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| 5. |
- Edman, S., et al.
(författare)
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TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner
- 2012
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 63:3, s. 441-449
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Tidskriftsartikel (refereegranskat)abstract
- Antagonists that are sufficiently selective to preferentially block GluN2A-containing N-methyl-D-aspartate receptors (NMDARs) over GluN2B-containing NMDARs are few in number. In this study we describe a pharmacological characterization of 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl] benzyl]benzenesulphonamide (TCN 201), a sulphonamide derivative, that was recently identified from a high-throughput screen as a potential GluN2A-selective antagonist. Using two-electrode voltage-clamp (TEVC) recordings of NMDAR currents from Xenopus laevis oocytes expressing either GluN1/GluN2A or GluN1/GluN2B NMDARs we demonstrate the selective antagonism by TCN 201 of GluN2A-containing NMDARs. The degree of inhibition produced by TCN 201 is dependent on the concentration of the GluN1-site co-agonist, glycine (or D-serine), and is independent of the glutamate concentration. This GluN1 agonist-dependency is similar to that observed for a related GluN2A-selective antagonist, N-(cyclohexylmethyl)-2[{5-[(phenylmethyl)amino]-1,3,4-thiadiazol-2-yl}thio]acetamide (TCN 213). Schild analysis of TCN 201 antagonism indicates that it acts in a non-competitive manner but its equilibrium constant at GluN1/GluN2A NMDARs indicates TCN 201 is around 30-times more potent than TCN 213. In cortical neurones TCN 201 shows only modest antagonism of NMDAR-mediated currents recorded from young (DIV 9-10) neurones where GluN2B expression predominates. In older cultures (DIV 15-18) or in cultures where GluN2A subunits have been over-expressed TCN 201 gives a strong block that is negatively correlated with the degree of block produced by the GluN2B-selective antagonist, ifenprodil. Nevertheless, while TCN 201 is a potent antagonist it must be borne in mind that its ability to block GluN2A-containing NMDARs is dependent on the GluN1-agonist concentration and is limited by its low solubility. (C) 2012 Elsevier Ltd. All rights reserved.
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- Garpvall, K., et al.
(författare)
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Admission screening and cohort care decrease carbapenem resistant enterobacteriaceae in Vietnamese pediatric ICUs
- 2021
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Ingår i: Antimicrobial Resistance and Infection Control. - : BMC. - 2047-2994. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay, mortality, and costs in three Intensive Care Units (ICUs) at the Vietnamese National Childrens Hospital. Method CRE screening using rectal swabs and ChromIDCarbas elective culture at admission and if CRE negative, once weekly. Patients were treated in cohorts based on CRE colonization status. Results CRE colonization at baseline point-prevalence screening was 76.9% (103/134). Of 941 CRE screened at admission, 337 (35.8%) were CREpos. 694 patients met inclusion criteria. The 244 patients CRE negative at admission and screened > 2 times were stratified in 8 similar size groups (periods), based on time of admission. CRE acquisition decreased significant (OR - 3.2, p < 0.005) from 90% in period 2 (highest) to 48% in period 8 (last period). Patients with CRE acquisition compared to no CRE acquisition had a significantly higher rate of culture confirmed HAI, n = 20 (14%) vs. n = 2 (2%), longer hospital stays, 3.26 vs. 2.37 weeks, and higher total treatment costs, 2852 vs. 2295 USD. Conclusion Admission CRE screening and cohort care in pediatric ICUs significantly decreased CRE acquisition, cases of HAI and duration of hospital-stay.
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| 8. |
- Svedman, S., et al.
