnar, 1944, et al.
(författare)
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A retrospective study on the microbiology in patients with oral complaints and oral mucosal lesions.
- 2009
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Ingår i: Oral diseases. - : Wiley. - 1601-0825 .- 1354-523X. ; 15:4, s. 265-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to microbiologically analyze oral mucosal samples collected during 2 years from patients with oral mucosal complaints. MATERIALS AND METHODS: Mucosal scraping samples were taken from 297 patients and semiquantified by culture for detection of opportunistic microorganisms e.g. Staphylococcus aureus, enterococci, aerobic Gram-negative bacilli (AGNB) and yeasts. Antibiotic susceptibility test was performed. RESULTS: Altogether 297 patients were sampled (mean age 56.8 +/- 20.7). Among the 110 patients with known medical condition, 48 were systemically immunocompromised, 35 had systemic diseases, and 27 had only local oral complaints. Opportunists in moderate growth or more were present commonly in all three groups and most frequent in the immunocompromised patients (66.7%). Candida species were the most frequent opportunist (68.8%), however, their level was low and combinations with bacterial opportunists were common (39.6%). All bacterial opportunists tested were antibiotic multiresistant. Follow-up samples were collected in 23 cases out of which seven showed still presence of opportunists in heavy growth despite repeated treatment with ciprofloxacin. CONCLUSIONS: This study showed a frequent presence of bacterial and fungal opportunists in patients with oral mucosal complaints, which were most common in immunocompromised individuals, however, also frequent in patients with local oral complaints only. Systematic evaluation of different treatment strategies is needed.
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| 4. |
- Darreh-Shori, T., et al.
(författare)
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Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:2, s. 168-184
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months Galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by C-11-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.
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| 5. |
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| 6. |
- Engler, Henry, et al.
(författare)
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Two-year follow-up of amyloid deposition in patients with Alzheimer's disease
- 2006
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 129:Pt 11, s. 2856-2866
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Tidskriftsartikel (refereegranskat)abstract
- Beta amyloid is one of the major histopathological hallmarks of Alzheimer's disease. We recently reported in vivo imaging of amyloid in 16 Alzheimer patients, using the PET ligand N-methyl[11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole (PIB). In the present study we rescanned these 16 Alzheimer patients after 2.0 +/- 0.5 years and have described the interval change in amyloid deposition and regional cerebral metabolic rate for glucose (rCMRGlc) at follow-up. Sixteen patients with Alzheimer's disease were re-examined by means of PET, using PIB and 2-[18F]fluoro-2-deoxy-d-glucose (FDG) after 2.0 +/- 0.5 years. The patients were all on cholinesterase inhibitor treatment and five also on treatment with the N-methyl-d-aspartate (NMDA) antagonist memantine. In order to estimate the accuracy of the PET PIB measurements, four additional Alzheimer patients underwent repeated examinations with PIB within 20 days (test-retest). Relative PIB retention in cortical regions differed by 3-7% in the test-retest study. No significant difference in PIB retention was observed between baseline and follow-up while a significant (P < 0.01) 20% decrease in rCMRGlc was observed in cortical brain regions. A significant negative correlation between rCMRGlc and PIB retention was observed in the parietal cortex in the Alzheimer patients at follow-up (r = 0.67, P = 0.009). A non-significant decline in Mini-Mental State Examination (MMSE) score from 24.3 +/- 3.7 (mean +/- standard deviation) to 22.7 +/- 6.1 was measured at follow-up. Five of the Alzheimer patients showed a significant decline in MMSE score of >3 (21.4 +/- 3.5 to 15.6 +/- 3.9, P < 0.01) (AD-progressive) while the rest of the patients were cognitively more stable (MMSE score = 25.6 +/- 3.1 to 25.9 +/- 3.7) (AD-stable) compared with baseline. A positive correlation (P = 0.001) was observed in the parietal cortex between Rey Auditory Verbal Learning (RAVL) test score and rCMRGlc at follow-up while a negative correlation (P = 0.018) was observed between RAVL test and PIB retention in the parietal at follow-up. Relatively stable PIB retention after 2 years of follow-up in patients with mild Alzheimer's disease suggests that amyloid deposition in the brain reaches a plateau by the early clinical stages of Alzheimer's disease and therefore may precede a decline in rCMRGlc and cognition. It appears that anti-amyloid therapies will need to induce a significant decrease in amyloid load in order for PIB PET images to detect a drug effect in Alzheimer patients. FDG imaging may be able to detect a stabilization of cerebral metabolism caused by therapy administered to patients with a clinical diagnosis of Alzheimer's disease.
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| 7. |
- Forsberg, Anton, et al.
