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Träfflista för sökning "WFRF:(Christiansen Jens Sandahl) "

Sökning: WFRF:(Christiansen Jens Sandahl)

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1.
  • Allen, David B, et al. (författare)
  • GH Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
  • 2016
  • Ingår i: European Journal of Endocrinology. - 1479-683X. ; 174:2, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant human growth hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety including; cancer risk, impact on glucose homeostasis and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk and the need for longterm surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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2.
  • Berryman, Darlene E, et al. (författare)
  • Role of the GH/IGF-1 axis in lifespan and healthspan: Lessons from animal models.
  • 2008
  • Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 18:6, s. 455-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the manipulation of the GH/IGF axis influences lifespan, highlight the invertebrate and vertebrate animal models with altered lifespan due to modifications to the GH/IGF-1 signaling cascade or homologous pathways, and discuss the basic phenotypic characteristics and healthspan of these models.
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3.
  • Ceriello, Antonio, et al. (författare)
  • Diabetes as a case study of chronic disease management with a personalized approach: The role of a structured feedback loop
  • 2012
  • Ingår i: Diabetes Research and Clinical Practice. - : Elsevier. - 0168-8227 .- 1872-8227. ; 98:1, s. 5-10
  • Forskningsöversikt (refereegranskat)abstract
    • As non-communicable or chronic diseases are a growing threat to human health and economic growth, political stakeholders are aiming to identify options for improved response to the challenges of prevention and management of non-communicable diseases. This paper is intended to contribute ideas on personalized chronic disease management which are based on experience with one major chronic disease, namely diabetes mellitus. less thanbrgreater than less thanbrgreater thanDiabetes provides a pertinent case of chronic disease management with a particular focus on patient self-management. Despite advances in diabetes therapy, many people with diabetes still fail to achieve treatment targets thus remaining at risk of complications. Personalizing the management of diabetes according to the patients individual profile can help in improving therapy adherence and treatment outcomes. This paper suggests using a six-step cycle for personalized diabetes (self-)management and collaborative use of structured blood glucose data. E-health solutions can be used to improve process efficiencies and allow remote access. Decision support tools and algorithms can help doctors in making therapeutic decisions based on individual patient profiles. Available evidence about the effectiveness of the cycles constituting elements justifies expectations that the diabetes management cycle as a whole can generate medical and economic benefit.
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4.
  • Ekman, Bertil (författare)
  • IGF-I in growth hormone deficiency and in type 1 diabetes
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Both GH-deficiency and type 1 diabetes are associated with low IGF-I levels. The aim with our studies was to develop a dose titration model to obtain physiological IGF-I levels in growth hormone deficiency and to evaluate the relationship between glycaemic control and IGF-I in diabetes. First we established reference values for insulin like growth factor-I (IGF-I) and insulin like growth factor bindingprotein-1 (IGFBP-1) from 101 women and 101 men randomly selected from the population registry. No gender differences in IGF-I levels were fmmd. IGF-1 decreases with advancing age in both sexes, whereas IGFBP-1 increases with age.Titrating the GH dose according to population based reference values of IGF-I might be a way to obtain a fairly physiological substitution dose of GH. We hypothesised that a safe and probably effective maintenance dose of GH should increase IGF-I to the mean or slightly below the mean according to age adjusted reference levels. Eighteen adult hypopituitary patients with severe GH deficiency were titrated in steps, according to age adjusted IGF-I levels, to an individual dose of recombinant GH. For comparison 17 untreated healthy control subjects were evaluated. Similar IGF-1 levels armmd the mean for corresponding age were obtained in both sexes, but the maintenance median GH dose was more than twice in the women compared to men. The :individual dose differed markedly and elderly patients needed lower GH doses due to unchanged GH-sensitivity. Six months on the maintenance GH dose induced changes in blood-glucose, lipids, and insulin sensitivity index, indicating increased insulin resistance, which compared with the controls, were a normalisation. No major changes were seen in the variables of the renin-angiotensin-system. A significant increase in atrial natriuretic peptide seems also to be a normalisation if compared with the controls. The patients had less muscle strength and endmance at baseline compared with the controls and increased the muscle strength and endmance about 10 % after GH-substitution, an effect associated with the increase in IGF-I.Paradoxically circulating IGF-I is decreased in type 1 diabetes despite increased GH levels. We studied 134 adult patients with type I diabetes (aged 20-60 years), without endogenous insulin secretion, and found that circulating IGF-I were decreased to about 70 % of the values in the reference population. No con·elation between glycaemic control and IGF-I levels was found.To conclude the GH dose obtained when normalising circulating IGF-I according to population-based IGF-I levels, depends on GH-sensitivity (gender) and the IGF-1 level aimed for (age). In comparison with matched controls several OR-dependent variables are improved. In type 1 diabetes, our results suggests that the low IGF-I levels are independent of glycaemic control, and can not be corrected with subcutaneous insulin substitution.