(författare)
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Longer duration of operative time enhances healing metabolites and improves patient outcome after Achilles tendon rupture surgery
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:7, s. 2011-2020
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between the duration of operative time (DOT), healing response and patient outcome has not been previously investigated. An enhanced healing response related to DOT may potentiate repair processes, especially in hypovascular and sparsely metabolized musculoskeletal tissues such as tendons. This study aimed to investigate the association between DOT and the metabolic healing response, patient-reported outcome and the rate of post-operative complications after acute Achilles tendon injury. Observational cohort, cross-sectional study with observers blinded to patient grouping. A total of two-hundred and fifty-six prospectively randomized patients (210 men, 46 women; mean age 41 years) with an acute total Achilles tendon rupture all operated on with uniform anaesthetic and surgical technique were retrospectively assessed. At 2 weeks post-operatively, six metabolites were quantified using microdialysis. At 3, 6 and 12 months, patient-reported pain, walking ability and physical activity were examined using self-reported questionnaires, Achilles tendon total rupture score, foot and ankle outcome score and physical activity scale. At 12 months, functional outcome was assessed using the heel-rise test. Complications, such as deep venous thrombosis, infections and re-operations, were recorded throughout the study. Patients who underwent longer DOT exhibited higher levels of glutamate (p = 0.026) and glycerol (p = 0.023) at 2 weeks. At the 1-year follow-up, longer DOT was associated with significantly less loss in physical activity (p = 0.003), less pain (p = 0.009), less walking limitations (p = 0.022) and better functional outcome (p = 0.014). DOT did not significantly correlate with the rate of adverse events, such as deep venous thrombosis, infections or re-ruptures. Higher glutamate levels were associated with less loss in physical activity (p = 0.017). All correlations were confirmed by multiple linear regressions taking confounding factors into consideration. The results from this study suggest a previously unknown mechanism, increased metabolic response associated with longer DOT, which may improve patient outcome after Achilles tendon rupture surgery. Allowing for a higher amount of traumatized tissue, as reflected by up-regulation of glycerol in patients with longer DOT, may prove to be an important surgical tip for stimulation of repair of hypometabolic soft tissue injuries, such as Achilles tendon ruptures.
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- Aufwerber, S, et al.
(författare)
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Changes in Tendon Elongation and Muscle Atrophy Over Time After Achilles Tendon Rupture Repair: A Prospective Cohort Study on the Effects of Early Functional Mobilization
- 2020
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Ingår i: The American journal of sports medicine. - : SAGE Publications. - 1552-3365 .- 0363-5465. ; 48:13, s. 3296-3305
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Tidskriftsartikel (refereegranskat)abstract
- Early functional mobilization (EFM) may improve patient outcome after Achilles tendon rupture (ATR). However, whether EFM affects patient outcome via changes in tendon elongation, thickening, or calf muscle atrophy is unknown.Purpose:To analyze differences in tendon and muscle morphology recovery over time between groups treated with EFM or standard treatment after ATR repair.Study Design:Cohort study; Level of evidence, 2.Methods:This prospective cohort study included 86 patients (20 women) with ATR repair who had a mean (SD) age of 39.3 (8.2) years and were part of a larger prospective randomized controlled trial. Patients were postoperatively randomized to immediate postoperative weightbearing and ankle motion (EFM group) or to immobilization in a below-knee plaster cast for 2 weeks (control group). Patient-reported and functional outcomes were assessed at 6 and 12 months with the Achilles Tendon Total Rupture Score and the heel-rise test for endurance. At 2 and 6 weeks and 6 and 12 months postoperatively, B-mode ultrasound imaging was performed to assess the length and cross-sectional area (CSA) of the Achilles tendon, the gastrocnemius CSA, as well as the thickness of soleus.Results:The Achilles Tendon Total Rupture Score for the EFM and control groups were 65.8 (18.7) and 56.8 (20.1; P = .045), respectively, at 6 months and 79.6 (15.8) and 78.9 (17.2; P = .87), respectively, at 12 months. At 2 weeks, tendon elongation was significantly more pronounced in the EFM group as compared with the control group (mean side-to-side difference, 1.88 cm vs 0.71 cm; P = .005). Subsequently, tendon elongation increased in the control group while it decreased in the EFM group so that at 6 and 12 months no significant differences between groups were found. Mean Achilles tendon elongation at 1 year was 1.73 (1.07) cm for the EFM group (n = 55) and 1.67 (0.92) cm for the control group (n = 27), with a mean difference of 0.06 cm (95% CI, 0.54 to –0.42; P = .80). Achilles tendon CSA and calf muscle atrophy displayed no significant differences between the groups; however, significant changes were demonstrated over time ( P ≤ .001) in both groups.Conclusion:EFM results in more Achilles tendon elongation at early healing, but this difference subsides over time. EFM does not seem to affect patient outcome via changes in tendon elongation, thickening, or calf muscle atrophy.Registration:NCT02318472 (ClinicalTrials.gov identifier).
