| 148511. |
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| 148512. |
- Lindqvist, Aron, 1964-, et al.
(författare)
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DASH and Sollerman test scores after hand injury from powered wood splitters
- 2011
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Ingår i: Journal of Hand Surgery, European Volume. - : SAGE Publications. - 1753-1934 .- 2043-6289. ; 36E:1, s. 57-61
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the study was to describe the outcome after hand injury from powered wood splitters, and to investigate the relation between injury severity and outcome. Injury severity was rated according to the Hand Injury Severity Scoring System (HISS system) and the Injury Severity Score method. The patients were evaluated with the Disabilities of the Arm Shoulder and Hand outcome questionnaire (DASH), and 26 of the most severely injured patients were evaluated with the Sollerman test. The mean DASH score was moderately elevated at 15, indicating that many of these patients have sequelae. A statistically significant correlation between HISS and DASH scores was found, implying that initial injury severity is of importance for outcome. The mean Sollerman score in the injured hand was 66, which amounts to a significantly impaired hand function.
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| 148513. |
- Lindqvist, Annika, et al.
(författare)
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Enhanced Brain Delivery of the Opioid Peptide DAMGO in Glutathione PEGylated Liposomes : A Microdialysis Study
- 2013
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 10:5, s. 1533-1541
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Tidskriftsartikel (refereegranskat)abstract
- Glutathione PEGylated (GSH-PEG) liposomes were evaluated for their ability to enhance and prolong blood-to-brain drug delivery of the opioid peptide DAMGO (H-Tyr-d-Ala-Gly-MePhe-Gly-ol). An intravenous loading dose of DAMGO followed by a 2 h constant rate infusion was administered to rats, and after a washout period of 1 h, GSH-PEG liposomal DAMGO was administered using a similar dosing regimen. DAMGO and GSH-PEG liposomal DAMGO were also administered as a 10 min infusion to compare the disposition of the two formulations. Microdialysis made it possible to determine free DAMGO in brain and plasma, while the GSH-PEG liposomal encapsulated DAMGO was measured with regular plasma sampling. The antinociceptive effect of DAMGO was determined with the tail-flick method. All samples were analyzed using liquid chromatography–tandem mass spectrometry. The short infusion of DAMGO resulted in a fast decline of the peptide concentration in plasma with a half-life of 9.2 ± 2.1 min. Encapsulation in GSH-PEG liposomes prolonged the half-life to 6.9 ± 2.3 h. Free DAMGO entered the brain to a limited extent with a steady state ratio between unbound drug concentrations in brain interstitial fluid and in blood (Kp,uu) of 0.09 ± 0.04. GSH-PEG liposomes significantly increased the brain exposure of DAMGO to a Kp,uu of 0.21 ± 0.17 (p < 0.05). By monitoring the released, active substance in both blood and brain interstitial fluid over time, we were able to demonstrate that GSH-PEG liposomes offer a promising platform for enhancing and prolonging the delivery of drugs to the brain.
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| 148514. |
- Lindqvist, Annika, 1983-, et al.
(författare)
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Exploring Factors Causing Low Brain penetration of the Opioid Peptide DAMGO through Experimental Methods and Modeling
- 2016
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:4, s. 1258-1266
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Tidskriftsartikel (refereegranskat)abstract
- To advance the development of peptide analogues for improved treatment of pain, we need to learn more about the blood brain barrier transport of these substances. A low penetration into the brain, with an unbound brain to blood ratio, K-p,K-uu, of 0.08, is an important reason for the lack of effect of the enkephalin analogue DAMGO (H-Tyr-D-Ala-Gly-MePhe-Gly-ol) according to earlier findings. The aim of this study was to investigate the role of efflux transporters, metabolism in the brain, and/or elimination through interstitial fluid bulk flow for the brain exposure of DAMGO. The in vivo brain distribution of DAMGO was evaluated using microdialysis in the rat. Data were analyzed with population modeling which resulted in a clearance into the brain of 1.1 and an efflux clearance 14 mu L/min/g_brain. The efflux clearance was thus much higher than the bulk flow known from the literature. Coadministration with the efflux transporter inhibitors cyclosporin A and elacridar in vivo did not affect K-p,K-uu. The permeability of DAMGO in the Caco-2 assay was very low, of the same size as mannitol. The efflux ratio was <2 and not influenced by cyclosporin A or elacridar. These results indicate that the well-known efflux transporters Pgp and Bcrp are not responsible for the higher efflux of DAMGO, which opens up for an important role of other transporters at the BBB.
