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Träfflista för sökning "WFRF:(Malmqvist Ulf) srt2:(2005-2009)"

Sökning: WFRF:(Malmqvist Ulf) > (2005-2009)

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1.
  • Pettersson, Jonas, et al. (författare)
  • Muscular exercise can cause highly pathological liver function tests in healthy men.
  • 2008
  • Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 1365-2125 .- 0306-5251. ; 65:2, s. 253-259
  • Tidskriftsartikel (refereegranskat)abstract
    • What is already known about this subject • The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. • Physical exercise can result in transient elevations of liver function tests. • There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. What this study adds • Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. • Liver function tests are significantly increased for at least 7 days after weightlifting. • It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10–12 days postexercise. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.
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2.
  • Korsgren, Magnus, et al. (författare)
  • Clinical efficacy and pharmacokinetic profiles of intranasal and oral cetirizine in a repeated allergen challenge model of allergic rhinitis.
  • 2007
  • Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 98:4, s. 316-321
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Intranasal and oral antihistamines are effective in treating allergic rhinitis. Studies comparing these routes of administration of an antihistamine regarding efficacy and pharmacokinetic profile are lacking. Objective: To compare topical and oral routes of administration of cetirizine regarding efficacy, plasma exudation, and systemic drug levels in a repeated allergen challenge model of allergic rhinitis. Methods: Oral cetirizine dihydrochloride, 10 mg once daily, and topical cetirizine dinitrate in a dose corresponding to 4.4 mg of the dihydrochloride salt twice daily were given to grass pollen-sensitive individuals for 12 days in a double-blind, placebo-controlled, crossover design. Timothy grass pollen allergen challenges were given once daily for 7 days using a nasal spray device. Nasal symptoms and peak inspiratory flow were recorded in the morning, 10 minutes after allergen challenge, and in the evening. The pharmacokinetics of the treatments was monitored in 8 patients. The remaining 28 patients were challenged topically with histamine 12 and 24 hours after the final topical and oral cetirizine doses, respectively. Nasal lavage levels of alpha(2)-macroglobulin were determined to evaluate histamine-induced mucosal plasma exudation. Results: During the last 3 days of the repeated allergen challenge model, chronic symptoms were established. Both treatments reduced symptoms 10 minutes after allergen challenge (P < .001 vs placebo). Neither treatment reduced morning and evening symptoms or nasal peak inspiratory flow. Topical, but not oral, cetirizine reduced histamine-induced plasma exudation (P < .01 vs placebo) when systemic drug levels were similar in the 2 treatment regimens. Conclusions: Topical and oral cetirizine reduced acute nasal symptoms produced by allergen challenges in patients with established chronic symptoms. There were also antihistaminic effects of topical cetirizine not related to systemic drug levels.
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3.
  • Kärrman, E, et al. (författare)
  • Assessment: environment and natural resources
  • 2006
  • Ingår i: Strategic Planning of Sustainable Urban Water Management. - 1843391058 ; , s. 22-31
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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4.
  • Mercke Odeberg, Johanna, et al. (författare)
  • UGT1A polymorphisms in a Swedish cohort and a human diversity panel, and the relation to bilirubin plasma levels in males and females
  • 2006
  • Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 62:10, s. 829-837
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The objective of this study was to investigate the prevalence of different polymorphisms and haplotypes associated with individual variations in pharmacokinetics and drug toxicity in the uridine-diphosphate glucuronosyl transferase (UGT) 1A gene in a Swedish cohort (248 healthy volunteers) and in 14 different ethnic groups. We also estimated UGT1A genotype-dependent glucuronidation efficiency using the endogenous substrate bilirubin as an indicator. Methods: Pyrosequencing-based genotyping assays were used to determine the different polymorphisms and haplotypes. Results: Haplotype analysis of the UGT1A1 (*1*28), UGT1A6 (*1*2), and UGT1A7(*1*2*3*4) allelic variants showed that three major haplotypes constituted 84% of the allelic variants in the cohort. We identified 15 haplotypes altogether from all groups, including previously undescribed haplotypes.Testing for the association of genotype and total bilirubin levels (nonfasting) in plasma disclosed that homozygous carriers of the TA allele, irrespective of haplotype combinations, had increased levels of bilirubin compared with noncarriers, but a gender-associated difference was observed. Conclusions: In a Swedish cohort, several genetic variants in the UGT1A gene are common, but prevalence in a population may differ because of ethnicity. A phenotype based on bilirubin levels has limitations in serving as an indicator of pharmacogenetic differences in glucuronidation due to the influence of gender. Because of possible substrate overlap regarding different UGT1A isoforms, determination of haplotypes of potential cis-acting polymorphisms in the UGT1A gene should be considered in pharmacogenetic association studies regarding drugs that undergo glucuronidation.
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5.
  • Norman, Elisabeth, et al. (författare)
  • Thiopental pharmacokinetics in newborn infants: a case report of overdose.
  • 2009
  • Ingår i: Acta paediatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 98, s. 1680-1682
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Thiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 mumol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10-fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available. Conclusion: Well-designed procedures and continuous education are required to prevent errors and adverse events during drug delivery to newborn infants. To develop a safe method of administration for thiopental, an extended pharmacokinetic and pharmacodynamic study in neonates is warranted.
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