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| 13. |
- Aufwerber, S, et al.
(författare)
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Does Early Functional Mobilization Affect Long-Term Outcomes After an Achilles Tendon Rupture? A Randomized Clinical Trial
- 2020
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Ingår i: Orthopaedic journal of sports medicine. - : SAGE Publications. - 2325-9671. ; 8:3, s. 2325967120906522-
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Tidskriftsartikel (refereegranskat)abstract
- Functional deficits and health-related impairments are common after an Achilles tendon rupture (ATR). Rehabilitation protocols vary greatly, and few studies have allowed loading in combination with ankle motion immediately after surgery (ie, early functional mobilization [EFM]). It is unclear whether EFM may counteract the negative impact of ankle immobilization after an ATR. Purpose: The primary aim of this study was to assess the efficacy of EFM compared with standard treatment (ie, 2 weeks of unloading in a plaster cast followed by 4 weeks of weightbearing in an orthosis) regarding patient-reported and functional outcomes in patients with an ATR after acute operative repair. The secondary aim was to explore whether the occurrence of deep venous thrombosis (DVT) during the 2 postoperative treatments affected outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 135 patients who underwent ATR repair, randomized to either EFM, including immediate postoperative loading and ankle motion, or standard treatment, were evaluated with functional tests and 5 self-administered outcome questionnaires at 6 and 12 months postoperatively. Results: At 6 months, the EFM group scored higher on the RAND 36-Item Health Survey (RAND-36) questionnaire subscales of general health and vitality ( P < .05) compared with the control group. No significant differences between the groups were found on disease-specific questionnaires (Achilles tendon Total Rupture Score [ATRS] and Foot and Ankle Outcome Score [FAOS]). At 12 months, no significant differences on any of the patient-reported outcome measures or the functional heel-rise test were seen between the groups. The RAND-36 subscale of general health, however, exhibited higher values in the EFM group (82.6 ± 16.9) than the control group (77.1 ± 17.0) ( P = .051) at 12 months after the injury. Patients sustaining DVT postoperatively had lower self-reported outcomes on the ATRS, FAOS, and RAND-36 questionnaires at 6 and 12 months compared with patients not having sustained DVT (all P < .05). Conclusion: This study demonstrated that an accelerated postoperative protocol with immediate loading and ankle motion resulted in better general health and vitality at 6 months. However, there were no differences between the groups in the recovery of heel-rise function. Future studies should focus on the means to reduce the risk of DVT to improve patient outcomes after ATR. Registration: NCT02318472 (ClinicalTrials.gov identifier).
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| 16. |
- Doeff, M.M, et al.
(författare)
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Transport properties of binary salt polymer electrolytes
- 2000
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Ingår i: Journal of Power Sources. - : Elsevier. - 0378-7753 .- 1873-2755. ; 89:2, s. 227-231
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Tidskriftsartikel (refereegranskat)abstract
- Transport properties (ionic conductivities (σ), salt diffusion coefficients (Ds), and cationic transference numbers (t+0)) as a function of salt concentration (Cs) are reported and compared for several common binary salt/polymer systems being considered for use as electrolytes in rechargeable lithium batteries for electric vehicle and other applications. The three properties provide a complete description of transport in solid polymer electrolytes (SPEs) or "dry" systems in cells undergoing galvanostatic charge and discharge. The macroscopic approach used obviates the need to know the details of speciation in these non-ideal solutions and allows for a more sophisticated correlation of the characteristics of ion transport with polymer structure, salt type, and concentration than conductivity data alone.
