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- Hellström, P. M., et al.
(författare)
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GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome
- 2008
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 20:6, s. 649-659
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon-like peptide-1 (GLP-1) is released after food intake to act as an incretin. GLP-1 also inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. Our aim was to study the effects of GLP-1 on gastrointestinal motility in healthy subjects and patients with irritable bowel syndrome (IBS). Antro-duodeno-jejunal manometry was carried out during a 4-h control period with saline, followed by a 4-h period with intravenous GLP-1 (healthy: 0.7 and 1.2 pmol kg-1 min-1 (n = 16), IBS, 1.2 and 2.5 pmol kg-1 min-1 (n = 14). Plasma was analysed for GLP-1 and gut hormones, and gut tissue expression of GLP-1 receptor was studied. In healthy subjects, GLP-1 0.7 pmol kg-1 min-1 reduced the migrating motor complexes (MMCs) from a median of 2 (range 2-3) to 0.5 (0-2), and motility index from 4.9 ± 0.1 to 4.3 ± 0.3 ln ∑(mmHg*s min-1) in jejunum, while GLP-1 1.2 pmol kg -1 min-1 diminshed MMCs from 2 (2-3) to 1.5 (1-2.5), and motility index from 5.2 ± 0.2 to 4.4 ± 0.2. In IBS patients, GLP-1 1.2 pmol kg-1 min-1 reduced the MMCs from 2.5 (2-3.5) to 1 (0-1.5) without affecting motility index. At 2.5 pmol kg-1 min -1 GLP-1 decreased MMCs from 2 (1.5-3) to 1 (0.5-1.5), and motility index from 5.2 ± 0.2 to 4.0 ± 0.5. Motility responses to GLP-1 were similar in antrum and duodenum. Presence of the GLP-1 receptor in the gut was verified by reverse transcriptase PCR. In conclusion, the gut peptide GLP-1 decreases motility in the antro-duodeno-jejunal region and inhibits the MMC in healthy subjects and IBS patients. © 2008 The Authors.
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- Hellström, Per M., 1954-, et al.
(författare)
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Clinical trial : The glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome
- 2009
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 29:2, s. 198-206
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype. AIMS: To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study. METHODS: Eligible patients (n = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 microg, 300 microg and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment. RESULTS: Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24%P = 0.011, 23%P = 0.005, and 12% after 300 microg, 100 microg and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients (P < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used. CONCLUSION: ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients.
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- Azzouz, H, et al.
(författare)
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Levitated droplet dye laser
- 2006
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Ingår i: Optics Express. - 1094-4087. ; 14:10, s. 4374-4379
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Tidskriftsartikel (refereegranskat)abstract
- We present the first observation, to our knowledge, of lasing from a levitated, dye droplet. The levitated droplets are created by computer controlled pico-liter dispensing into one of the nodes of a standing ultrasonic wave (100 kHz), where the droplet is trapped. The free hanging droplet forms a high quality optical resonator. Our 750 nL lasing droplets consist of Rhodamine 6G dissolved in ethylene glycol, at a concentration of 0.02 M. The droplets are optically pumped at 532 nm light from a pulsed, frequency doubled Nd:YAG laser, and the dye laser emission is analyzed by a fixed grating spectrometer. With this setup we have achieved reproducible lasing spectra in the visible wavelength range from 610 nm to 650 nm. The levitated droplet technique has previously successfully been applied for a variety of bio-analytical applications at single cell level. In combination with the lasing droplets, the capability of this high precision setup has potential applications within highly sensitive intra-cavity absorbance detection. (c) 2006 Optical Society of America.
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| 14. |
- Bilenberg, B., et al.
(författare)
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High resolution 100kV electron beam lithography in SU-8
- 2006
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317. ; 83:4-9, s. 1609-1612
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Tidskriftsartikel (refereegranskat)abstract
- High resolution 100 kV electron beam lithography in thin layers of the negative resist SU-8 is demonstrated. Sub-30 nm lines with a pitch down to 300 nm are written in 100 nm thick SU-8. Two reactive ion etch processes are developed in order to transfer the SU-8 structures into a silicon substrate, a Soft O-2-Plasma process to remove SU-8 residues on the silicon surface after development and a highly anisotropic SF6/O-2/CHF3 based process to transfer the pattern into a silicon substrate, with selectivity between silicon and SU-8 of approximately 2. 30 nm lines patterned in SU-8 are successfully transferred into a silicon substrate, which is used as a stamp in a nanoimprint lithography process to fabricate a nanochannel device for DNA stretching experiments. (c) 2006 Elsevier B.V. All rights reserved.
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| 15. |
- Ellis, M, et al.
