| 1. |
- Abrams, Pascale, et al.
(författare)
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GH replacement in hypopituitarism improves lipid profile and quality of life independently of changes in obesity variables
- 2008
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 159:6, s. 825-832
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Tidskriftsartikel (refereegranskat)abstract
- Objective: GH deficiency (GHD) in adults is characterized by elevated body mass index (BMI), increased waist girth (WG) and increased fat mass (FM). Information about how these indicators of obesity affect the lipid profile and quality of life (QoL) of GHD subjects is scarce. It is also unclear how changes in these indicators brought about by GH replacement influence lipids and QoL. Design and methods: Adult GHD Subjects from the Pfizer International Metabolic Database were grouped according to BMI (n = 291 with BMI < 25 kg/m(2), n = 372 with BMI 25-30 kg/m(2), n = 279 with BMI > 30 kg/m(2)), WG (n = 508 with normal WG, n = 434 with increased WG) and FM (n = 357) and according to changes in these variables after 1 year of GH replacement. Serum IGF-1 concentrations, lipid concentrations and QoL using the QoL Assessment of GHD in Adults questionnaire were assessed at baseline and after 1 year of treatment. Results: At baseline, total and low-density lipoprotein (LDL) cholesterol were similarly elevated in the BMI and WG groups, but high-density lipoprotein (HDL) cholesterol decreased and triglycerides increased with increasing BMI and WG. QoL was progressively poorer with increasing BMI and WG. After 1 year of GH replacement, total and LDL cholesterol and QoL improved in all BMI, WG and FM groups. Conclusions: Variables of obesity adversely affect the already unfavourable lipid profile in GHD Subjects by decreasing HDL cholesterol, but do not counteract the positive effect of GH replacement on LDL cholesterol. Similarly, QoL is influenced by obesity, but responds equally well to GH treatment independent of BMI, WG and FM.
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| 2. |
- Abs, Roger, et al.
(författare)
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Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults - a KIMS database analysis.
- 2006
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 155:1, s. 79-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the present study was to clarify the relationship between GH deficiency (GHD) andsome cardiovascular risk factors and to analyse the effect of GH replacement therapy in a large numberof patients over a prolonged period of time.Design: Data for analysis were retrieved from KIMS (Pfizer International Metabolic Database). Serumconcentrations of total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein(LDL)-cholesterol and triglycerides were obtained from 2589 patients at baseline and from 1206patients after 1 and 2 years of GH replacement therapy. Body mass index (BMI), waist and hip, restingblood pressure and body composition were also measured.Results: At baseline, the unfavourable effects of GHD were most obvious in the lipid profiledemonstrating elevated mean total and LDL-cholesterol, in the increased waist circumference and theelevated BMI. The cholesterol concentration, BMI and body composition were significantly adverselyaffected by a number of factors, including age, sex and the use of anti-epileptic drugs. The therapeuticeffect of GH was essentially uniform across the whole population. GH replacement reduced significantlythe mean total and LDL-cholesterol, the waist circumference and the fat mass and was maintainedduring 2 years.Conclusions: This analysis of a large number of patients confirmed that GHD adults present with anincreased cardiovascular risk. The sustained improvement of the adverse lipid profile and bodycomposition suggests that GH replacement therapy may reduce the risk of cardiovascular disease andthe premature mortality seen in hypopituitary patients with untreated GHD.
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| 3. |
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| 4. |
- Abs, Roger, et al.
(författare)
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Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis
- 2013
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 168:3, s. 297-305
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Tidskriftsartikel (refereegranskat)abstract
- Objective: GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients. Design and methods: Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values < 0.05 were considered statistically significant. Results: PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04-1.23), which was significantly increased in females (1.23; 95% CI, 1.09-1.38%) but not in males (SPR 1.04; 95% CI, 0.92-1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference. Conclusions: GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures. European Journal of Endocrinology 168 297-305
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| 5. |
- Darendeliler, Feyza, et al.