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| 21. |
- Edman, Maria C, et al.
(författare)
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Functional expression of the adenosine A1 receptor in rabbit lacrimal gland.
- 2008
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Ingår i: Experimental eye research. - : Elsevier BV. - 0014-4835. ; 86:1, s. 110-7
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Tidskriftsartikel (refereegranskat)abstract
- It has become increasingly clear that purine compounds play a mediator role in exocrine secretion. Therefore, the present study was aimed at examining the presence of the adenosine A1 receptor in rabbit lacrimal gland and to evaluate the role of the A1 receptor in regulated secretion. The expression of the A1 receptor was investigated with reverse transcriptase PCR, cyto- and histochemistry as well as with pharmacological methods. Acinar cells were isolated, cultured in a serum-free medium for 2 days and thereafter treated with purinergic agonists/antagonists and/or carbachol and VIP. Secretory response was assessed by measuring secreted beta-hexosaminidase enzymatic activity. Microscopical evaluation of the immunocyto- and histochemistry specimens indicated that the adenosine A1 receptor is expressed in the rabbit lacrimal gland, which was also supported by reverse transcriptase PCR resulting in a sequence 100% identical with the previously published sequence for the rabbit A1 receptor gene. Incubation of acinar cells with adenosine and the A1 specific agonist N6-cyclopentyladenosine (CPA) resulted in a fourfold increase of secretion at the determined optimal concentrations. Incubation with carbachol alone resulted in a 10- to 15-fold increase. Carbachol combined with either adenosine or CPA increased the secretion 20-fold or more, demonstrating a synergistic effect. Our data provides evidence for the presence of adenosine A1 receptors in both tissue and cultured cells. Even though adenosine and CPA alone had only a moderate effect on secretion, the observed synergistic effect with carbachol suggests a modulatory role for the adenosine A1 receptor in the lacrimal gland.
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| 24. |
- Edman-Wallér, Jon, et al.
(författare)
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Results of PCR Analysis of Mpox Clinical Samples, Sweden, 2022
- 2023
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Ingår i: Emerging Infectious Diseases. - : CENTERS DISEASE CONTROL & PREVENTION. - 1080-6040 .- 1080-6059. ; 29:6, s. 1220-1222
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Tidskriftsartikel (refereegranskat)abstract
- We compared cycle thresholds from mpox skin lesions with other specimen sites and over time from onset of clinical signs among 104 patients in Sweden. Cycle thresholds differed by anatomic site. We identified 2 ear-ly mpox cases from anorectal swab specimens after skin samples were negative, indicating necessity of sampling multiple sites.
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| 27. |
- Forsberg, M, et al.
(författare)
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No support for lipid rescue in oral poisoning: A systematic review and analysis of 160 published cases
- 2017
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Ingår i: Human & experimental toxicology. - : SAGE Publications. - 1477-0903 .- 0960-3271. ; 36:5, s. 461-466
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Tidskriftsartikel (refereegranskat)abstract
- Lipid rescue is used as treatment of various poisonings despite weak scientific evidence. Some experimental studies have indicated a positive effect, but others have not. Clinical studies are lacking, wherefore a systematic review of virtually all published human case reports is presented. The case reports were searched for in PubMed and Web of Science and examined by two experts according to an assessment form grading the probability for a causal connection between lipid rescue and improved symptoms. A total of 160 cases were finally included, of which 30 had no positive effect of lipid rescue. Among the 130 included cases with alleged positive effect, 94 were oral poisonings and 36 were cases with local anesthetic systemic toxicity (LAST). The experts’ assessment resulted in a “certain” causal connection in three cases with LAST but not in oral poisoning. Moreover, the mean assessment score among the oral poisonings was significantly worse than the corresponding score in the cases with LAST. The average log p-value of the main toxins among the oral poisonings was significantly lower than the corresponding p-value in the cases with LAST. Among the oral poisonings, 91% had received some other resuscitative treatment more or less simultaneously with lipid rescue. Considering the findings of this study and the increasingly reported adverse effects of lipid rescue, it’s reasonable to strictly limit its use in clinical practice. We would not recommend it in oral poisonings.