(författare)
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Assessment of the clinical utility of serial beta-D-glucan concentrations in patients with persistent neutropenic fever
- 2008
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Ingår i: Journal of medical microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 57:3Pt 3, s. 287-295
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Tidskriftsartikel (refereegranskat)abstract
- The performance of the Fungitell assay was investigated in 100 patients with haematological malignancy undergoing chemotherapy who developed antibiotic-unresponsive neutropenic fever (AUNF). Serum β-d-glucan (BG) concentrations were significantly elevated on the first day of AUNF and all subsequent alternate days to day 10 in 38 patients who developed an invasive fungal infection (IFI) compared to 42 patients remaining free of such infections. The mean and median values of BG were 171.9±29.6 and 95.8 pg ml−1, respectively, for patients with IFI and 64.4±17.1 and 32.9 pg ml−1 for patients with only AUNF (P<0.0001). The differences remained significant over the 10 days despite antifungal therapy. The occurrence of ≥2 sequential concentrations of ≥80 pg ml−1 (‘positive’ test) was found to give the best overall option for diagnosis, with an accuracy of 81.3 %, sensitivity of 86.8 %, positive predictive value of 76.7 % and negative predictive value of 86.5 %. Of the patients with an IFI, 78 % developed a positive test at or before the clinical diagnosis was made – this occurred at a mean (range) of 1.25 (−14 to +14) days prior to the IFI diagnosis. By starting sampling of blood from the first day of neutropenia rather than from the first day of AUNF, 50 % of the patients with subsequent IFI would have been identified 5 days earlier. Increasing sampling to daily from alternate-day frequency did not further improve this earlier timing of an IFI diagnosis. A greater proportion of patients with persistent high levels of BG without overt IFI had severe enterocyte damage or mucositis than those with lower levels of BG without IFI (P=0.002). If the results of the initial BG test had been acted on to change antifungal therapy, discontinuation would have been inappropriate in 30 % of patients and would have delayed definitive antifungal therapy. Although the findings for the cohort of patients studied are very useful, there is inter-patient variability in the test's performance. An holistic diagnostic approach is therefore necessary to interpret the test results optimally. Future studies should address this in further detail as well as the impact of empirical antifungal drug use and patient outcome.
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- Graham, Ian, et al.
(författare)
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European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
- 2007
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
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Tidskriftsartikel (refereegranskat)abstract
- Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
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| 19. |
- Kellen, Eliane, et al.
(författare)
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Pooled analysis and meta-analysis of the glutathione S-transferase P1 lle 105Val polymorphism and bladder cancer: A HuGE-GSEC review
- 2007
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 165:11, s. 1221-1230
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Forskningsöversikt (refereegranskat)abstract
- The glutathione S-transferase P1 genotype (GSTP1) is involved in the inactivation of cigarette smoke carcinogens, and sequence variation in the gene may alter bladder cancer susceptibility. To examine the association between GSTP1lle 105Val and bladder cancer, the authors undertook a meta- and pooled analysis. Summary crude and adjusted odds ratios and corresponding 95% confidence intervals were pooled by using a random-effects model. In the meta-analysis (16 studies, 4,273 cases and 5,081 controls), the unadjusted summary odds ratios for GSTP1 lle/Val and Val/Val compared with GSTP1 lle/lle were 1.54 (95% confidence interval: 1.21,1.99; p < 0.001) and 2.17 (95% confidence interval: 1.27, 3.71; p = 0.005). The association appeared to be the strongest in Asian countries. When the analysis was limited to European descendents (nine studies), the summary odds ratio decreased (odds ratio = 1.24, 95% confidence interval: 1.00, 1.52) (Q = 17.50; p = 0.02). All relevant data previously contributed to the International Study on Genetic Susceptibility to Environmental Carcinogens were pooled (eight studies, 1,305 cases and 1,558 controls). The summary odds ratios were similar to the ones from the meta-analysis. Case-only analyses did not detect an interaction between the GSTP1 genotype and smoking status (never/ever). GSTP1 lle 105Val appears to be associated with a modest increase in the risk of bladder cancer.
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| 20. |
- Knot, J, et al.
