المؤلفون: Claire L Wood, Kieren G Hollingsworth, Edrina Bokaie, Eric Hughes, Robert Muni-Lofra, Anna Mayhew, Rod T Mitchell, Michela Guglieri, Joseph McElvaney, Timothy D Cheetham, Volker Straub

المصدر: Endocrine Connections, Vol 12, Iss 12, Pp 1-12 (2023)

مصطلحات موضوعية: puberty, duchenne muscular dystrophy, testosterone, muscle mri, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown. Objective: To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction. Methods: A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 y ears (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI. Results: Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol /L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL ( s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL ( s.d. 87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased. Interpretation: Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important.

وصف الملف: electronic resource

العلاقة: https://ec.bioscientifica.com/view/journals/ec/12/12/EC-23-0245.xmlTest; https://doaj.org/toc/2049-3614Test

الوصول الحر: https://doaj.org/article/db405beaad49493dbc40bf202b1d89dbTest

المؤلفون: Claire L Wood, Niamh Morrison, Michael Cole, Malcolm Donaldson, David B Dunger, Ruth Wood, Simon H S Pearce, Timothy D Cheetham

المصدر: European Thyroid Journal, Vol 11, Iss 1, Pp 1-8 (2023)

مصطلحات موضوعية: thyrotoxicosis, thionamide(s), anti-thyroid drugs, pediatric, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Objective: Patients with thyrotoxicosis are treated with anti-thyroid dru g (ATD) using block and replace (BR) or a smaller, titrated dose of ATD (dose titration, DT). Design: A multi-centre, phase III, open-label trial of newly diagnosed paediatric thyrotoxicosis patients randomised to BR/DT. We compared the bi ochemical response to BR/DT in the first 6 months of therapy. Methods: Patients commenced 0.75 mg/kg carbimazole (CBZ) daily with rand omisation to BR/DT. We examined baseline patient characteristics, CBZ dose, time to serum thyroid-stimulating hormone (TSH)/free thyroxine (FT4) normalisation and BMI Z-score change. Results: There were 80 patients (baseline) and 78 patients (61 female) at 6 months. Mean CBZ dose was 0.9 mg/kg/day (BR) and 0.5 mg/kg/day (DT). There w as no difference in time to non-suppressed TSH concentration; 16 of 39 patients (BR ) and 11 of 39 (DT) had suppressed TSH at 6 months. Patients with suppressed TSH had hi gher mean baseline FT4 levels (72.7 vs 51.7 pmol/L; 95% CI for difference 1.73, 31. 7; P = 0.029). Time to normalise FT4 levels was reduced in DT (log-rank test, P = 0.049) with 50% attaining normal FT4 at 28 days (95% CI 25, 32) vs 35 days in BR (95% CI 28, 58). Mean BMI Z-score increased from 0.10 to 0.81 at 6 months (95% CI for difference 0 .57, 0.86; P < 0.001) and was greatest in patients with higher baseline FT4 concentration s. Conclusions: DT-treated patients normalised FT4 concentrations more quickly than BR. Overall, 94% of patients have normal FT4 levels after 6 months, but 33% still have TSH suppression. Excessive weight gain occurs with both BR and DT t herapy.

وصف الملف: electronic resource

العلاقة: https://etj.bioscientifica.com/view/journals/etj/11/1/ETJ-21-0043.xmlTest; https://doaj.org/toc/2235-0802Test

الوصول الحر: https://doaj.org/article/88164a4fad95423e8438fca1d143efa1Test

المؤلفون: Yolanda Alins Sahun, Tim Cheetham, Christopher Boot, Volker Straub, Claire L. Wood

المصدر: BMC Endocrine Disorders, Vol 21, Iss 1, Pp 1-5 (2021)