(författare)
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PET imaging of amyloid deposition in patients with mild cognitive impairment
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1456-1465
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Tidskriftsartikel (refereegranskat)abstract
- It is of great clinical value to identify subjects at a high risk of developing AD. We previously found that the amyloid positron emission tomography (PET) tracer PIB showed a robust difference in retention in the brain between AD patients and healthy controls (HC). Twenty-one patients diagnosed with MCI (mean age 63.3 ± 7.8 (S.D.) years) underwent PET studies with 11C-PIB, and 18F-fluoro-deoxy-glucose (FDG) to measure cerebral glucose metabolism, as well as assessment of cognitive function and CSF sampling. Reference group data from 27 AD patients and 6 healthy controls, respectively, were used for comparison. The mean cortical PIB retention for the MCI patients was intermediate compared to HC and AD. Seven MCI patients that later at clinical follow-up converted to AD (8.1 ± 6.0 (S.D.) months) showed significant higher PIB retention compared to non-converting MCI patients and HC, respectively (ps < 0.01). The PIB retention in MCI converters was comparable to AD patients (p > 0.01). Correlations were observed in the MCI patients between PIB retention and CSF Aβ1-42, total Tau and episodic memory, respectively.
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| 8. |
- Forsberg, Anton, et al.
(författare)
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The use of PIB-PET as a dual pathological and functional biomarker in AD
- 2012
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Ingår i: Biochimica et Biophysica Acta - Molecular Basis of Disease. - : Elsevier BV. - 0925-4439 .- 1879-260X. ; 1822:3, s. 380-385
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid imaging with positron emission tomography (PET) is presently used in Alzheimer's disease (AD) research. In this study we investigated the possibility to use early frames (ePIB) of the PIB scans as a rough index of CBF by comparing normalised early PIB values with cerebral glucose metabolism (rCMRglc). PIB-PET and FDG-PET were performed in 37 AD patients, 21 subjects with mild cognitive impairment (MCI) and 6 healthy controls (HC). The patients were divided based on their PIB retention (amyloid load) as either PIB positive (PIB+) or PIB negative (PIB-). Data of the unidirectional influx K-1 from a subset of the subjects including 7 AD patients and 3 HC was used for correlative analysis. Data was analysed using regions of interest (ROI) analysis. A strong, positive correlation was observed across brain regions between K-1 and ePIB (r=0.70: p <= 0.001). The ePIB values were significantly lower in the posterior cingulate (p <= 0.001) and the parietal cortices (p = 0.002) in PIB+ subjects compared to PIB-, although the group difference were stronger for rCMRglc in cortical areas (p <= 0.001). Strong positive correlations between ePIB and rCMRglc were observed in all cortical regions analysed, especially in the posterior cingulate and parietal cortices (p <= 0.001). A single dynamic PIE-PET scan may provide information about pathological and functional changes (amyloidosis and impaired blood flow). This might be important for diagnosis of AD, enrichment of patients in clinical trials and evaluation of treatment effects.
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| 9. |
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| 10. |
- Johansson, Anders, et al.
(författare)
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Evidence for astrocytosis in ALS demonstrated by 11C(L)-deprenyl-D2 PET
- 2007
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 255:1-2, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To use deuterium-substituted [11C](l)-deprenyl PET to depict astrocytosis in vivo in patients with amyotrophic lateral sclerosis (ALS). Background: In human brain, the enzyme MAO-B is primarily located in astrocytes. l-deprenyl binds to MAO-B and autoradiography with 3H-l-deprenyl has been used to map astrocytosis in vitro. Motor neuron loss in ALS is accompanied by astrocytosis and astrocytes may play an active role in the neurodegenerative process. Deuterium-substituted [11C](l)-deprenyl PET provides an opportunity to localize astrocytosis in vivo in the brain of patients with ALS. Methods: Deuterium-substituted [11C](l)-deprenyl PET was performed in seven patients with ALS and seven healthy control subjects. Results: Increased uptake rate of [11C](l)-deprenyl was demonstrated in ALS in pons and white matter. Conclusion: This study provides evidence that astrocytosis may be detected in vivo in ALS by the use of deuterium-substituted [11C](l)-deprenyl PET though further studies are needed to determine whether deuterium-substituted [11C](l)-deprenyl binding tracks disease progression and reflects astrocytosis.
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| 11. |
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| 12. |
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| 13. |
- Lewis, Jeffrey, et al.
(författare)
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PFAS – A threat for groundwater and drinking water supply in Sweden?
