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- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
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Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
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| 2. |
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| 3. |
- Andersson, Björn, 1977, et al.
(författare)
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Decrease in adiponectin levels correlates to growth response in growth hormone-treated children.
- 2009
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Ingår i: Hormone research. - : S. Karger AG. - 1423-0046 .- 0301-0163. ; 71:4, s. 213-8
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Tidskriftsartikel (refereegranskat)abstract
- Adiponectin is secreted by adipose tissue and circulates in human plasma at high levels. Decreased adiponectin levels are associated with insulin resistance and obesity. The aim of this study was to investigate whether changes in serum adiponectin levels are related to the growth response, insulin levels and insulin resistance during growth hormone (GH) treatment.
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| 4. |
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| 5. |
- Dahlgren, Jovanna, 1964, et al.
(författare)
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Models predicting the growth response to growth hormone treatment in short children independent of GH status, birth size and gestational age
- 2007
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Ingår i: BMC Med Inform Decis Mak. - : Springer Science and Business Media LLC. - 1472-6947. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mathematical models can be used to predict individual growth responses to growth hormone (GH) therapy. The aim of this study was to construct and validate high-precision models to predict the growth response to GH treatment of short children, independent of their GH status, birth size and gestational age. As the GH doses are included, these models can be used to individualize treatment. METHODS: Growth data from 415 short prepubertal children were used to construct models for predicting the growth response during the first years of GH therapy. The performance of the models was validated with data from a separate cohort of 112 children using the same inclusion criteria. RESULTS: Using only auxological data, the model had a standard error of the residuals (SDres), of 0.23 SDS. The model was improved when endocrine data (GHmax profile, IGF-I and leptin) collected before starting GH treatment were included. Inclusion of these data resulted in a decrease of the SDres to 0.15 SDS (corresponding to 1.1 cm in a 3-year-old child and 1.6 cm in a 7-year old). Validation of these models with a separate cohort, showed similar SDres for both types of models. Preterm children were not included in the Model group, but predictions for this group were within the expected range. CONCLUSION: These prediction models can with high accuracy be used to identify short children who will benefit from GH treatment. They are clinically useful as they are constructed using data from short children with a broad range of GH secretory status, birth size and gestational age.
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| 6. |
- Decker, Ralph, 1968, et al.
(författare)
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Different thresholds of metabolic GH effects in prepubertal children
- 2009
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Ingår i: Hormone Research.
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Konferensbidrag (refereegranskat)abstract
- Context: In addition to growth hormone (GH) effects to promote linear growth in children, GH also has substantial effects on insulin sensitivity, lipolysis, lipids, and body composition. A dissociation between anabolic and lipolytic GH effects has been suggested. Objective: The objective of the present study was to further investigate dissociated GH effects by calculating the GH doses to attain half of a given metabolic effect, the effective dose 50% (ED50%). Hypothesis: The hypothesis was that there are dose-dependent thresholds in different variables reflecting metabolism. Design: A randomized, prospective, multicentre trial was performed for a 2 years period, with two treatment regimens in short prepubertal GHD and ISS children a) individualized GH dose with six different dose groups ranging 17-100 g/kg/day (n=87) and b) fixed GH dose of 43 g/kg/day (n=41). Results: Contrary to changes in fat mass, leptin, lipids and skinfold measurements, there was evidence for different thresholds in metabolic variables for a given GH dose when performing ANOVA, p<0.001. was calculated as the difference between 2 years and start of GH treatment. Besides height (SDS), growth related variables like weight SDS and BMI (kg/m ); measures of body composition such as fat-free mass (FFM) (kg), FFM index (FFMI) (kg/m ), waist (cm), hip (cm); as well as biochemical markers like IGF-1 (SDS), IGFBP-3 (SDS); insulin (mU/L) showed dose-dependency with different ED50% levels. Conclusions: Differences of the ED50% on metabolic variables were seen in-between different GH dose spans. Thus we propose that there are different thresholds in GH effects on variables reflecting different metabolic aspects, suggesting muscle tissue being more sensitive than linear growth, GH induced insulin resistance, the rise in IGF-1 and the increase in hip circumference as a measure of 3-dimensional body growth.
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| 7. |
- Decker, Ralph, 1968, et al.