(författare)
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How to set up an effective national primary angioplasty network : Lessons learned from five European countries
- 2009
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Ingår i: EuroIntervention. - 1774-024X. ; 3:299, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Percutaneous coronary interventions (PCI) are used to treat acute and chronic forms of coronary artery disease. While in chronic forms the main goal of PCI is to improve the quality of life, in acute coronary syndromes (ACS) timely PCI is a life-saving procedure - especially in the setting of ST-elevation myocardial infarction (STEMI). The aim of this study was to describe the experience of countries with successful nationwide implementation of PCI in STEMI, and to provide general recommendations for other countries. METHODS AND RESULTS: The European Association of Percutaneous Cardiovascular Interventions (EAPCI) recenty launched the Stent For Life Initiative (SFLI). The initial phase of this pan-European project was focused on the positive experience of five countries to provide the best practice examples. The Netherlands, the Czech Republic, Sweden, Denmark and Austria were visited and the logistics of ACS treatment was studied. Public campaigns improved patient access to acute PCI. Regional networks involving emergency medical services (EMS), non-PCI hospitals and PCI centres are useful in providing access to acute PCI for most patients. Direct transfer from the first medical contact site to the cathlab is essential to minimise the time delays. Cathlab staff work is organised to provide acute PCI services 24 hours a day / seven days a week (24/7). Even in those regions where thrombolysis is still used due to long transfer distances to PCI, patients should still be transferred to a PCI centre (after thrombolysis). The highest risk non-ST elevation acute myocardial infarction patients should undergo emergency coronary angiography within two hours of hospital admission, i.e. similar to STEMI patients. CONCLUSIONS: Three realistic goals for other countries were defined based on these experiences: 1) primary PCI should be used for >70% of all STEMI patients, 2) primary PCI rates should reach >600 per million inhabitants per year and 3) existing PCI centres should treat all their STEMI patients by primary PCI, i.e. should offer a 24/7 service
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- Lahermo, P, et al.
(författare)
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A quality assessment survey of SNP genotyping laboratories
- 2006
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 27:7, s. 711-714
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA) round was organized between 11 laboratories in the Nordic and Baltic countries. The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly selected SNPs. The methods used by the participating laboratories included all major platforms for small- to medium-size SNP genotyping. The laboratories used their standard procedures for SNP assay design, genotyping, and quality control. Based on the joint results from all laboratories, a consensus genotype for each DNA sample and SNP was determined by the coordinator of the survey, and the results from each laboratory were compared to this genotype. The overall genotyping accuracy achieved in the survey was excellent. Six laboratories delivered genotype data that were in full agreement with the consensus genotype. The average accuracy per SNP varied from 99.1 to 100% between the laboratories, and it was frequently 100% for the majority of the assays for which SNP genotypes were reported. Lessons from the survey are that special attention should be given to the quality of the DNA samples prior to genotyping, and that a conservative approach for calling the genotypes should be used to achieve a high accuracy.
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| 25. |
- Lange, S, et al.
(författare)
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The kinase domain of titin controls muscle gene expression and protein turnover
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 308:5728, s. 1599-1603
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Tidskriftsartikel (refereegranskat)abstract
- The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway.
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- Stein, Martin, 1976-
(författare)
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Evolution and taxonomy of Cambrian arthropods from Greenland and Sweden
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Arthropods have a rich fossil record spanning the Phanerozoic. Biomineralized forms such as the extinct trilobites are particularly common and are proven index fossils for biostratigraphy. Forms with an unmineralized cuticle are more rare, preserved only in so called konservat lagerstätten. Cambrian strata of Greenland have yielded rich trilobite faunas with potential for intercontinental correlation of Cambrian strata, but also an exceptionally preserved fauna, the Sirius Passet Lagerstätte. The first part of this thesis is concerned with trilobite biotratigraphy of the provisional Cambrian Series 2 in Greenland. The second part is concerned with exceptionally preserved arthropods from the Sirius Passet Lagerstätte, but also from 'Orsten' deposits from the Cambrian of Sweden. Perissopyge phenax occurs in the Henson Gletscher and Paralleldal formations spanning the Series 2 and 3 boundary interval in North Greenland. It also occurs in the Sekwi Formation of Yukon Territory, demonstrating that the species may hold potential for correlation within Laurentia. An indeterminate species of Perissopyge is shown to occur in the Ella Island Formation of North-East Greenland together with Olenellus cf. hanseni, which is similar to Olenellus cf. truemani described from the Henson Gletscher Formation. If this correlation is further corroborated it would offer a first tie-point for the An t'Sron Formation of North-West Scotland which yields Fritzolenellus lapworthi, herein reported for the first time from the Bastion Formation which underlies the Ella Island Formation. Oelandocaris oelandica from ‘Orsten’ deposits in the Cambrian series 3 and 4 boundary interval in Sweden is an early representative of the Crustacean stem lineage. Kiisortoqia avannaarsuensis is a new arthropod from the Sirius Passet Lagerstätte with robust antennulae strikingly similar to the 'raptorial' limb of the problematic anomalocaridids. The ventral morphology of the 'bivalved' Isoxys volucris is described for the first time and compared with other species assigned to Isoxys from Cambrian lagerstätten around the world. Finally, Siriocaris trolla, is a new arthropod that similarities with trilobites and certain ‘trilobitomorphs’ but seems to lack important synapomorphies of these taxa, though this may be due to preservational limitations in the material at hand.
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