(författare)
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Recurrence of brain tumours in patients treated with growth hormone: Analysis of KIGS (Pfizer International Growth Database)
- 2006
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Ingår i: ACTA PAEDIATRICA. - : Wiley. - 0803-5253. ; 95:10, s. 1284-1290
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Growth hormone (GH) has been used successfully in the treatment of short stature secondary to GH deficiency in survivors of childhood brain tumours. There has been concern that GH might increase the risk of recurrence. AIM: To analyse KIGS (Pfizer International Growth Database) with respect to tumour recurrence in patients with brain tumours. METHODS: Data for tumour recurrence were analysed retrospectively in 1038 patients with craniopharyngiomas, 655 with medulloblastomas, 113 with ependymomas, 297 with germinomas, and 400 with astrocytomas or gliomas. All patients had received recombinant human GH (Genotropin, Pfizer Inc.). RESULTS: Recurrence-free survival rates were 63% at a follow-up of 10.3 y in craniopharyngioma, 69% in 9.1 y in the glial tumours, 71% in 7.4 y in germinomas, 92% in 4.6 y in medulloblastomas and 89% in 2.5 y in ependymomas. Dose of GH and treatment modalities did not differ significantly between patients with and without recurrence. CONCLUSION: Tumour recurrence rates in surviving patients with brain tumours receiving GH treatment do not appear to be increased compared with published reports. However, longer follow-up regarding recurrences and secondary neoplasms remains essential.
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| 6. |
- Fideleff, Hugo L., et al.
(författare)
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GH deficiency during the transition period : clinical characteristics before and after GH replacement therapy in two different subgroups of patients
- 2012
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Ingår i: Journal of Pediatric Endocrinology & Metabolism (JPEM). - 0334-018X .- 2191-0251. ; 25:1-2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To study two subsets of patients with GH deficiency (GHD) during the transition period: childhood onset GHD (CO-GHD) and patients who develop GHD during the transition phase (TO-GHD) before and after GH replacement.Patients and measurements:In 1340 GHD subjects from KIMS (Pfizer International Metabolic Database), CO (n=586) or TO (n=754), background characteristics, anthropometric measurements, IGF-1, lipids and quality of life (QoL) were evaluated at baseline and after 3 years of GH replacement.Results:Both groups responded similarly to GH treatment. Changes of clinical outcomes were mainly determined by their value at baseline. Onset of the disease in childhood or transition period did not appear to be a significant predictor of response in any of the clinical outcomes.Conclusions:Age at GHD diagnosis was a significant predictor for many outcomes at baseline, but disease onset did not appear as an independent predictor concerning changes after 3 years of GH treatment. The results suggest that GH replacement during the transition period should be considered independently of the onset of the deficiency.
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| 7. |
- Höglund, Carina, et al.
(författare)
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B4C thin films for neutron detection
- 2012
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Ingår i: Journal of Applied Physics. - : American Institute of Physics (AIP). - 0021-8979 .- 1089-7550. ; 111:10
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Tidskriftsartikel (refereegranskat)abstract
- Due to the very limited availability of He-3, new kinds of neutron detectors, not based on 3He, are urgently needed. Here, we present a method to produce thin films of (B4C)-B-10, with maximized detection efficiency, intended to be part of a new generation of large area neutron detectors. B4C thin Films have been deposited onto Al-blade and Si wafer substrates by dc magnetron sputtering from (B4C)-B-nat and (B4C)-B-10 targets in an Ar discharge, using an industrial deposition system. The films were characterized with scanning electron microscopy, elastic recoil detection analysis, x-ray reflectivity, and neutron radiography. We show that the film-substrate adhesion and film purity are improved by increased substrate temperature and deposition rate. A deposition rate of 3.8 angstrom/s and substrate temperature of 400 degrees C result in films with a density close to bulk values and good adhesion to film thickness above 3 mu m. Boron-10 contents of almost 80 at. % are obtained in 6.3 m(2) of 1 mu m thick (B4C)-B-10 thin films coated on Al-blades. Initial neutron absorption measurements agree with Monte Carlo simulations and show that the layer thickness, number of layers, neutron wavelength, and amount of impurities are determining factors. The study also shows the importance of having uniform layer thicknesses over large areas, which for a full-scale detector could be in total similar to 1000 m(2) of two-side coated Al-blades with similar to 1 mu m thick (B4C)-B-10 films.