(författare)
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Individualized GH treatment gives improved growth but not higher insulin nor IGF1 compared to standard GH dose after 2 years of catch-up growth
- 2007
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Ingår i: Hormone Research. - 3805583273 ; 68:Supplement Issue 1
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Konferensbidrag (refereegranskat)abstract
- Weight-based approaches for ‘standard’ GH dosing result in dramatic variability in height outcome and IGF-1 levels. In a recent study we showed that growth response variability can be reduced by individualized GH dosing guided by the individual responsiveness estimated by our prediction model. The hypothesis was that despite many individuals needed higher GH doses, the individualized GH regimen would not give higher levels of metabolic variables compared to the group of children receiving standard treatment. We performed an open, prospective, randomized, multicentre trial in 128 prepubertal short children diagnosed as GHD or ISS, for a 2 yr catch-up growth period, with two treatment regimens providing the same mean GH dose a) individualized GH dose, ranging 17-100 µg/kg/day (n=87) and b) standard GH dose: 43 µg/kg/day (n=41). The set goal for treatment effect was to reach midparental height (MPH) SDS after 2 yrs of GH treatment. This goal was reached for a higher proportion of children treated with the individualized dose (p<0.01). Despite this there were no differences between the individual and the standard dose group concerning the mean and variances of Δinsulin, Δleptin, ΔIGF1(SDS), ΔIGF-BP3(SDS) and ΔIGF1/IGF-BP3(SDS). Δ is calculated as the difference between the value at 2 yrs and at the start of treatment. Moreover there were no differences between the groups regarding the mean or the range of these variables at 2 yrs of treatment. It can be concluded that despite a much broader range in GH dose, which comprised a maximum dose of more than 200% of the standard dose, the variability of the metabolic parameters during treatment within the groups and the absolute levels reached at 2 yrs were the same in the two groups. In fact a better growth response in relation to MPH(SDS) was achieved without a difference in metabolic variables between the groups. Individual dosing is preferable in GH treatment.
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| 8. |
- Decker, Ralph, 1968, et al.
(författare)
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Lipolytic and anabolic effects of GH are dissociated during individualized GH treatment
- 2008
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Ingår i: European Society for Paediatric Endocrinology. - 9783805586207 ; 70:Supplement Issue 1
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Konferensbidrag (refereegranskat)abstract
- Context: There is a broad variation in longitudinal growth response during GH treatment among prepubertal children. Yet, growth is but one of the several effects of GH. Our working hypothesis was a dissociation of anabolic and lipolytic effects of GH. Objective: To investigate whether diverse metabolic functions respond analogical to growth. Design: A randomized, prospective, multicentre trial was performed, for a 2 years period, with two treatment regimens providing the same mean GH dose a) individualized GH dose, six different dose groups ranging 17-100 µg/kg/day (n=87) and b) standard GH dose: 43 µg/kg/day (n=41). Patients: 128 prepubertal short children, 75% of them diagnosed as GH deficient and 25% as idiopathic short stature. Main Outcome Measures: Changes in metabolic variables (delta 2 years - start). Results: Changes in IGF-1 correlated to height gain (r=0.54, p<0.0001). Stepwise regression showed that 71% of the variation in IGF-1 was explained by height gain (49%), chnages in insulin (9%), free fat mass (FFM) (5%), and biceps skinfold (4%), as well as GH dose (4%). Changes in IGF-1 solely accounted for all changes in FFM (31%). In contrast to total fat mass, changes in FFM were significantly higher after 2 years of GH doses above 40 µg/kg/day (p<0.001 Mann-Whitney test). In principle component analysis it can be demonstrated that the anabolic variables IGF-1, IGFBP-3, FFM, and insulin target in the same direction as height gain. All variables in this vector bundle show high reciprocal partial regressions. The anabolic component is dose-dependent. Variables derived from adipose tissue (total fat mass, leptin, skin fold measurements, triglycerides) and lipid metabolism (cholesterol, HDL, LDL, triglycerides, lipoprotein(a), apolipoprotein A-II) form up a lipolytic bundle. This is unrelated to the anabolic component and dose-independent. Conclusions: This study suggests that lipolytic and anabolic effects of GH are dissociated. The threshold of GH's lipolytic effects is much lower than its anabolic and growth effects.
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| 10. |
- Forsner, Maria
(författare)
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Att vara barn i sjukdom och sjukvård : barns berättelser om sina upplevelser av sjukdom och sjukvårdsrädsla
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overarching aim of this thesis is to illuminate the experience of illness and the meaning of fear of medical care through children’s narratives. A purposive sample of 22 children and youths, aged from 2 to 18 years, narrated through play and conversation their experiences of illness and of their fear of contact with medical care. The data were analysed using thematic qualitative content analysis and the phenomenological hermeneutic method. In childhood, the experience of being ill seems to vary with the child’s age. At the ages of 7 to 10 years, the child’s way of thinking can colour the experience;imagination can produce both problems and opportunities. Children seem to combine imagination and reality, and contrasts in the experience coexist such as being scared/confident, sad/cosy and hurt/having fun. At the age of 11 to 18,being ill seemed to imply being lost, hurt and in need of comfort from themselves and others. Medical care can be frightening to children and what is fearful can differ with age. To a 2-year-old child, medical care seemed to be dangerous; to children aged 7 to 11 years, it seemed threatening, like a monster. To the 2-year-old child, there seemed to be a conflict between, on the one hand, living up to expectations by ‘being good’ and hiding their feelings or, on the other hand, communicating their fear. The narrations by children in the 7–11 year age group, point to the importance of empathy when caring for children, i.e., to be receptive of the child’s fear in order to help the child through and out of the fear. To be afraid for a two-yearold was to have one’s trust broken yet still be searching for a trustful relationship. However, if the child is received along with the fear, this opened up an opportunity for the child to develop courage and to gain control over the fear when under gentle care. The results of this research revealed the possibility of using play to create stories in a creative relationship with the child. To express one’s inner feeling is a gift of trust, a gift of hospitality. Thus when caring for children we can be the ones who are receiving that gift. We can accept the offer of being a guest in the child’s world.
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