- 2015
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Ingår i: EGU General Assembly 2015. ; 17
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Perfluoroalkyl substances (PFAS) are a group of anthropogenic environmental pollutants that are widely distributed in the global environment. They have multiple industrial uses, including water repellents in clothing, paper coatings and firefighting foam. According to a study released by the Environmental Directorate of the OECD, they are persistent, bioaccumulative and toxic to mammalian species (OECD, 2002). In some municipal drinking water wells in Sweden, measured concentrations of PFAS found to be several hundred times higher than the allowed threshold values. This has created a huge public concern and has recently attracted much media attention in Sweden (e.g. Afzelius et al., 2014; Bergman et al., 2014; Lewis et al., 2014). PFAS findings raised questions such as “What can we do to solve the problem?” When it comes to drinking water, there are a number of techniques that can ensure that PFAS levels are reduced to acceptable levels. This may be a costly challenge, but from a technical point of view it is possible. To ensure the safety of drinking water from a public health perspective is obviously a top priority. However, international experience shows that the cost of cleaning up PFAS in groundwater may be significantly higher than continuously treat drinking water in water works. Approximately fifty percent of Sweden’s drinking water comes from groundwater. As a result, there are several ongoing and planned PFAS-related environmental and drinking-water investigations in Sweden. Many aquifers that supply municipal water plants are located in areas of sand and gravel deposits. Such soils have relatively high permeabilities, which permits extraction of large volumes of water. However, the downside to high permeabilities is that they also allow dissolved contaminants as PFAS to spread over large areas. If one disregards the health risks linked to its presence in drinking water, PFAS have an impact on three of Sweden’s national environmental quality objectives, namely, A Non-Toxic Environment, Flourishing Lakes and Streams and Good-Quality Groundwater. Although the survey of PFAS in our groundwater supplies will take time, it is feasible. Much research in the field of hydrogeology and geochemistry remains before a viable and cost-effective groundwater remediation method can be operational. Until then, it is essential that measures are taken to identify the present distribution and magnitude of PFAS in groundwater and prevents its further spread in our most important aquifers. Afzelius, H. et al., 2014. Vågar vi dricka kranvattnet? (Do we dare drinking tap water?), Svenska Dagbladet. Bergman, Å., Hansson, S.O., Hellsten, E., 2014. En miljöskandal av historiska mått (An environmental scandal of historic proportions), Svenska Dagbladet. Lewis, J. et al., 2014. Kartlägg det förorenade dricksvattnet (Survey the contaminated drinking water), Svenska Dagbladet. OECD, 2002. Hazard Assessment of Perfluorooctane Sulfonate (PFOS) and its Salt.
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| 14. |
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| 15. |
- Lundquist, Pinelopi, et al.
(författare)
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5-hydroxy-L-[beta-C-11]tryptophan versus alpha-[C-11]methyl-L-tryptophan for positron emission tomography imaging of serotonin synthesis capacity in the rhesus monkey brain
- 2007
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 27:4, s. 821-830
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to compare two positron emission tomography (PET) tracers that were developed to follow serotonin (5HT) synthesis by performing sequential PET scanning of the same rhesus monkey (n=4) on the same day. α-[11C]Methyl-L-tryptophan ([11C]AMT) and 5-Hydroxy-L-[β-11C]tryptophan ([11C]HTP) are substrates in the first and second enzymatic steps, respectively, in the biosynthesis of 5HT. Regional net accumulation rate constants were derived from kinetic (two-tissue compartment model with irreversible tracer trapping) and graphic (Patlak) analyses, using the arterial plasma concentrations as input. The kinetic data analysis showed that the rate constant for the transfer of [11C]HTP into the brain (K1) was higher than that for [11C]AMT in the striatum and thalamus but was similar in other brain regions. The rate constant for tracer trapping (k3) was also higher for [11C]HTP than for [11C]AMT in the striatum (0.046±0.024 versus 0.019±0.006 min-1) and thalamus (0.039±0.013 versus 0.016±0.007 min-1). In agreement with previously reported regional HTP accumulation rates, the net accumulation rate constant (Kacc) for [11C]HTP was also higher in these regions than in other brain regions; this is in contrast to the uniform distribution of [11C]AMT Kacc values. This suggests that the regional net accumulation rates obtained with these two PET tracers will be of different magnitude, which might be related to the activity of each targeted enzyme.
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| 16. |
- Lundquist, Pinelopi, et al.
