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- Boguszewski, M. C., et al.
(författare)
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Growth Hormone Treatment in Short Children Born Prematurely--Data from KIGS
- 2011
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:6, s. 1687-94
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Tidskriftsartikel (refereegranskat)abstract
- Context: Children born prematurely with growth failure might benefit from GH treatment. Objectives: The aim was to evaluate the first year growth response to GH treatment in short children born prematurely and to identify predictors of the growth response. Design/Patients: A total of 3215 prepubertal children born prematurely who were on GH treatment were selected from KIGS (The Pfizer International Growth Database), a large observational database. They were classified according to gestational age as preterm (PT; 33 to no more than 37 wk) and very preterm (VPT; <33 wk), and according to birth weight as appropriate for gestational age [AGA; between -2 and +2 sd score (SDS)] and small for gestational age (SGA; -2 SDS or below). Results: Four groups were identified: PT AGA (n = 1928), VPT AGA (n = 629), PT SGA (n = 519), and VPT SGA (n = 139). GH treatment was started at a median age of 7.5, 7.2, 6.7, and 6.0 yr, respectively. After the first year of GH treatment, all four groups presented a significant increase in weight gain and height velocity, with a median increase in height SDS higher than 0.6. Using multiple stepwise regression analysis, 27% of the variation in height velocity could be explained by the GH dose, GH peak during provocative test, weight and age at GH start, adjusted parental height, and birth weight SDS. The first year growth response of the children born PT and SGA could be estimated by the SGA model published previously. Conclusion: Short children born prematurely respond well to the first year of GH treatment. Long-term follow-up is needed.
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| 5. |
- Bullinger, M., et al.
(författare)
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Cross-Cultural Equivalence of the Patient- and Parent-Reported Quality of Life in Short Stature Youth (QoLISSY) Questionnaire
- 2014
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 82:1, s. 18-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Testing cross-cultural equivalence of patient-reported outcomes requires sufficiently large samples per country, which is difficult to achieve in rare endocrine paediatric conditions. We describe a novel approach to cross-cultural testing of the Quality of Life in Short Stature Youth (QoLISSY) questionnaire in five countries by sequentially taking one country out (TOCO) from the total sample and iteratively comparing the resulting psychometric performance. METHODS: Development of the QoLISSY proceeded from focus group discussions through pilot testing to field testing in 268 short-statured patients and their parents. To explore cross-cultural equivalence, the iterative TOCO technique was used to examine and compare the validity, reliability, and convergence of patient and parent responses on QoLISSY in the field test dataset, and to predict QoLISSY scores from clinical, socio-demographic and psychosocial variables. RESULTS: Validity and reliability indicators were satisfactory for each sample after iteratively omitting one country. Comparisons with the total sample revealed cross-cultural equivalence in internal consistency and construct validity for patients and parents, high inter-rater agreement and a substantial proportion of QoLISSY variance explained by predictors. CONCLUSION: The TOCO technique is a powerful method to overcome problems of country-specific testing of patient-reported outcome instruments. It provides an empirical support to QoLISSY's cross-cultural equivalence and is recommended for future research. (c) 2014 S. Karger AG, Basel.
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| 6. |
- Kvitne, K. E., et al.
(författare)
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Correlations between 4 beta-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range
- 2022
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 78:8, s. 1289-1299
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4 beta-hydroxycholesterol (4 beta OHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4 beta OHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range. Methods The patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4 beta OHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam. Results 4 beta OHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (rho = 0.53, p < 0.001), and hepatic CYP3A4 concentrations (rho = 0.30, p = 0.027), but not with intestinal CYP3A4 concentrations (rho = 0.18, p = 0.28) or intestinal microsomal CYP3A4 activity (rho = 0.15, p = 0.53). 4 beta OHC concentrations correlated weakly with midazolam absolute bioavailability (rho = - 0.23, p = 0.027) and apparent oral clearance (rho = 0.28, p = 0.008), but not with systemic clearance (rho = - 0.03, p = 0.81). Conclusion These findings suggest that 4 beta OHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4 beta OHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs.
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| 7. |
- Kvitne, K. E., et al.