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| 28. |
- Fåhraeus, C, et al.
(författare)
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The K-Cl cotransporter in the lobster stretch receptor neurone-a kinetic analysis.
- 2002
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Ingår i: Journal of Theoretical Biology. - : Elsevier BV. - 1095-8541 .- 0022-5193. ; 217:3, s. 287-309
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Tidskriftsartikel (refereegranskat)abstract
- Experiments were performed to define quantitatively the substrate (K(+) and Cl(-)) dependence of the transport function (production of equally large and oppositely directed K(+)and Cl(-) flows/currents) of an earlier (Theander et al., 1999) identified electroneutral K-Cl cotransporter in the slowly adapting stretch receptor neurone of the European lobster. The experiments were based on microelectrode techniques. This allowed us to perform steady-state measurements of the so-called "instantaneous" current-voltage relationships (around a holding voltage of -65 mV after a blockage of the cell's action potential and hyperpolarization-activated currents) and intracellular ion concentrations at various settings of the extracellular K(+) and Cl(-) concentrations. From the results, we could then define steady-state values of all of the cell's non-KCl cotransporter K(+) and Cl(-) currents. Finally, the negative sums of the inferred non-KCl cotransporter K(+) and Cl(-) currents could be taken as equivalents of the K-Cl cotransporter's K(+) and Cl(-) currents for the reason that, in steady state, all membrane currents add up to zero. For the cotransporter currents, thus inferred for a range from 2.5/410.5 to 40.0/448.0 mM external K(+)/Cl(-), we found that their absolute values increased in a nonlinear fashion from about 5 nA cell(-1) at the lowest, to about 20 nA cell(-1) at the highest external K(+)/Cl(-) concentrations. Formally, this relationship could be reproduced by a Hill function-based enzyme kinetic expression simulating inward and outward transmembrane electroneutral ion transports. Following insertion of this expression into a comprehensive model of electrical membrane functions and intracellular solute and solvent control in the lobster stretch receptor neurone, the model predictions suggested that the K-Cl cotransporter does play an important role in (a) keeping intracellular Cl(-) low for a proper function of the cell's inhibitory system, and (b) enabling rapid transmembrane K(+) shifts that provide for a stabilization of the cell's membrane voltage and membrane excitability in cases of varying extracellular K(+) concentrations. The model predictions gave, however, no clear evidence that the K-Cl cotransporter is critically involved in the cell's volume regulation in conditions of varying extracellular osmolalities.
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| 37. |
- Kornalijnslijper-Altena, Renske, et al.