مصطلحات موضوعية: Salivary testosterone, Duchenne muscular dystrophy, Androgen deficiency, Long-term glucocorticoid therapy, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Abstract Background Many young adults with Duchenne Muscular Dystrophy (DMD) receive long-term glucocorticoids (GC). GC can cause hypogonadotrophic hypogonadism and adolescents may therefore be candidates for pubertal induction. It is unclear whether men with DMD on or off GC have age-appropriate endogenous testosterone production. Methods We undertook a quality improvement project to assess the feasibility of measuring salivary testosterone (SalT) levels in men with DMD at home. A Sal-T sampling kit was sent by post to all patients with DMD, aged 17 and older, registered at the John Walton Muscular Centre in Newcastle (n = 75). Submitted Sal-T samples were collected and submitted for analysis. Results Twenty-eight out of seventy-five patients returned samples (age range: 17–34 years). 6/28 samples were unsuitable for analysis. Overall Sal-T levels (n = 22) were significantly lower than in the healthy population (178 ± 107 v 287 ± 109 pmol/l, p = 0.0001). Sal-T was lower in those on GC compared to those off GC (144 ± 81 versus 218 ± 125 pmol/l, p = 0.05). Three patients were unable to collect a sample due to ventilator dependence. Conclusion Sal T can provide information about androgen status in DMD patients at home, overcoming barriers such as mobility difficulties and challenging venepuncture. However we only obtained samples in a minority of patients suggesting that Sal-T measurement may not be appropriate or acceptable to everyone. There needs to be a more detailed exploration of the barriers to sample submission.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1472-6823Test

الوصول الحر: https://doaj.org/article/b17c93a4ab3543b6a80e53102ae774fbTest

المؤلفون: Luling Lin, Greg Gamble, Caroline Crowther, Frank Bloomfield, Massimo Agosti, Stephanie A. Atkinson, Augusto Biasini, Nicholas D. Embleton, Fernando Lamy-Filho, Christoph Fusch, Maria L. Giannì, H. Gozde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Kenneth Stroemmen, Maw Tan, Francesco Tandoi, Claire L. Wood, Gitte Zachariassen, Jane E. Harding

مصطلحات موضوعية: Paediatrics, macronutrient supplements, preterm infants, small-for-gestational-age infants, growth, cognitive function, metabolic risk, individual participants data meta-analysis, systematic review

الوصف: We undertook an individual participant data meta-analysis to explore the effect of macronutrient supplements given to preterm and small-for-gestational-age infants on their developmental, metabolic and growth outcomes. In this project, we found supplementation slightly increases early growth but did not improve later cognitive function or increase risks of diabetes and heart disease. Supplementation also improves motor function in toddlers, particularly for girls, although the long-term effects are unclear. The protocol of ESSENCE IPD-MA project was published at BMJ Open available at doi:10.1136/bmjopen-2019-033438 The findings are published at Nutrients available at doi:10.3390/nu14030418 and doi:10.3390/nu14020392 The deidentified participant data analysed for the ESSENCE IPD-MA project remain the property of the ESSENCE-IPD Trialist Group. Researchers should contact the original trial investigator directly for access to these data. Attached are the statistical analysis plan and data dictionary. Researchers are able to use this information and the provided contact address (researchhub@auckland.ac.nz) to request further information through the Data Access Committee of the Liggins Institute. The Liggins Institute reserves the right to charge a fee to cover the costs of making data available, if needed, for data requests that require additional work to prepare.

العلاقة: https://figshare.com/articles/online_resource/Sex-Specific_Effects_of_Nutritional_Supplements_for_Infants_Born_Early_or_Small_An_Individual_Participant_Data_Meta-Analysis_ESSENCE_IPD-MA_/18729068Test

الإتاحة: https://doi.org/10.17608/k6.auckland.18729068.v1Test
https://figshare.com/articles/online_resource/Sex-Specific_Effects_of_Nutritional_Supplements_for_Infants_Born_Early_or_Small_An_Individual_Participant_Data_Meta-Analysis_ESSENCE_IPD-MA_/18729068Test

المؤلفون: Claire L. Wood, Robert Tinnion, Kieren G. Hollingsworth, Michael I. Trenell, Mark S. Pearce, Tim D. Cheetham, Nicholas D. Embleton