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5.
  • Gravholt, Claus Højbjerg, et al. (författare)
  • Clinical and epidemiological description of aortic dissection in Turner's syndrome.
  • 2006
  • Ingår i: Cardiology in the young. - 1047-9511. ; 16:5, s. 430-6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Women with Turner's syndrome have an increased risk of congenital cardiac malformations, ischaemic heart disease, hypertension and stroke. Aortic dissection seems to occur with increased frequency. AIM: To describe in more detail aortic dissection as encountered in Turner's syndrome, giving attention to clinical, histological and epidemiological aspects. MATERIALS AND METHODS: Based on a retrospective study, we describe the clinical, karyotypic, and epidemiological aspects of aortic dissection as encountered in cases of Turner's syndrome seen in Denmark and Sweden. RESULTS: The median age at onset of aortic dissection in 18 women was 35 years, ranging from 18 to 61 years. Fourteen of 18 women had a 45,X karyotype, while 2 patients had 45,X/45,XY, and 2 had the 45,X/46,X+r(X) complement, respectively. Echocardiography was performed in 10 of 18 patients before their acute illness, and showed signs of congenital cardiac disease, with either bifoliate aortic valves, dilation of the aortic root, or previous aortic coarctation evident in most patients. In 5 patients evidence of a bifoliate aortic valve was conclusive. Hypertension was present in 5 of 18 patients, while 10 of the patients died from aortic dissection, of so-called type A in 6, type B in 3, while in the final case the origin of dissection could not be determined. Biochemical analysis showed altered ratio between type I and type III collagen. Histology showed cystic medial necrosis in 3 of 7 cases. We estimated an incidence of dissection of 36 per 100,000 Turner's syndrome years, compared with an incidence of 6 per 100,000 in the general population, and a cumulated rate of incidence of 14, 73, 78, and 50 per 100,000 among 0-19, 20-29, 30-39, and 40+ year olds, respectively. CONCLUSION: Aortic dissection is extremely common in the setting of Turner's syndrome, and occurs early in life. Patients with Turner's syndrome should be offered a protocol for clinical follow-up similar to that provided for patients with Marfan syndrome, and each clinic should embrace a programme for follow-up.
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6.
  • Kołtowska-Häggström, Maria, 1957- (författare)
  • Quality of Life in Adult Patients with Growth Hormone Deficiency : Bridging the gap between clinical evaluation and health economic assessment
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The goals of this thesis are to evaluate quality of life (QoL) in adult patients with growth hormone deficiency (GHD) in relation to population normative data, to construct a preference-weighted index (utility) from a disease-specific QoL measure and to assess it in a clinical context.The study included samples from the general population and patients with GHD from four European populations: England & Wales, the Netherlands, Spain and Sweden. The country-specific patient cohorts were retrieved from KIMS (Pfizer International Metabolic Database). A questionnaire was developed that contained items from existing QoL questionnaires including, among others, Quality of Life Assessment in Growth Hormone Deficiency in Adults (QoL-AGHDA) and the EQ-5D. The QoL-AGHDA is a disease-specific measure for use in adults with GHD. The EQ-5D is a generic instrument which describes health states for which country-specific preference-based weights are available. Thus, it was possible to generate preference-weighted indices (utilities) based on data generated by both instruments. This thesis reports QoL-AGHDA normative values for the populations of England & Wales, the Netherlands, Spain and Sweden, and confirms the extent of QoL impairment in patients with GHD in comparison with the general population. Long-term GH replacement resulted in sustained improvements in overall QoL towards normative country-specific values, as well in most of the dimensions that were impaired before treatment. For use in health economic evaluations, models for generating utilities (QoL-AGHDAutility) from QoL-AGHDA were developed. It is believed that these models may facilitate medical decision making, given that they provide a tool for obtaining utilities in the absence of directly collected preference-weighted indices.QoL-AGHDAutility effectively monitored treatment effects in patients with GHD. Moreover, this study confirmed a QoL-AGHDAutility deficit before treatment and a gain after starting GH replacement. The novel aspect of the present approach was to apply preference-weighted indices derived from a disease-specific measure to assess QoL in the clinical context, together with patient demographic and clinical characteristics. The robustness of this analysis is reinforced by the fact that utilities in both general and patient populations were generated using the same methodology.
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