(författare)
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Effect on [11C]DASB binding after tranylcypromine-induced increase in serotonin concentration : positron emission tomography studies in monkeys and rats
- 2007
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Ingår i: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 61:6, s. 440-449
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Tidskriftsartikel (refereegranskat)abstract
- Several research groups have demonstrated that under specific conditions, in vivo neuroreceptor binding techniques can be used to measure acute changes in the concentrations of endogenous transmitters in the vicinity of neuroreceptors. The aim of this study was to investigate whether [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([11C]DASB) binding to the plasma membrane serotonin transporter (SERT) in the rhesus monkey and rat brain decreased after a pharmacologically-induced increase in the interstitial serotonin (5HT) concentration. Three rhesus monkeys were given repeated single boluses of [11C]DASB in sequential positron emission tomography (PET) experiments. Rats were given the tracer as a bolus dose plus a constant infusion. In vivo binding in both models was studied before and after presumably having increased interstitial 5HT concentrations using tranylcypromine (TCP), which inhibits the enzyme (monoamine oxidase, MAO), that degrades 5HT. The rat brain tissue was analyzed using high-performance liquid chromatography (HPLC) to determine the proportion of the PET signal comprising unchanged [11C]DASB. The binding of [11C]DASB in the thalamus decreased in both rhesus monkeys and rats after TCP administration. The possibility of using [11C]DASB as a tool for monitoring changes in endogenous serotonin concentrations merits further investigation.
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| 17. |
- Lundquist, Pinelopi, 1975-
(författare)
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Imaging and Quantification of Brain Serotonergic Activity using PET
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis investigates the potential of using positron emission tomography (PET) to study the biosynthesis and release of serotonin (5HT) at the brain serotonergic neuron. As PET requires probe compounds with specific attributes to enable imaging and quantification of biological processes, emphasis was placed on the evaluation of these attributes. The experiments established that the 5HT transporter radioligand [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile, [11C]DASB, is suitable for imaging and quantification of transporters in rats and rhesus monkeys. In addition, the binding of [11C]DASB in brain tissue is decreased when 5HT concentrations are increased by tranylcypromine administration. The sensitivity of [11C]DASB binding, under these experimental conditions, to increased endogenous 5HT concentrations demonstrates the potential of in vivo monitoring of 5HT release in rat and monkey models. The irreversible binding of 5-hydroxy-L-[β-11C]tryptophan, [11C]HTP, in the monkey brain was lower in the presence of NSD1015, which was used to inhibit the decarboxylase step in 5HT synthesis. [11C]HTP seems thus to have potential for tracking changes in the activity of this biosynthesis enzyme. In contrast, the accumulation of [11C]HTP was unaffected by clorgyline, which was used to inhibit metabolism of the probe in the brain. This appears to indicate that elimination of the main metabolite from the brain could be negligible and thus will not alter [11C]HTP quantification. The extent and distribution of the irreversible binding of a substrate for the first enzyme in 5HT formation, α-[11C]methyl-L-tryptophan, [11C]AMT, was different from those for [11C]HTP. This suggests that the two studied probe compounds provide estimates related to the enzyme activity of different steps in the 5HT biosynthesis pathway. A reference tissue version of the Patlak method for the analysis of data obtained by PET was also developed. This approach takes into account irreversible binding in the reference region and appears, therefore, to yield more reliable parameter estimates than the conventional reference Patlak analysis. The method is recommended for parameter estimation of [11C]HTP data when no metabolite-corrected plasma curve is available. Knowledge of altered 5HT synthesis and release in disease states and the consequences for effective pharmacotherapy can improve our knowledge of the aetiology of certain psychiatric and neurological diseases and enhance our ability to design more effective drugs.
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| 18. |
- Lundquist, Pinelopi, et al.
(författare)
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Validation studies on the 5-hydroxy-L-[beta-11C]-tryptophan/PET method for probing the decarboxylase step in serotonin synthesis
- 2006
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Ingår i: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 59:8, s. 521-531
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Tidskriftsartikel (refereegranskat)abstract
- The two-tissue compartment model, including irreversible trapping in the second compartment (2TCM) is used to describe the kinetics of 5-Hydroxy-L-[beta-(11)C]-tryptophan ([(11)C]HTP), a radioligand used in positron emission tomography (PET) for probing the second enzymatic step in the biosynthesis of serotonin. In this study, we examined the capacity of the model to track pharmacological changes in this biological process. We also investigated the potential loss of [(11)C]HTP-derived radioactivity during a PET study, since loss should be negligible not to alter quantification. Six rhesus monkeys were investigated using bolus [(11)C]HTP/PET methodology before and after pharmacological intervention. The second enzymatic step in serotonin synthesis was inhibited using the aromatic L-amino acid decarboxylase inhibitor NSD1015 (10 mg/kg). The extent of [(11)C]-derived radioactivity loss from the brain was studied by inhibition of the enzyme responsible for formation of the tissue metabolite, monoamine oxidase A, using clorgyline (2 mg/kg). After NSD1015, the uptake of [(11)C]HTP-derived radioactivity was increased in all the investigated brain regions, while the parameter used to reflect decarboxylase activity, the net accumulation rate constant (K(acc)), was decreased by 37% in the striatum, compared with baseline. Pretreatment with clorgyline did not change the brain uptake of [(11)C]HTP-derived radioactivity or K(acc). This study demonstrates that the 2TCM for [(11)C]HTP/PET is able to detect changes occurring during alteration of the biological process (i.e., the conversion of HTP to serotonin). Elimination of the radiotracer metabolite [(11)C]HIAA from the brain may be considered negligible if the PET study is limited to 60 min.