المصدر: Nutrients; Volume 14; Issue 23; Pages: 5045

مصطلحات موضوعية: preterm, muscle, vitamin D

جغرافية الموضوع: agris

الوصف: Whilst several studies have explored adolescent metabolic and cognitive function after preterm birth, few have explored muscle function and physical activity. We set out to examine the relationship between gestational age and muscle metabolism in a cohort of adolescents who were born preterm. Participants were recruited from the Newcastle preterm birth growth study cohort. They did not have severe neurological disease and were not on daily medication. Participants underwent an assessment of oxidative muscle function using phosphorus magnetic resonance spectroscopy that included the half-time for recovery of equilibrium of phosphocreatine, τ½PCr. In addition, we measured key variables that might affect muscle function including physical activity levels determined by 3-day accelerometry, body composition using air displacement plethysmography, insulin sensitivity using the homeostatic model assessment/Matsuda index and serum vitamin D concentrations. 60 adolescents (35F) median age 15.6 years (range 12.1–18.8) with a median gestation of 31 weeks (range 24 to 34 weeks) underwent a single assessment. Males were more active and spent less time in sedentary mode. Time spent in light activity was associated with insulin sensitivity (IS) (Matsuda Index; p < 0.05) but there were no strong correlations between activity levels and gestational age. Greater fat mass, waist circumference and body mass index were all associated with lower IS. Gestational age was negatively associated with adjusted measures of oxidative muscle function (τ½PCr). In a stepwise multivariate linear regression model, gestational age at birth was the most significant predictor of oxidative muscle function (p = 0.005). Higher serum vitamin D levels were also associated with faster phosphocreatine recovery time (p = 0.045). Oxidative function in the skeletal muscle of adolescents born preterm is associated with gestational age and vitamin D concentrations. Our study suggests that being born preterm may have a long-term impact ...

وصف الملف: application/pdf

العلاقة: Pediatric Nutrition; https://dx.doi.org/10.3390/nu14235045Test

الإتاحة: https://doi.org/10.3390/nu14235045Test

المؤلفون: Luling Lin, Greg D. Gamble, Caroline A. Crowther, Frank H. Bloomfield, Massimo Agosti, Stephanie A. Atkinson, Augusto Biasini, Nicholas D. Embleton, Mary S. Fewtrell, Fernando Lamy-Filho, Christoph Fusch, Maria L. Gianni, H. Gozde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Atul Singhal, Kenneth Stroemmen, Maw J. Tan, Francesco M. Tandoi, Claire L. Wood, Gitte Zachariassen, Jane E. Harding

المصدر: Nutrients; Volume 14; Issue 3; Pages: 418

مصطلحات موضوعية: macronutrient supplementation, preterm infants, small-for gestational-age infants, cognitive function, metabolic risk, individual participants data meta-analysis, systematic review

جغرافية الموضوع: agris

الوصف: Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

وصف الملف: application/pdf

العلاقة: Pediatric Nutrition; https://dx.doi.org/10.3390/nu14030418Test

الإتاحة: https://doi.org/10.3390/nu14030418Test

المؤلفون: Luling Lin, Greg D. Gamble, Caroline A. Crowther, Frank H. Bloomfield, Massimo Agosti, Stephanie A. Atkinson, Augusto Biasini, Nicholas D. Embleton, Fernando Lamy Filho, Christoph Fusch, Maria L. Gianni, Hayriye Gözde Kanmaz Kutman, Winston Koo, Ita Litmanovitz, Colin Morgan, Kanya Mukhopadhyay, Erica Neri, Jean-Charles Picaud, Niels Rochow, Paola Roggero, Kenneth Stroemmen, Maw J. Tan, Francesco M. Tandoi, Claire L. Wood, Gitte Zachariassen, Jane E. Harding

المصدر: Nutrients; Volume 14; Issue 2; Pages: 392

مصطلحات موضوعية: macronutrient supplementation, preterm infants, small-for-gestational-age infants, growth, individual participants data meta-analysis, systematic review

جغرافية الموضوع: agris

الوصف: Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) −0.11[95% CI −0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

وصف الملف: application/pdf

العلاقة: Pediatric Nutrition; https://dx.doi.org/10.3390/nu14020392Test

الإتاحة: https://doi.org/10.3390/nu14020392Test

المؤلفون: Yolanda Alins Sahun (10581762), Tim Cheetham (8415396), Christopher Boot (10581765), Volker Straub (251869), Claire L. Wood (10581768)

مصطلحات موضوعية: Biochemistry, Genetics, Science Policy, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Salivary testosterone, Duchenne muscular dystrophy, Androgen deficiency, Long-term glucocorticoid therapy

الوصف: Additional file 1. Self-assessment questionnaire.