(författare)
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PREDIX II HER2 : Improving pre-operative systemic therapy for human epidermal growth factor receptor 2 (HER2) amplified breast cancer (BC)
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:15 Suppl.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Neo-adjuvant systemic therapy (NAT) is the standard of care for most patients with early HER2-amplified and triple negative breast cancer (BC). Increasing the rate of pathological complete response (pCR) is highly meaningful for those patients, as pCR is strongly predictive for improved long-term disease-related outcomes. Clinical and preclinical evidence support the hypothesis that pCR-rates may be augmented by the addition of checkpoint inhibitors, such as monoclonal antibodies targeting the Programmed Death Ligand receptor 1 (PD-L1), to standard systemic NAT. Studies in different BC patient cohorts (e.g., IMPassion130, PANACEA, KATE2) have indicated that PD-L1 protein expression on tumor-infiltrating lymphocytes (TIL’s) is a predictive marker for checkpoint inhibitor efficacy.Methods: We have initiated a phase II open-label, 2:1 randomized clinical trial where women with early HER2-amplified, PD-L1+ BC (cT2-3 and/or cN+) are treated with standard NAT (composed of anti-HER2 antibodies with a chemotherapy backbone of sequentially taxanes + carboplatin and epirubicin + cyclophosphamide [EC]) +/- atezolizumab during EC. N = 190 patients will be accrued in nine centers in Sweden to be able to demonstrate a 20% increase in pCR-rate, with a power of 80% and a two-sided alpha of 10%. Firstly, a prescreening is performed to select patients with a PD-L1 expression of > 1% on TIL’s. Important exclusion criteria are significant organ dysfunction and (with some exceptions) active auto-immune diseases. Extensive translational side-studies are performed to explore predictive markers for treatment efficacy, including clinicopathologic studies, molecular imaging and microbiome analyses, as well as monitoring of acute and chronic treatment-related toxicity, objective cognitive function and quality of life. As of February 11th, 4 patients have been prescreened and 1 enrolled in the trial. The clinical trial registry number is NCT03894007.
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| 38. |
- Köhler, Christian, et al.
(författare)
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Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:29
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Tidskriftsartikel (refereegranskat)abstract
- Allosteric communication within proteins is a hallmark of biochemical signaling, but the dynamic transmission pathways remain poorly characterized. We combined NMR spectroscopy and surface plasmon resonance to reveal these pathways and quantify their energetics in the glucocorticoid receptor, a transcriptional regulator controlling development, metabolism, and immune response. Our results delineate a dynamic communication network of residues linking the ligand-binding pocket to the activation function-2 interface, where helix 12, a switch for transcriptional activation, exhibits ligand- and coregulator-dependent dynamics coupled to graded activation. The allosteric free energy responds to variations in ligand structure: subtle changes gradually tune allostery while preserving the transmission pathway, whereas substitution of the entire pharmacophore leads to divergent allosteric control by apparently rewiring the communication network. Our results provide key insights that should aid in the design of mechanistically differentiated ligands.
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| 40. |
- Larsson, C., et al.
(författare)
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Factors independently related to a negative birth experience in first-time mothers
- 2011
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 2:2, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the impact of personality, socio-demographic and obstetric factors on birth experience in a cohort of healthy first-time mothers. A second aim was to compare a visual analogue scale and Wijma Delivery Experience Questionnaire B as instruments evaluating birth experience. Material and methods: In total, 541 women were prospectively followed from the end of pregnancy until 9 months postpartum. Socio-demographic, psychological and somatic data as well as personality characteristics were collected. Experience of delivery was measured with a visual analogue scale and with Wijma Delivery Experience Questionnaire B. Sixty-three variables were considered to be associated with the experience of delivery. Nineteen of these, found to be significantly associated with birth experience, were entered in a logistic regression analysis. Results: The logistic regression analysis showed that a memory of pain during birth, high usage of analgesics postpartum, long hospital stay, worry in late pregnancy and high self-rated irritation were related to a more negative birth experience, while high confidence in the midwife was related to a more positive experience. The correlation between experiences of delivery rated by Wijma Delivery Experience Questionnaire B and the visual analogue scale was 0.52 (p<0.001). Conclusion: To help women to cope with pain during and after birth could be an important factor to improve birth experience. Even though the correlation between the visual analogue scale and Wijma Delivery Experience Questionnaire B was moderate, the visual analogue scale could be used as a simple method for screening of birth experience. © 2010 Elsevier B.V.
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| 41. |
- Lindqvist, E, et al.
(författare)
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Corrigendum
- 2020
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 64:1, s. 139-139
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 42. |
- Lindqvist, E, et al.
(författare)
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Intensive care admissions due to poisoning
- 2017
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 61:10, s. 1296-1304
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Tidskriftsartikel (refereegranskat)
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