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| 19. |
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| 20. |
- Moosmayer, Stefan, et al.
(författare)
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KALK study: ultrasound guided needling and lavage (barbotage) with steroid injection versus sham barbotage with and without steroid injection - protocol for a randomized, double-blinded, controlled, multicenter study
- 2017
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Ingår i: BMC Musculoskeletal Disorders. - : BIOMED CENTRAL LTD. - 1471-2474. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: For the treatment of calcific tendinitis of the shoulder a variety of treatment regimes exist. Commonly used treatment measures include medication with oral analgesics, corticosteroid injections, extracorporeal shockwave therapy, ultrasound guided needling and lavage, and surgical treatment. Earlier cohort studies suggest that patients may benefit from these treatments, but there are few randomized studies and conflicting evidence about the effectiveness of the various treatments. In the present study we aim to compare the effectiveness of ultrasound guided needling and lavage (barbotage) together with a steroid injection to sham barbotage with and without an additional steroid injection. Methods: The study will be performed in six secondary-care institutions in Norway and Sweden. It is designed as a pragmatic, randomized, three-arm, parallel group, double-blinded, sham-controlled clinical trial with a 2-year follow-up. It will be performed on 210 patients, aged 30 years or older, presenting with painful arc, positive impingement sign and a calcium deposit amp;gt; 5 mm. Randomization to one of the three treatment options will be performed by using an online central randomization system. The three treatment groups are barbotage together with a subacromial steroid injection (the barbotage group), sham barbotage together with a subacromial steroid injection (the steroid group) or sham barbotage without a subacromial steroid injection (the placebo group). In the placebo group the steroid injection will be replaced by a short-acting local anaesthetic. Standardized home-based post-treatment physiotherapy will be performed by all patients for 8 weeks. Follow-ups are at 2 and 6 weeks, 4, 8, 12 and 24 months after treatment was given and will be performed with the patients and the outcome assessors blinded for group assignment. Primary outcome will be the Oxford shoulder score at 4 month follow-up. Secondary outcome measures are the QuickDASH upper extremity score, the EQ-5D-5L general health score and visual analogue scales for pain at rest, during activity, and at night. Discussion: The scientific evidence from this placebo-controlled trial will be of importance for future treatment recommendations in patients with calcific tendinitis.
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| 21. |
- Moosmayer, Stefan, et al.
(författare)
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Ultrasound guided lavage with corticosteroid injection versus sham lavage with and without corticosteroid injection for calcific tendinopathy of shoulder: randomised double blinded multi-arm study
- 2023
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Ingår i: BMJ. British Medical Journal. - : BMJ PUBLISHING GROUP. - 0959-8146 .- 0959-535X. ; 383
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare treatment effects between ultrasound guided lavage with corticosteroid injection and sham lavage with and without corticosteroid injection in patients with calcific tendinopathy of the shoulder. Design Pragmatic, three arm, parallel group, double blinded, sham controlled, randomised, superiority trial with repeated measurements over 24 months. Setting Six hospitals in Norway and Sweden. Participants 220 adults with calcific tendinopathy of the shoulder, persistent for at least three months. Interventions Ultrasound guided deposit lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (lavage+steroid); sham lavage plus subacromial injection of 20 mg triamcinolone acetonide and 9 mL 1% lidocaine hydrochloride (sham lavage+steroid); or sham lavage plus subacromial injection of 10 mL 1% lidocaine hydrochloride (sham). All patients received a physiotherapeutic treatment regimen consisting of four home exercises. Main outcome measures The primary outcome was the result on the 48 point scale (0=worst; 48=best) of the Oxford Shoulder Score (OSS) at four month follow-up. Secondary outcomes included measurements on the short form of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) and of pain intensity up to 24 months. The influence of the size of the deposit at baseline and of the persistence or disappearance of the deposit was investigated. Results Data from 218 (99%) participants were included in the primary analysis. Differences between groups on the OSS at four months were not significant: lavage+steroid versus sham 0.2 (95% confidence interval -2.3 to 2.8; P=1.0); sham lavage+steroid versus sham 2.0 (-0.5 to 4.6; P=0.35); lavage+steroid versus sham lavage+steroid -1.8 (-4.3 to 0.7; P=0.47). After four months, 143 patients with insufficient treatment effect received supplementary treatment. At 24 months, none of the study procedures was superior to sham. No serious adverse events were reported. Conclusions This study found no benefit for ultrasound guided lavage with a corticosteroid injection or for sham lavage with a corticosteroid injection compared with sham treatment in patients with calcific rotator cuff tendinopathy of the shoulder.th calcific rotator cuff tendinopathy of the shoulder.
