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      Short-Term Growth after Withdrawal of Exogenous Glucocorticoids

      ,

      Hormone Research in Paediatrics

      S. Karger AG

      Knemometry, Growth, Prednisolone, Glucocorticoids, Steroids

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          Abstract

          Background: The growth-suppressive effect of systemic glucocorticoids in children is well established, however, recovery of growth after withdrawal of short-term treatment in school-age children has not been evaluated. Objective: To assess short-term growth after withdrawal of systemic glucocorticoids. Methods: A post-hoc analysis of data from a double-blind lower leg growth trial which compared 5 mg prednisolone once daily in the evening with placebo was performed. The study consisted of run-in, treatment, wash-out and run-out periods of 1 week duration. In 10 children with asthma (mean age 11 years) lower leg growth measured with the knemometer could be studied up to 3 weeks after withdrawal of prednisolone. Results: Mean (SEM) lower leg growth rates during run-in, prednisolone treatment and the first, second and third weeks after withdrawal of prednisolone were 0.48 (0.15), –0.27 (0.20), 0.53 (0.19), 0.72 (0.16) and 0.66 (0.14) mm/week, p < 0.001. Mean growth rates during run-in and the first, second and third weeks after withdrawal of prednisolone did not vary, p = 0.68. Conclusion: Recovery of suppressed lower leg growth rates occurs within a week after withdrawal of exogenous glucocorticoids.

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          Most cited references 9

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          Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells.

          The inhibitor of apoptosis (IAP) protein Survivin is expressed in most cancers and is a key factor in maintaining apoptosis resistance. Although several IAPs have been shown to act as direct inhibitors of caspases, the precise antiapoptotic function of Survivin remains controversial. To clarify the mechanism by which Survivin protects cells, we investigated the kinetics of apoptosis and apoptotic events following Survivin inhibition utilizing a melanoma cell line harboring a tetracycline-regulated Survivin dominant-negative mutant (Survivin-T34A). Blocking Survivin resulted in both caspase activation and apoptosis; however, the level of apoptosis was only partially reduced by caspase inhibition. Survivin blockade also resulted in mitochondrial events that preceded caspase activation, including depolarization and release of cytochrome c and Smac/DIABLO. Levels of other IAPs were not altered in Survivin-targeted cells, although modest cleavage of XIAP and Livin was observed. The earliest proapoptotic event observed in Survivin-targeted cells was nuclear translocation of mitochondrial apoptosis-inducing factor (AIF), known to trigger both apoptotic mitochondrial events and caspase-independent DNA fragmentation. These findings suggest that a key antiapoptotic function of Survivin relates to inhibition of mitochondrial and AIF-dependent apoptotic pathways, and its expression in melanoma and other cancers likely protects against both caspase-independent and -dependent apoptosis.
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            The Analysis of Short-Term Growth

            The analysis of short-term growth needs repetitive measurements of body stature or of segments of the body. When body stature is measured at monthly intervals, an irregular incremental pattern becomes obvious with a number of large-scale components such as series of prepubertal and pubertal growth spurts, seasonal influences on height gain, and influences of the psychosocial and economic background. When measurement intervals decrease, incremental patterns appear even more irregular, and a number of short-scale components become apparent that are distinct from measurement error. The review summarizes the analysis of short-term growth, and presents the current findings supporting different views on how growth progresses at short term. In particular, observations are presented that suggest growth being a pulsatile, a periodic, a saltatory, and a chaotic event. Some recent animal studies and studies in human newborns are added in detail as they illustrate short-term growth on the basis of accurate 24-hour measurements of the lower leg. The latter investigations support the idea of short-term growth being characterized by chaotic series of ‘mini growth spurts’ that occur at intervals of approximately 4–5 days, not only in human neonates, but also in rats. The amplitude of mini growth spurts ranges between 2 and some 10 mm, and growth velocity of each spurt also varies considerably so that one spurt needs between less than 1 and up to several days for completion.
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              Short term linear growth in asthmatic children during treatment with prednisolone.

              To see whether small daily doses of prednisolone have any adverse effect on short term linear growth in children with mild asthma. Double blind, random order crossover trial of two dosages of prednisolone. During run in and washout periods patients were given placebo. All treatment periods were of two weeks' duration. Outpatient clinic referrals in a secondary referral centre. 14 Children (10 boys) aged 7-11 years with normal growth velocity during the previous year, no signs of puberty, and no history of receiving systemic or topical steroids during the two months before the study. One child was excluded because his pulmonary function deteriorated and another was withdrawn because of varicella. 2.5 and 5.0 mg prednisolone daily given in divided dosage in the morning and evening. Growth of the lower leg as measured twice a week by knemometry. A significant reduction in mean growth velocity of the lower leg occurred in both prednisolone treatment periods. The mean difference between the run in period and the treatment period with 2.5 mg prednisolone daily was 0.63 mm/week (95% confidence interval 0.47 to 0.80 mm/week) and between the run in period and the treatment period with 5.0 mg prednisolone daily 0.57 mm/week (0.38 to 0.77 mm/week). Small daily doses of prednisolone suppress short term linear growth in children with mild asthma. The clinical relevance of this finding needs further study.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2005
                October 2005
                26 October 2005
                : 64
                : 3
                : 116-118
                Affiliations
                Children’s Clinic Randers, Randers, Denmark
                Article
                88348 Horm Res 2005;64:116–118
                10.1159/000088348
                16166782
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, References: 11, Pages: 3
                Categories
                Original Paper

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