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| 148515. |
- Lindqvist, Aron, et al.
(författare)
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Hand injury from powered wood splitters : machine safety, patterns of use and injury events.
- 2011
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Ingår i: International Journal of Occupational Safety and Ergonomics. - 1080-3548 .- 2376-9130. ; 17:2, s. 175-86
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The purpose of this study was to describe factors of possible importance for the occurrence of hand injury from powered wood splitters.PATIENTS: Patients were identified by a computerized patient registry. Information was obtained from hospital records, a written questionnaire and a structured telephone interview.RESULTS: Very few splitters were constructed according to European standards. Twenty-one percent of patients injured with wedge splitters thought that having more than one person at the machine was one cause of the accident. Seventy-nine percent of patients injured with screw splitters stated that glove use was one cause of the accident.CONCLUSIONS: The level of safety in wood splitters that cause hand injury is often poor. Having more than one person at the machine during work may contribute to wedge splitter injury. Glove use commonly contributes to screw splitter injury. Prevention should be directed towards unsafe machines and dangerous patterns of use.
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| 148516. |
- Lindqvist, Aron, et al.
(författare)
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Hand injury from powered wood splitters
- 2008
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 0284-4311 .- 1651-2073. ; 42:5, s. 246-52
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Tidskriftsartikel (refereegranskat)abstract
- We describe the types of hand injury sustained from powered wood splitters. Information about all patients with such injuries treated at the Department of Hand Surgery, University Hospital, Uppsala, during the period 1995-2001 was collected from their records, and from written questionnaires and telephone interviews. Fourteen of the 131 patients found were below the age of 15. There was no change in the annual injury rate for inpatients. Wedge splitters caused 82% and screw splitters 18% of all injuries. The part of the hand most often injured by screw splitters was the metacarpus and by wedge splitters the index finger. Screw splitters caused palmar perforation, avulsion of the thumb, and shredding injuries. Traumatic amputation and devascularising injuries were also common. Hand injury from powered wood splitters is an important and continuing problem. Most injuries are caused by wedge splitters, injuries caused by screw splitters differ from those caused by wedge splitters. Preventive measures are needed and should include keeping children away from splitters. Further research to facilitate prevention is warranted.
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| 148517. |
- Lindqvist, Aron, 1964-
(författare)
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Hand Injury from Powered Wood Splitters
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study on hand injury from powered wood splitters was to describe injury epidemiology and anatomy, to rate injury severity, to evaluate the outcome after injury and to describe factors of possible importance for the occurrence of injury.By searching a computerized patient registry, 131 patients injured by wood splitters from 1995 to 2001 were identified. Information was obtained from hospital records and radiographs, a written questionnaire and a structured telephone interview. Injury severity was rated according to the Hand Injury Severity Scoring System (HISS system) and the Injury Severity Score (ISS). Outcome was evaluated with the Disabilities of the Arm, Shoulder and Hand outcome questionnaire (DASH) and, in 26 of the most severely injured patients, with the Sollerman test.Forty-six percent of the injuries occurred during April or May. Wedge splitters caused 82 % of all injuries and most often injured the index finger, while screw splitters caused 18 % of all injuries and most often injured the metacarpus. Screw splitters caused palmar perforation and thumb avulsion. Sixty-three percent of all patients had an amputation or devascularising injury. The reliability of HISS rating was good. The mean Hand Injury Severity Score (HISS) was 63 which is equivalent to a severe hand injury. The mean ISS was 3.7. Nineteen percent of patients had minor, 31 % had moderate, 23 % had severe and 27 % had major injury according to the HISS system. Children had more severe injuries than adults. There was no significant difference regarding HISS or DASH scores between wedge and screw splitter injuries. The mean DASH score was 15, indicating moderate residual sequelae, but patients without sequelae and patients with grave sequelae were found in all HISS severity grades. There was a weak but significant correlation between the HISS and DASH scores. The mean Sollerman score in the injured hand was 66, indicating significantly impaired hand function. Twenty-nine percent of splitters were home-made. Very few machines had the safety measures required by European Standards. Children were present during splitting in at least 15 % of cases. Not being alone at the machine was one cause of wedge splitter injury. Glove use was one cause of screw splitter injury.Hand injury from powered wood splitters is a significant problem. Many of the injuries are severe, and cause long term sequels and impairment of hand function. Prevention is essential and should focus on unsafe machines and dangerous patterns of use.