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| 22. |
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| 23. |
- Razifar, Pasha, et al.
(författare)
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Principal component analysis with pre-normalization improves the signal-to-noise ratio and image quality in positron emission tomography studies of amyloid deposits in Alzheimer's disease
- 2009
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 54:11, s. 3595-3612
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Tidskriftsartikel (refereegranskat)abstract
- This study introduces a new approach for the application of principal component analysis (PCA) with pre-normalization on dynamic positron emission tomography (PET) images. These images are generated using the amyloid imaging agent N-methyl [C-11]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([C-11]PIB) in patients with Alzheimer's disease (AD) and healthy volunteers (HVs). The aim was to introduce a method which, by using the whole dataset and without assuming a specific kinetic model, could generate images with improved signal-to-noise and detect, extract and illustrate changes in kinetic behavior between different regions in the brain. Eight AD patients and eight HVs from a previously published study with [C-11] PIB were used. The approach includes enhancement of brain regions where the kinetics of the radiotracer are different from what is seen in the reference region, pre-normalization for differences in noise levels and removal of negative values. This is followed by slice-wise application of PCA (SW-PCA) on the dynamic PET images. Results obtained using the new approach were compared with results obtained using reference Patlak and summed images. The new approach generated images with good quality in which cortical brain regions in AD patients showed high uptake, compared to cerebellum and white matter. Cortical structures in HVs showed low uptake as expected and in good agreement with data generated using kinetic modeling. The introduced approach generated images with enhanced contrast and improved signal-to-noise ratio (SNR) and discrimination power (DP) compared to summed images and parametric images. This method is expected to be an important clinical tool in the diagnosis and differential diagnosis of dementia.
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| 24. |
- Richter, Jan Hinnerk, et al.
(författare)
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Li insertion in sol-gel prepared Mn-doped TiO2 studied by electron spectroscopy in ultrahigh vacuum
- 2007
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 111:8, s. 3459-3466
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Tidskriftsartikel (refereegranskat)abstract
- The properties of a sol-gel prepared Mn-modified TiO2 film have been studied with X-ray absorption spectroscopy (XAS) and photoelectron spectroscopy (PES) using synchrotron radiation. The chemical composition and oxidation state of the elements have been determined. The manganese content estimated by PES of the Mn-modified film is about 10% and both Mn2+ and Mn3+ are observed. Addition of Mn is found to modify the valence band edge. The Mn 3d states are found to extend about 1 eV into the TiO 2 band gap region. It is demonstrated that lithium insertion into the sol-gel film can be performed in a stepwise fashion in situ under ultrahigh vacuum (UHV) conditions. Lithium is distributed evenly throughout the entire film and leads to reduction of Mn3+ to Mn2+ followed by reduction of Ti4+ to Ti3+. The XAS and PES measurements give fully consistent results regarding the amount of inserted lithium.
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| 25. |
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| 26. |
- Sjöberg, Mats, 1965-, et al.
(författare)
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Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis : a retrospective observational study
- 2012
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Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 18:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Methods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n 49) treated with a single infusion of IFX; 2) an Austrian cohort (n 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. Results: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. Conclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.
