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- Lindberg, Claes, et al.
(författare)
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Liquid chromatography-tandem mass spectrometry approach for quantification of mucins from sputum using C-13,N-15-labeled peptides as internal standards
- 2013
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 1096-0309 .- 0003-2697. ; 434:1, s. 84-92
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Tidskriftsartikel (refereegranskat)abstract
- Mucins are of great interest owing their involvement in physiological and pathological processes in the airways. A method which allows accurate quantification of such proteins in sputum samples may be helpful for research in this field. A liquid chromatographic single reaction monitoring (SRM) method was developed for the quantification of two mucins, MUC5AC and MUC5B, in induced sputum samples. Sample preparation for the assay included solubilization, reduction and alkylation prior to tryptic digestion. Solid phase extraction using C(18) sorbent was used for sample clean up prior to the LC-MS/MS analysis. A cysteine containing peptide was selected for quantification of MUC5AC protein, whereas a non-cysteine peptide was used for the quantification of MUC5B protein. Stable isotope-labeled synthetic peptides were used as internal standards and linear calibration curves were constructed in the range of 0.3 - 40 pmol/L. Both mucins could be determined with a precision of 6-19% and an accuracy of 98-114%. The method is transferable to robotics and is suitable to be run in a 96-well format.
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| 2. |
- Selander, Sven-Åke, et al.
(författare)
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Olavus Petri : psalmdiktare för den goda sakens skull
- 1994
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Ingår i: Olaus Petri : den mångsidige svenske reformatorn. Nio föredrag om Olaus Petri utgivna av Cal E Hallencrfetuz och Sven-Ola Lindeberg - den mångsidige svenske reformatorn. Nio föredrag om Olaus Petri utgivna av Cal E Hallencrfetuz och Sven-Ola Lindeberg. - 0491-6786. - 9185582387 ; 49, s. 129-167
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Al-Shudifat, Abdul Rahman Mohummad, et al.
(författare)
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A Patient-Assessed Morbidity to Evaluate Outcome in Surgically Treated Vestibular Schwannomas
- 2016
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Ingår i: World Neurosurgery. - : Elsevier BV. - 1878-8750. ; 94, s. 2-550
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Outcome after treatment of vestibular schwannomas can be evaluated by health providers as mortality, recurrence, performance, and morbidity. Because mortality and recurrence are rare events, evaluation has to focus on performance and morbidity. The latter has mostly been reported by health providers. In the present study, we validate 2 new scales for patient-assessed performance and morbidity in comparison with different outcome tools, such as quality of life (QOL) (European Quality of Life-5 dimensions [EQ-5D]), facial nerve score, and work capacity.METHODS: There were 167 total patients in a retrospective (n = 90) and prospective (n = 50) cohort of surgically treated vestibular schwannomas. A new patient-assessed morbidity score (paMS), a patient-assessed Karnofsky score (paKPS), the patient-assessed QOL (EQ-5D) score, work capacity, and the House-Brackmann facial nerve score were used as outcome measures. Analysis of paMS components and their relation to other outcomes was done as uni- and multivariate analysis.RESULTS: All outcome instruments, except EQ-5D and paKPS, showed a significant decrease postoperatively. Only the facial nerve score (House-Brackmann facial nerve score) differed significantly between the retrospective and prospective cohorts. Out of the 16 components of the paMS, hearing dysfunction, tear dysfunction, balance dysfunction, and eye irritation were most often reported. Both paMS and EQ-5D correlated significantly with work capacity.CONCLUSIONS: Standard QOL and performance instruments may not be sufficiently sensitive or specific to measure outcome at the cohort level after surgical treatment of vestibular schwannomas. A morbidity score may yield more detailed information on symptoms that can be relevant for rehabilitation and occupational training after surgery.
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| 7. |
- Amble, F R, et al.
(författare)
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Amble FR, Lindberg SOH, McCaffrey TV, Runer T. Mucociliary function and endothelins 1, 2, and 3. Otolaryngol Head Neck Surg 1993;109:634-45.
- 1993
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Ingår i: Otolaryngology: Head and Neck Surgery. - 0194-5998. ; 109:4, s. 45-634
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Tidskriftsartikel (refereegranskat)abstract
- Endothelins are recently discovered peptides that cause vasoconstriction and bronchoconstriction. The significance to the mucociliary system of endothelins (ET) 1, 2 and 3 in upper as well as lower airways has not yet been clarified. Effects of these active peptides were investigated, combining both in vitro and in vivo rabbit models of mucociliary activity from the maxillary sinus and the trachea. The studies were performed using computerized photometric microscopy. Immunohistologic staining procedures were used to determine the presence of endothelins in sinus and trachea epithelium. Significant effects on mucociliary activity were noted for ET-1, -2, and -3 in vitro as well as in vivo. All endothelins were noted to accelerate mucociliary activity of both sinus and tracheal mucosa. The effects of endothelins were greater in the sinus than in the trachea. In vitro studies using the calcium blocker nifedipine and the cyclooxygenase inhibitor diclofenac indicated that the mechanism of action involves an intermediary prostaglandin pathway but is independent of release of intracellular calcium. These results were confirmed using ET-1 in vivo. Immunohistochemical staining showed endothelin to be present in both maxillary and tracheal epithelium of the rabbit. We conclude that endothelins have significant mucociliary stimulatory effects and that the presence of endothelins in normal mucosa indicates a potentially important role in respiratory homeostasis as well as inflammatory conditions.
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| 10. |
- Aranzana-Climent, Vincent, et al.
(författare)
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Translational in vitro and in vivo PKPD modelling for apramycin against Gram-negative lung pathogens to facilitate prediction of human efficacious dose in pneumonia
- 2022
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Ingår i: Clinical Microbiology and Infection. - : Elsevier B.V.. - 1198-743X .- 1469-0691. ; 28:10, s. 1367-1374
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: New drugs and methods to efficiently fight carbapenem-resistant gram-negative pathogens are sorely needed. In this study, we characterized the preclinical pharmacokinetics (PK) and pharmacodynamics of the clinical stage drug candidate apramycin in time kill and mouse lung infection models. Based on in vitro and in vivo data, we developed a mathematical model to predict human efficacy. Methods: Three pneumonia-inducing gram-negative species Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were studied. Bactericidal kinetics were evaluated with time-kill curves; in vivo PK were studied in healthy and infected mice, with sampling in plasma and epithelial lining fluid after subcutaneous administration; in vivo efficacy was measured in a neutropenic mouse pneumonia model. A pharmacokinetic-pharmacodynamic model, integrating all the data, was developed and simulations were performed. Results: Good lung penetration of apramycin in epithelial lining fluid (ELF) was shown (area under the curve (AUC)ELF/AUCplasma = 88%). Plasma clearance was 48% lower in lung infected mice compared to healthy mice. For two out of five strains studied, a delay in growth (∼5 h) was observed in vivo but not in vitro. The mathematical model enabled integration of lung PK to drive mouse PK and pharmacodynamics. Simulations predicted that 30 mg/kg of apramycin once daily would result in bacteriostasis in patients. Discussion: Apramycin is a candidate for treatment of carbapenem-resistant gram-negative pneumonia as demonstrated in an integrated modeling framework for three bacterial species. We show that mathematical modelling is a useful tool for simultaneous inclusion of multiple data sources, notably plasma and lung in vivo PK and simulation of expected scenarios in a clinical setting, notably lung infections. © 2022 The Author(s)
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