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| 148518. |
- Lindqvist, Aron, 1964-, et al.
(författare)
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Hand injury from powered wood splitters : machine safety, patterns of use and injury events
- 2011
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Ingår i: International Journal of Occupational Safety and Ergonomics. - 1080-3548 .- 2376-9130. ; 17:2, s. 175-186
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The purpose of this study was to describe factors of possible importance for the occurrence of hand injury from powered wood splitters. Patients: Patients were identified by a computerized patient registry. Information was obtained from hospital records, a written questionnaire and a structured telephone interview. Results: Very few splitters were constructed according to European Standards. Twenty-one percent of patients injured by wedge splitters thought that having more than one person at the machine was one cause of the accident. Seventy-nine percent of patients injured by screw splitters stated that glove use was one cause of the accident. Conclusions: The level of safety in wood splitters that cause hand injury is often poor. Having more than one person at the machine during work may contribute to wedge splitter injury. Glove use commonly contributes to screw splitter injury. Prevention should be directed towards unsafe machines and dangerous patterns of use.
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| 148519. |
- Lindqvist, Annika, 1983-, et al.
(författare)
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In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes
- 2016
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 33:1, s. 177-185
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:The purpose of this study was to evaluate formulation factors causing improvement in brain delivery of a small peptide after encapsulation into a targeted nanocarrier in vivo.Methods:The evaluation was performed in rats using microdialysis, which enabled continuous sampling of the released drug in both the brain (striatum) and blood. Uptake in brain could thereby be studied in terms of therapeutically active, released drug.Results:We found that encapsulation of the peptide DAMGO in fast-releasing polyethylene glycol (PEG)ylated liposomes, either with or without the specific brain targeting ligand glutathione (GSH), doubled the uptake of DAMGO into the rat brain. The increased brain delivery was observed only when the drug was encapsulated into the liposomes, thus excluding any effects of the liposomes themselves on the blood-brain barrier integrity as a possible mechanism. The addition of a GSH coating on the liposomes did not result in an additional increase in DAMGO concentrations in the brain, in contrast to earlier studies on GSH coating. This may be caused by differences in the characteristics of the encapsulated compounds and the composition of the liposome formulations. Conclusions:We were able to show that encapsulation into PEGylated liposomes of a peptide with limited brain delivery could double the drug uptake into the brain without using a specific brain targeting ligand.
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| 148520. |
- Lindqvist, Anna-Karin B.
(författare)
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The genetics of systemic lupus erythematosus : Mapping of susceptibility loci for human SLE
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is a systemic autoimmune disease affecting organs such as skin, jointsand kidneys. Characteristic for the disease is increased production of autoantibodies, in particular against dsDNA. Previous studies of SLE in mouse models and in humans indicate polygenic inheritance and genetic heterogeneity.For the purpose of genome scanning, we designed a set of chromosome specific panels of microsatellite markers for efficient genotyping. The 391 microsatellite markers, available from the Weber set 6.0 (CHLC), were organized according to chromosome and size of amplification products and were assigned fluorescent color for detection by ABI automated sequencers. The efficiency of the markers was evaluated regarding amplification of genomic DNA extracted from peripheral blood, formalin-fixed biopsy and pieces of hair. We conducted a genome wide search for SLE susceptibility loci in multi-case families from Iceland and Sweden using two-point linkage analysis. Prior to the analysis, the family material was stratified based on the presence of the deficiency of complement component C4A, a potential risk factor for susceptibility to SLE. Eighteen chromosomal regions with LOD scores > 1.0 were identified, some of which were shared between the two population groups. The most pronounced linkage was found on chromosome 2q37, with a LOD score of 4.24 in the combined family material. The locus was denoted hSLE1.To further evaluate the 2q37 region we analyzed additional microsatellite markers in families from Iceland; Sweden and Norway. The highest two-point lod score was obtained for the marker D2S125 and the multipoint analysis indicated the position of the locus between D2S125 and D2S2986 with a peak lod score of 5.29 at D2S125. No evidence of linkage was found in a set of families from Mexico. We also investigated the gene encoding interleukin 10 (IL-10) on chromosome 1, previously suggested to be a candidate gene for susceptibility to SLE. A microsatellite marker in the IL-10 promotor region was studied in 330 Mexican SLE patients and 368 ethnically matched controls for association to the disease. In addition, linkage to the same marker was evaluated in multi-case families from Iceland, Sweden and Mexico. No association or linkage was found.
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