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| 27. |
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| 28. |
- Syvänen, Stina, 1978-
(författare)
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Blood-Brain Barrier Transport : Investigation of Active Efflux using Positron Emission Tomography and Modelling Studies
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the transport of exogenous molecules across the blood-brain barrier (BBB), focusing on active efflux, using positron emission tomography (PET), computer simulation and modelling. P-glycoprotein (P-gp) inhibition was studied using [11C]verapamil and [11C]hydroxyurea was investigated as a new marker for active efflux transport. Simulations were carried out to explore the importance of the efflux transporter location in the BBB. Brain concentrations of [11C]verapamil, [11C]GR205171 and [18F]altanserin were compared in various laboratory animal species and in humans.A central aspect of the studies has been the novel combination of dynamic PET imaging of the brain pharmacokinetics of a labelled drug, administered through an exponential infusion scheme allowing time-resolved consequence analysis of P-gp inhibition, and mathematical modelling of the obtained data. The methods are applicable to drugs under development and can be used not only in rodents but also in higher species, potentially even in humans, to investigate the effects of P-gp or other transporters on drug uptake in the brain.The inhibition of P-gp by cyclosporin A (CsA) and the subsequent change in brain concentrations of [11C]verapamil occurred rapidly in the sense that [11C]verapamil uptake increased rapidly after CsA administration but also in the sense that the increased uptake was rapidly reversible. The P-gp inhibition was best described by an inhibitory indirect effect model in which CsA decreased the transport of [11C]verapamil out of the brain. The model indicated that approximately 90% of the transport of [11C]verapamil was P-gp-mediated. The low brain concentrations of [11C]hydroxyurea appeared to be a result of slow transport across the BBB rather than active efflux. This exemplifies why the extent and the rate of brain uptake should be approached as two separate phenomena. The brain-to-plasma concentration ratios for the three studied radiotracers differed about 10-fold be-tween species, with lower concentrations in rodents than in humans, monkeys and pigs. The increase in brain concentrations after P-gp inhibition was somewhat greater in rats than in the other species.The findings demonstrate a need to include the dynamics of efflux inhibition in the experimental design and stress the importance of the choice of species in preclinical studies of new drug candidates.
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| 29. |
- Syvänen, Stina, et al.
(författare)
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Duration and degree of cyclosporin induced P-glycoprotein inhibition in the rat blood-brain barrier can be studied with PET
- 2006
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 32:3, s. 1134-1141
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Tidskriftsartikel (refereegranskat)abstract
- Active efflux transporters in the blood-brain barrier lower the brain concentrations of many drug molecules and endogenous substances and thus affect their central action. The objective of this investigation was to study the dynamics of the entire inhibition process of the efflux transporter P-glycoprotein (P-gp), using positron emission tomography (PET). The P-gp marker [C-11]verapamil was administered to anesthetized rats as an i.v. bolus dose followed by graded infusions via a computerized pump system to obtain a steady-state concentration of [C-11]verapamil in brain. The P-gp modulator cyclosporin A (CsA) (3, 10 and 25 mg/kg) was administered as a short bolus injection 30 min after the start of the [C-11]verapamil infusion. The CsA pharmacokinetics was studied in whole blood in a parallel group of rats. The CsA blood concentrations were used as input to model P-gp inhibition. The inhibition of P-gp was observed as a rapid increase in brain concentrations of [C-11]verapamil, with a maximum after 5, 7.5 and 17.5 min for the respective doses. The respective increases in maximal [C-11]verapamil concentrations were 1.5, 2.5 and 4 times the baseline concentration. A model in which CsA inhibited P-gp by decreasing the transport of [C-11]verapamil out from the brain resulted in the best fit. Our data suggest that it is not the CsA concentration in blood, but rather the CsA concentration in an effect compartment, probably the endothelial cells of the blood-brain barrier that is responsible for the inhibition of P-gp.
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| 30. |
- Syvänen, Stina, et al.
(författare)
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PET-evaluated transport of [11C]hydroxyurea across the rat blood-brain barrier - : lack of influence of cyc-losporin and probenecid
- 2007
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Ingår i: Drug Metabolism Letters. - : Bentham Science Publishers Ltd.. - 1872-3128. ; 1:3, s. 189-194
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Tidskriftsartikel (refereegranskat)abstract
- The transport of hydroxyurea, a ribonucleoside reductase inhibitor, over biological membranes is slow and it has therefore been suggested that the substance could interact with an active efflux transporter. The transport of [11C]hydroxyurea into the rat brain was therefore studied after administration of the multidrug resistance protein inhibitor probenecid (50 and 150 mg/kg), the P-glycoprotein inhibitor cyclosporin A (25 mg/kg), hydroxyurea (50, 150 and 450 mg/kg) and mannitol (25%). None of the intervention drugs affected the brain uptake of [11C]hydroxyurea. The brain-toplasma concentration ratios (Kp), with or without intervention drug, were in the range 0.12-0.25 after 60 min of [11C]hydroxyurea infusion. [11C]Verapamil, a P-glycoprotein substrate with low brain penetration, was used to study the ability of hydroxyurea to inhibit P-glycoprotein. Administration of hydroxyurea (150 and 450 mg/kg) did not increase brain concentrations of [11C]verapamil. It is therefore unlikely that hydroxyurea is a substrate for or an inhibitor of Pglycoprotein or a substrate for a probenecid sensitive transport system. The low brain concentrations may instead be the result of slow uptake due to the hydrophilic nature of hydroxyurea.