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| 10. |
- Saunois, M., et al.
(författare)
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The global methane budget 2000–2012
- 2016
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 8:2, s. 697-751
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Tidskriftsartikel (refereegranskat)abstract
- The global methane (CH4) budget is becoming an increasingly important component for managing realistic pathways to mitigate climate change. This relevance, due to a shorter atmospheric lifetime and a stronger warming potential than carbon dioxide, is challenged by the still unexplained changes of atmospheric CH4 over the past decade. Emissions and concentrations of CH4 are continuing to increase, making CH4 the second most important human-induced greenhouse gas after carbon dioxide. Two major difficulties in reducing uncertainties come from the large variety of diffusive CH4 sources that overlap geographically, and from the destruction of CH4 by the very short-lived hydroxyl radical (OH). To address these difficulties, we have established a consortium of multi-disciplinary scientists under the umbrella of the Global Carbon Project to synthesize and stimulate research on the methane cycle, and producing regular (∼ biennial) updates of the global methane budget. This consortium includes atmospheric physicists and chemists, biogeochemists of surface and marine emissions, and socio-economists who study anthropogenic emissions. Following Kirschke et al. (2013), we propose here the first version of a living review paper that integrates results of top-down studies (exploiting atmospheric observations within an atmospheric inverse-modelling framework) and bottom-up models, inventories and data-driven approaches (including process-based models for estimating land surface emissions and atmospheric chemistry, and inventories for anthropogenic emissions, data-driven extrapolations). For the 2003–2012 decade, global methane emissions are estimated by top-down inversions at 558 Tg CH4 yr−1, range 540–568. About 60 % of global emissions are anthropogenic (range 50–65 %). Since 2010, the bottom-up global emission inventories have been closer to methane emissions in the most carbon-intensive Representative Concentrations Pathway (RCP8.5) and higher than all other RCP scenarios. Bottom-up approaches suggest larger global emissions (736 Tg CH4 yr−1, range 596–884) mostly because of larger natural emissions from individual sources such as inland waters, natural wetlands and geological sources. Considering the atmospheric constraints on the top-down budget, it is likely that some of the individual emissions reported by the bottom-up approaches are overestimated, leading to too large global emissions. Latitudinal data from top-down emissions indicate a predominance of tropical emissions (∼ 64 % of the global budget, < 30° N) as compared to mid (∼ 32 %, 30–60° N) and high northern latitudes (∼ 4 %, 60–90° N). Top-down inversions consistently infer lower emissions in China (∼ 58 Tg CH4 yr−1, range 51–72, −14 %) and higher emissions in Africa (86 Tg CH4 yr−1, range 73–108, +19 %) than bottom-up values used as prior estimates. Overall, uncertainties for anthropogenic emissions appear smaller than those from natural sources, and the uncertainties on source categories appear larger for top-down inversions than for bottom-up inventories and models. The most important source of uncertainty on the methane budget is attributable to emissions from wetland and other inland waters. We show that the wetland extent could contribute 30–40 % on the estimated range for wetland emissions. Other priorities for improving the methane budget include the following: (i) the development of process-based models for inland-water emissions, (ii) the intensification of methane observations at local scale (flux measurements) to constrain bottom-up land surface models, and at regional scale (surface networks and satellites) to constrain top-down inversions, (iii) improvements in the estimation of atmospheric loss by OH, and (iv) improvements of the transport models integrated in top-down inversions. The data presented here can be downloaded from the Carbon Dioxide Information Analysis Center (http://doi.org/10.3334/CDIAC/GLOBAL_METHANE_BUDGET_2016_V1.1) and the Global Carbon Project.
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