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_1_of_Measurement_of_salivary_testosterone_in_adolescents_and_young_men_with_Duchenne_muscular_dystrophy/14398554Test

الإتاحة: https://doi.org/10.6084/m9.figshare.14398554.v1Test

المؤلفون: Claire L. Wood, Karla J. Suchacki, Rob van ’t Hof, Will P. Cawthorn, Scott Dillon, Volker Straub, Sze Choong Wong, Syed F. Ahmed, Colin Farquharson, Annemieke Aartsma-Rus, James Dowling, Maaike van Putten

المصدر: Disease Models & Mechanisms, Vol 13, Iss 2 (2020)

مصطلحات موضوعية: duchenne muscular dystrophy, growth, skeletal development, marrow adiposity, micro-ct, growth plate, Medicine, Pathology, RB1-214

الوصف: The muscular dystrophy X-linked (mdx) mouse is commonly used as a mouse model of Duchenne muscular dystrophy (DMD). Its phenotype is, however, mild, and other mouse models have been explored. The mdx:Cmah−/− mouse carries a human-like mutation in the Cmah gene and has a severe muscle phenotype, but its growth and bone development are unknown. In this study, we compared male mdx, mdx:Utrn+/−, mdx:Cmah−/− and wild-type (WT) mice at 3, 5 and 7 weeks of age to determine the suitability of the mdx:Cmah−/− mouse as a model for assessing growth and skeletal development in DMD. The mdx:Cmah−/− mice were lighter than WT mice at 3 weeks, but heavier at 7 weeks, and showed an increased growth rate at 5 weeks. Cortical bone fraction as assessed by micro-computed tomography was greater in both mdx and mdx:Cmah−/− mice versus WT mice at 7 weeks. Tissue mineral density was also higher in mdx:Cmah−/− mice at 3 and 7 weeks. Gene profiling of mdx:Cmah−/− bone identified increased expression of Igf1, Igf1r and Vegfa. Both the mdx and mdx:Cmah−/− mice showed an increased proportion of regulated bone marrow adipose tissue (BMAT) but a reduction in constitutive BMAT. The mdx:Cmah−/− mice show evidence of catch-up growth and more rapid bone development. This pattern does not mimic the typical DMD growth trajectory and therefore the utility of the mdx:Cmah−/− mouse for studying growth and skeletal development in DMD is limited. Further studies of this model may, however, shed light on the phenomenon of catch-up growth. This article has an associated First Person interview with the first author of the paper.

وصف الملف: electronic resource

العلاقة: http://dmm.biologists.org/content/13/2/dmm040659Test; https://doaj.org/toc/1754-8403Test; https://doaj.org/toc/1754-8411Test

الوصول الحر: https://doaj.org/article/115a85de5287469e82f3c757ce592bafTest

المؤلفون: Evlyn James, Claire L. Wood, Harish Nair, Thomas C. Williams

المصدر: BMC Pediatrics, Vol 18, Iss 1, Pp 1-12 (2018)

مصطلحات موضوعية: Menarche, Follow up studies, Pediatrics, RJ1-570

الوصف: Abstract Background An estimated 11% of births occur preterm, and survival is improving. Early studies suggested an association between preterm birth and earlier puberty. Given the adverse outcomes associated with early puberty this could have significant public health implications. The objective of this review was to assess the timing of puberty after preterm birth. Methods Pubmed, Embase, Popline, Global Health and Global Health Library were searched using terms relating to “premature birth”, “menarche”, “puberty” and “follow up studies”. Inclusion criteria were a population consisting of pubertal or post-pubertal adolescents and adults; studies which defined preterm delivery in participants and compared outcomes to those after term delivery; and a quantitative assessment of pubertal onset. Assessment of risk of bias was conducted using principles from the Critical Appraisal Study Process. Results Our search identified 1051 studies, of which 16 met the inclusion criteria. In females, 8 studies found no association between preterm birth and the timing of menarche. Five studies found earlier onset in preterm infants, 1 found later onset, and 1 showed both earlier and later menarche, depending on birth weight. The range of effect of studies showing earlier menarche was - 0.94 to −0.07 years in the preterm group, with a median of - 0.3 years. In males, 2 studies showed earlier onset of puberty in the preterm group, 5 showed no difference, and 1 showed later onset. Most studies did not present outcomes in the form of a mean with standard deviation, precluding a meta-analysis. There was insufficient data to address potential confounding factors. Conclusions The published evidence does not suggest that being born preterm leads to a significant acceleration in the onset of puberty. This should prove reassuring for public health purposes, and for clinicians counseling parents of infants born preterm.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12887-017-0976-8Test; https://doaj.org/toc/1471-2431Test

الوصول الحر: https://doaj.org/article/c07edd24ef084c2b857c1f6c8d1e74ffTest