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Sökning: WFRF:(Carlsson Margaretha S.)

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  • Hjorth, Martin, et al. (författare)
  • Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
  • 2012
  • Ingår i: European journal of haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 88:6, s. 485-496
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Objectives:  Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. Methods:  Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. Results:  After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. Conclusions:  Thalidomide (50–100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
  • Eriksson, M, et al. (författare)
  • The impact of birth weight on prostate cancer incidence and mortality in a population-based study of men born in 1913 and followed up from 50 to 85 years of age.
  • 2007
  • Ingår i: Prostate. - 0270-4137 .- 1097-0045. ; 67:11, s. 1247-1254
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Insulin-like growth factor-I (IGF-I) hormone is directly associated with birth weight (BW), and high IGF-I measured in adults is associated with increased risk of prostate cancer (PCA). Whether BW and PCA are related is inconclusive to date. METHODS BW and PCA incidence and mortality data for a population-based cohort of 1,436 singleton Swedish men born in 1913 and followed until 85 years of age were obtained. RESULTS BW 4,250 g was associated with significantly higher PCA incidence [62% (CI: 4%-151%)] and PCA mortality [82% (CI: 3%-221%)] than BW 3,001-4,249 g, even when other potential effect modifiers were taken into account. The hazards ratio for PCA incidence fell from approximately 3 at age 50 to unity at age 85. Approximately one out of every six PCA incident cases between 50 and 70 years of age could be attributed to BW 4,250 g. CONCLUSIONS In the current study PCA incidence and mortality rate appears to increase with BW. Prostate 67: 1247-1254, 2007. © 2007 Wiley-Liss, Inc.
  • Carlsson, Margaretha S. (författare)
  • Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man
  • 1993
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • 2-Mercaptopropionylglycine (2-MPG, tiopronin) has been used successfully in the treatment of cystinuria despite the lack of knowledge of its pharmacokinetics. Therefore methods based on high-performance liquid chromatography and fluorometric detection were developed for quantitative analysis. The total, non-protein-bound, and free (thiolic) tiopronin were measured in plasma using this method.The phannacokinetic disposition of tiopronin in plasma after intravenous administration was best described by a three exponential function. Plasma concentration time-curves of total tiopronin exhibited a rapid distribution phase, a B-phase corresponding to renal excretion, and a long terminal elimination phase. The latter was the result of strong disulphide binding of tiopronin to proteins. The non-protein-bound tiopronin was eliminated faster judging by its early appearance in urine. Mean bioavailability was 63 % in healthy volunteers with great interindividual variability (range 33-91%).Multiple dosing studies gave similar pharrnacokinetic parameters as for single dose studies and studies on patients with renal impaitment elucidated the renal clearance of the drug. In vitro studies showed a slow dissolution of the drug dosage form employed. A metabolite, 2-mercaptopropionic acid, was identified and its pharmacokinetics was investigated. The mechanism of action of the drug is discussed based on the results of measuring free tiopronin in plasma.
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