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Anton Geerinck Olivier Bruyère Médéa Locquet Jean-Yves Reginster Charlotte Beaudart 《Advances in therapy》2018,35(11):1842-1858
Introduction
The Sarcopenia Quality of Life (SarQoL®) questionnaire was developed to provide a patient-reported outcome measure specific to sarcopenia. Its psychometric properties indicate that it is a valid and reliable instrument. However, until now, its ability to detect change over time has not been examined. Therefore, the objective of this study is to evaluate the responsiveness (also known as sensitivity to change) of the SarQoL® questionnaire in a prospective, longitudinal cohort of community-dwelling, older, sarcopenic subjects.Methods
Sarcopenic subjects from the SarcoPhAge (Sarcopenia and Physical impairment with advancing Age) study were included. Responsiveness was evaluated with nine pre-specified hypotheses on the correlation between the evolution of the SarQoL® scores after a 2-year interval and the evolution of the scores on the Short Form-36 (SF-36) and the Euroqol 5-dimension (EQ-5D) questionnaires. This technique considers responsiveness to be a form of longitudinal validity. Additionally, standardized response means were also calculated to compare the quantity of change measured by the different questionnaires.Results
A total of 42 sarcopenic subjects were included. The median age of the sample was 72.9 (68.9–78.8) years, 59.5% were female, and the mean body mass index was 23.3 (20.4–25.7) kg/m2. A good responsiveness was observed, as evidenced by the confirmation of eight out of nine hypotheses, well above the 75% confirmation threshold. The standardized response mean of the Overall SarQoL® score was significantly higher than those of the SF-36 Physical Component Summary (p?=?0.005), the EQ-5D Utility Index (p?<?0.001) and the Euroqol visual analogue scale (p?=?0.003).Conclusion
The first data available on the ability of the SarQoL® questionnaire to detect change over time indicates that the questionnaire has good responsiveness. This, together with the previously established psychometric properties, confirms that the SarQoL® questionnaire is a relevant instrument for the assessment of quality of life in sarcopenic populations.103.
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Surface‐expressed insulin receptors as well as IGF‐I receptors both contribute to the mitogenic effects of human insulin and its analogues 下载免费PDF全文
Anders Lundby Pernille Bolvig Anne Charlotte Hegelund Bo F. Hansen Jesper Worm Anne Lützen Nils Billestrup Christine Bonnesen Martin B. Oleksiewicz 《Journal of applied toxicology : JAT》2015,35(7):842-850
There is a medical need for new insulin analogues. Yet, molecular alterations to the insulin molecule can theoretically result in analogues with carcinogenic effects. Preclinical carcinogenicity risk assessment for insulin analogues rests to a large extent on mitogenicity assays in cell lines. We therefore optimized mitogenicity assay conditions for a panel of five cell lines. All cell lines expressed insulin receptors (IR), IGF‐I receptors (IGF‐IR) and hybrid receptors, and in all cell lines, insulin as well as the comparator compounds X10 and IGF‐I caused phosphorylation of the IR as well as IGF‐IR. Insulin exhibited mitogenicity EC50 values in the single‐digit nanomolar to picomolar range. We observed correlations across cell types between (i) mitogenic potency of insulin and IGF‐IR/IR ratio, (ii) Akt phosphorylation and mitogenic potency and (iii) Akt phosphorylation and IR phosphorylation. Using siRNA‐mediated knockdown of IR and IGF‐IR, we observed that in HCT 116 cells the IR appeared dominant in driving the mitogenic response to insulin, whereas in MCF7 cells the IGF‐IR appeared dominant in driving the mitogenic response to insulin. Together, our results show that the IR as well as IGF‐IR may contribute to the mitogenic potency of insulin. While insulin was a more potent mitogen than IGF‐I in cells expressing more IR than IGF‐IR, the hyper‐mitogenic insulin analogue X10 was a more potent mitogen than insulin across all cell types, supporting that the hyper‐mitogenic effect of X10 involves the IR as well as the IGF‐IR. These results are relevant for preclinical safety assessment of developmental insulin analogues. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Ola Brodin Staffan Eksborg Marita Wallenberg Charlotte Asker-Hagelberg Erik H. Larsen Dag Mohlkert Clara Lenneby-Helleday Hans Jacobsson Stig Linder Sougat Misra Mikael Bj?rnstedt 《Nutrients》2015,7(6):4978-4994
Background: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients’ refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. Materials and Methods: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. Results and Conclusion: MTD was defined as 10.2 mg/m2, with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m2 under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy. 相似文献
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Lidove O Piette JC Charlotte F Cassoux N Correas JM Papo T 《European Journal of Internal Medicine》2004,15(2):121-124
We report on hypophysitis associated with a prominent lymphoid infiltration of salivary and lachrymal glands in a 35-year-old woman with a dramatic response to steroids. Four years later, overt Graves' disease developed. To our knowledge, pseudotumoral lymphocytic infiltration of both lachrymal and salivary glands has never been described in association with hypophysitis. Benign lymphocytic hypophysitis may belong to a spectrum that extends from low-grade lymphoid proliferation to autoimmune disease. Such a process may follow a regional tissue distribution including pituitary, thyroid, lachrymal and salivary glands. 相似文献