(författare)
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Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial
- 2022
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Ingår i: Cts-Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 15:1, s. 221-233
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Tidskriftsartikel (refereegranskat)abstract
- It remains uncertain whether pharmacokinetic changes following Roux-en-Y gastric bypass (RYGB) can be attributed to surgery-induced gastrointestinal alterations per se and/or the subsequent weight loss. The aim was to compare short- and long-term effects of RYGB and calorie restriction on CYP3A-activity, and cross-sectionally compare CYP3A-activity with normal weight to overweight controls using midazolam as probe drug. This three-armed controlled trial included patients with severe obesity preparing for RYGB (n = 41) or diet-induced (n = 41) weight-loss, and controls (n = 18). Both weight-loss groups underwent a 3-week low-energy-diet (<1200 kcal/day) followed by a 6-week very-low-energy-diet or RYGB (both <800 kcal/day). Patients were followed for 2 years, with four pharmacokinetic investigations using semisimultaneous oral and intravenous dosing to determine changes in midazolam absolute bioavailability and clearance, within and between groups. The RYGB and diet groups showed similar weight-loss at week 9 (13 +/- 2.4% vs. 11 +/- 3.6%), but differed substantially after 2 years (-30 +/- 7.0% vs. -3.1 +/- 6.3%). At baseline, mean absolute bioavailability and clearance of midazolam were similar in the RYGB and diet groups, but higher compared with controls. On average, absolute bioavailability was unaltered at week 9, but decreased by 40 +/- 7.5% in the RYGB group and 32 +/- 6.1% in the diet group at year 2 compared with baseline, with no between-group difference. No difference in clearance was observed over time, nor between groups. In conclusion, neither RYGB per se nor weight loss impacted absolute bioavailability or clearance of midazolam short term. Long term, absolute bioavailability was similarly decreased in both groups despite different weight loss, suggesting that the recovered CYP3A-activity is not only dependent on weight-loss through RYGB.
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| 8. |
- Lindström, Björn, et al.
(författare)
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Machine Protection Experience from Beam Tests with Crab Cavity Prototypes in the CERN SPS
- 2019
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Ingår i: 10th International Particle Accelerator Conference. - : IOP Publishing.
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Konferensbidrag (refereegranskat)abstract
- Crab cavities (CCs) constitute a key component of the High Luminosity LHC (HL-LHC) project. In case of a failure, they can induce significant transverse beam offsets within tens of microseconds, necessitating a fast removal of the circulating beam to avoid damage to accelerator components due to losses from the displaced beam halo. In preparation for the final design to be employed in the LHC, a series of tests were conducted on prototype crab cavities installed in the Super Proton Synchrotron (SPS) at CERN. This paper summarizes the machine protection requirements and observations during the first tests of crab cavities with proton beams in the SPS. In addition, the machine protection implications for future SPS tests and for the use of such equipment in the HL-LHC are discussed.
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| 9. |
- Ranke, M. B., et al.
(författare)
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Major determinants of height development in Turner syndrome (TS) patients treated with GH: analysis of 987 patients from KIGS
- 2007
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Ingår i: Pediatr Res. - : Springer Science and Business Media LLC. - 0031-3998. ; 61:1, s. 105-10
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about factors determining height outcome during GH treatment in Turner syndrome (TS). We investigated 987 TS children within the Kabi International Growth Study (KIGS) who had reached near adult height (NAH) after >4 y GH treatment (including >1 y before puberty). Through multiple regression analysis we developed a model for NAH and total gain. Our results were as follows (median): 1) At start, age 9.7 yrs, height (HT) 118.0 cm (0.0 TS SDS), projected adult height 146.1 cm, GH dose 0.27 mg/kg wk; 2) NAH HT 151.0 cm (1.5 TS SDS); 3) Prepubertal gain 21.2 cm (1.6 TS SDS); 4) Pubertal gain 9.4 cm (0.0 TS SDS). NAH correlated (r = 0.67) with (ranked) HT at GH start (+), 1 year responsiveness to GH (+), MPH (+), age at puberty onset (+), age at GH start (-), and dose (+). The same factors explained (R = 0.90) the total HT gain. However, HT at GH start correlated negatively. Karyotype had no influence on outcome. Evidently, height at GH start (the taller, the better), age at GH start (the younger, the better), the responsiveness to GH (the higher, the better) and age at puberty (the later, the better) determine NAH.
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| 10. |
- Wagner, Peter, et al.
(författare)
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The policy orientation : legacy and promise
- 1991
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Die Sozialwissenschaften wurden im Laufe des 19. und zu Beginn des 20. Jahrhunderts ein Teil des Modernisierungsprozesses der westlichen Gesellschaften. Die Bezeichung Politikwissenschaft entstand nach dem zweiten Weltkrieg. Mit diesem Begriff werden die Elemente der Sozialwissenschaften bezeichnet, die sich dem Fortschritt der öffentlichen Politik (public policy) verpflichtet haben. Die Autoren stellen die Entwicklung der Politikwissenschaft der letzten vierzig Jahre dar. Den Hintergrund bilden dabei die programmatischen Thesen von H. Lasswell in "The Policy Orientation" (1951). Zu den Fragestellungen der Politikwissenschaft gehören VollbeschÀftigung, Frieden und soziale Gleichheit. Ausgehend von dieser historischen Perspektive wird ein Überblick Ìber die einzelnen Artikel des Sammelbandes gegeben. Ziel des Sammelbandes ist, eine Übersicht Ìber die unterschiedlichen Erfahrungen mit der Politikwissenschaft zu geben: Ihr historischer Kontext und ihre unterschiedliche Entwicklung in verschiedenen LÀndern soll analysiert werden. Ein erster Teil ist der Analyse der verÀnderten Relation zwischen Sozialwissenschaft und Gesellschaft gewidmet. In einem zweiten Teil wird versucht, die PrÀmissen und Praktiken der Politikwissenschaft mit neuen theoretischen Mitteln zu Ìberdenken. (ICD)
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