| 1. |
- Allen, David B, et al.
(författare)
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GH Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
- 2016
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 174:2, s. 1-9
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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. |
- Nicholson, George, et al.
(författare)
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A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection
- 2011
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:9, s. e1002270-
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Tidskriftsartikel (refereegranskat)abstract
- We have performed a metabolite quantitative trait locus (mQTL) study of the 1H nuclear magnetic resonance spectroscopy (1H NMR) metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by 1H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs). Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10−11<p<2.8×10−23). Three of these—trimethylamine, 3-amino-isobutyrate, and an N-acetylated compound—were measured in urine. The other—dimethylamine—was measured in plasma. Trimethylamine and dimethylamine mapped to a single genetic region (hence we report a total of three implicated genomic regions). Two of the three hit regions lie within haplotype blocks (at 2p13.1 and 10q24.2) that carry the genetic signature of strong, recent, positive selection in European populations. Genes NAT8 and PYROXD2, both with relatively uncharacterized functional roles, are good candidates for mediating the corresponding mQTL associations. The study's longitudinal twin design allowed detailed variance-components analysis of the sources of population variation in metabolite levels. The mQTLs explained 40%–64% of biological population variation in the corresponding metabolites' concentrations. These effect sizes are stronger than those reported in a recent, targeted mQTL study of metabolites in serum using the targeted-metabolomics Biocrates platform. By re-analysing our plasma samples using the Biocrates platform, we replicated the mQTL findings of the previous study and discovered a previously uncharacterized yet substantial familial component of variation in metabolite levels in addition to the heritability contribution from the corresponding mQTL effects.
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| 3. |
- Schlumberger, Martin, et al.
(författare)
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Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective.
- 2004
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 150:2, s. 105-12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Because differentiated (follicular and papillary) thyroid cancer (DTC) may recur years after initial treatment, the follow-up of patients with DTC is long term. However, this population has changed, with more individuals being discovered at an earlier stage of the disease, so that previous follow-up protocols based mostly on data from high-risk patients no longer apply. We sought to develop an improved protocol for the follow-up of low-risk patients with DTC based on the findings of recent studies. METHODS: We analysed recent literature on the follow-up of DTC. RESULTS: Recent large studies have produced three important findings: (i) in patients with low-risk DTC with no evidence of disease up to the 6- to 12-month follow-up, diagnostic whole-body scan adds no information when serum thyroglobulin (Tg) is undetectable and interference from anti-Tg antibodies is absent; (ii) use of recombinant human thyroid-stimulating hormone to aid Tg measurement is effective and provides greater safety, quality-of-life and work productivity than does levothyroxine withdrawal with its attendant hypothyroidism; and (iii) ultrasonography performed by an experienced operator is the most sensitive means of detecting neck recurrences of DTC. CONCLUSIONS: We present a revised follow-up protocol for low-risk patients taking into account the above findings. This protocol should help clinicians enter a new era of monitoring characterized by greater safety, simplicity, convenience and cost savings.
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