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| 31. |
- Syvänen, Stina, et al.
(författare)
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Pharmacokinetics of P-glycoprotein inhibition in the rat blood-brain barrier
- 2008
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 97:12, s. 5386-5400
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Tidskriftsartikel (refereegranskat)abstract
- This article describes the experimental set-up and pharmacokinetic modeling of P-glycoprotein function in the rat blood-brain barrier using [(11)C]verapamil as the substrate and cyclosporin A as an inhibitor of P-gp. [(11)C]verapamil was administered to rats as an i.v. bolus dose followed by graded infusions to obtain steady-state concentrations in the brain during 70 min. CsA was administered as a bolus followed by a constant infusion 20 min after the start of the [(11)C]verapamil infusion. The brain uptake of [(11)C]verapamil over 2 h was portrayed in a sequence of PET scans in parallel with measurement of [(11)C]verapamil concentrations in blood and plasma and CsA concentrations in blood. Mixed effects modeling in NONMEM was used to build a pharmacokinetic model of CsA-induced P-gp inhibition. The brain pharmacokinetics of [(11)C]verapamil was well described by a two-compartment model. The effect of CsA on the uptake of [(11)C]verapamil in the brain was best described by an inhibitory indirect effect model with an effect on the transport of [(11)C]verapamil out of the brain. The CsA concentration required to obtain 50% of the maximal inhibition was 4.9 microg/mL (4.1 microM). The model parameters indicated that 93% of the outward transport of [(11)C]verapamil was P-gp mediated.
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| 32. |
- Syvänen, Stina, et al.
(författare)
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Predicting brain concentrations of drug using positron emission tomography and venous input : modeling of arterial-venous concentration differences
- 2006
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 62:10, s. 839-848
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEIn a positron emission tomography (PET) study, the concentrations of the labeled drug (radiotracer) are often different in arterial and venous plasma, especially immediately following administration. In a PET study, the transfer of the drug from plasma to brain is usually described using arterial plasma concentrations, whereas venous sampling is standard in clinical pharmacokinetic studies of new drug candidates. The purpose of the study was to demonstrate the modeling of brain drug kinetics based on PET data in combination with venous blood sampling and an arterio-venous transform (T(av)).METHODSBrain kinetics (C(br)) was described as the convolution of arterial plasma kinetics (C(ar)) with an arterial-to-brain impulse response function (T(br)). The arterial plasma kinetics was obtained as venous plasma kinetics (C(ve)) convolved with the inverse of the arterio-venous transform (T(av) (-1)). The brain kinetics was then given by C(br)=C(ve)*T(av) (-1)*T(br). This concept was applied on data from a clinical PET study in which both arterial and venous plasma sampling was done in parallel to PET measurement of brain drug kinetics. The predictions of the brain kinetics based on an arterial input were compared with predictions using a venous input with and without an arterio-venous transform.RESULTSThe venous based models for brain distribution, including a biexponential arterio-venous transform, performed comparably to models based on arterial data and better than venous based models without the transform. It was also shown that three different brain regions with different shaped concentration curves could be modeled with a common arterio-venous transform together with an individual brain distribution model.CONCLUSIONWe demonstrated the feasibility of modeling brain drug kinetics based on PET data in combination with venous blood sampling and an arterio-venous transform. Such a model can in turn be used for the calculation of brain kinetics resulting from an arbitrary administration mode by applying this model on venous plasma pharmacokinetics. This would be an important advantage in the development of drugs acting in the brain, and in other circumstances when the effect is likely to be closer related to the brain than the plasma concentration.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Waldo, Åsa, et al.
(författare)
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Local attitudes towards management measures for the co-existence of seals and coastal fishery - A Swedish case study
- 2020
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Ingår i: Marine Policy. - : Elsevier BV. - 0308-597X. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Marine mammals and coastal fisheries are two features commonly associated with thriving marine environments, but it is also a case of wildlife impact on human interests. This paper analyses the seal-fisheries encounter in a Swedish Baltic Sea fishery. The problem concerns seals eating fish from the fishing gear which causes considerable economic losses to small-scale fishermen. This mixed-method study addresses local attitudes towards management measures that might be introduced. A questionnaire was sent to all households in three traditional fishing villages and interviews were conducted with local stakeholders. The results show a consensus that something needs to be done or the local fishery cannot continue. Economic compensation for lost catches is viewed as a short-term strategy, while investment subsidies for seal-proof gear are considered positive but problematic due to low efficiency of the new gear. The management measure viewed as most positive in the local context is hunting. In general, a more active management is perceived as urgent for the survival of the small-scale coastal fishery in the studied area.
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