14 results on '"Ahmed, S. F."'
Search Results
2. The relationship between adiposity, bone density and microarchitecture is maintained in young women irrespective of diabetes status.
- Author
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Abdalrahaman N, McComb C, Foster JE, Lindsay RS, Drummond R, McKay GA, Perry CG, and Ahmed SF
- Subjects
- Adiposity genetics, Adolescent, Adult, Bone Density genetics, Diabetes Mellitus, Type 1 pathology, Female, Humans, Magnetic Resonance Imaging, Mass Spectrometry, Young Adult, Adiposity physiology, Bone Density physiology, Diabetes Mellitus, Type 1 metabolism, Femur Neck metabolism, Lumbar Vertebrae metabolism
- Abstract
Background: The relationship between bone health and adiposity and how it may be affected in people with chronic metabolic conditions is complex., Methods: Seventeen women with type 1 diabetes mellitus (T1DM) and nine age-matched healthy women with a median age of 22.6 years (range, 17.4, 23.8) were studied by 3T MRI and MR spectroscopy to assess abdominal adiposity, tibial bone microarchitecture and vertebral bone marrow adiposity (BMA). Additional measures included DXA-based assessments of total body (TB), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and fat mass (FM)., Results: Although women with T1DM had similar BMI and BMA to the controls, they had higher visceral and subcutaneous adiposity on MRI (P<.05) and total body FM by DXA (P=.03). Overall, in the whole cohort, a clear inverse association was evident between BMA and BMD at all sites (P<.05). These associations remained significant after adjusting for age, BMI, FM and abdominal adiposity. In addition, visceral adiposity, but not subcutaneous adiposity, showed a positive association with BMA (r, .4, P=.03), and a negative association with total body BMD (r, .5, P=.02). Apparent trabecular separation as assessed by MRI showed an inverse association to total body BMD by DXA (r, -.4, P=.04)., Conclusion: Irrespective of the presence of an underlying metabolic condition, young women display a negative relationship between MRI-measured BMA and DXA-based assessment of BMD. Furthermore, an association between BMA and visceral adiposity supports the notion of a common origin of these two fat depots., (© 2017 John Wiley & Sons Ltd.)
- Published
- 2017
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3. MRI-based abnormalities in young adults at risk of adverse bone health due to childhood-onset metabolic & endocrine conditions.
- Author
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McComb C, Harpur A, Yacoubian C, Leddy C, Anderson G, Shepherd S, Perry C, Shaikh MG, Foster J, and Ahmed SF
- Subjects
- Adiposity, Adolescent, Adult, Bone Density, Case-Control Studies, Female, Growth Hormone metabolism, Humans, Lumbar Vertebrae pathology, Magnetic Resonance Spectroscopy, Male, Middle Aged, Phantoms, Imaging, Reproducibility of Results, Risk, Young Adult, Bone Marrow pathology, Magnetic Resonance Imaging methods, Osteogenesis Imperfecta physiopathology
- Abstract
Objective: Traditional methods of bone densitometry may not provide a comprehensive assessment of bone health. We aimed to assess bone micro-architecture and bone marrow adiposity (BMA) by MRI in adults with osteogenesis imperfecta (OI) and endocrinopathy including GH deficiency and/or hypogonadism., Measurements: High-resolution micro-MRI images were acquired at the tibia using 3T MRI to calculate parameters of bone micro-architecture in seven adults with OI and 10 adults with endocrinopathies. MR Spectroscopy was performed in participants to calculate vertebral BMA, which was expressed as percentage fat fraction (%FF). Lumbar spine DXA was performed to assess bone mineral density. The MRI data were compared with a group of 22 healthy adults who were divided into two age-matched control groups., Results: Intra-operator repeatability was high, with an average CoV of 1% for micro-MRI and 2·5% for MRS. The ratio of apparent bone volume to total volume (appBV/TV) in the endocrinopathy and OI groups was lower than in age-matched control groups (P = 0·003 and P = 0·008 respectively). A weak association between DXA BMD and appBV/TV was also observed (r = 0·5, P = 0·045). %FF was higher in the endocrinopathy group than in the age-matched control group (P = 0·005), but no difference in %FF was observed between the OI group and their age-matched control group (P = 0·26)., Conclusions: MRI provides valuable detailed information on the micro-architecture and adiposity of bones and is capable of showing clear differences in bone parameters in a range of clinical conditions associated with abnormal bone health., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2014
- Full Text
- View/download PDF
4. The growth hormone insulin-like growth factor 1 axis in children and adolescents with inflammatory bowel disease and growth retardation.
- Author
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Wong SC, Smyth A, McNeill E, Galloway PJ, Hassan K, McGrogan P, and Ahmed SF
- Subjects
- Adolescent, Age Determination by Skeleton, Body Height physiology, Child, Drug Resistance physiology, Female, Growth Disorders blood, Growth Disorders complications, Human Growth Hormone blood, Human Growth Hormone deficiency, Humans, Inflammatory Bowel Diseases blood, Inflammatory Bowel Diseases complications, Insulin Resistance physiology, Insulin-Like Growth Factor I analysis, Male, Puberty metabolism, Puberty physiology, Retrospective Studies, Signal Transduction physiology, Growth Disorders metabolism, Human Growth Hormone metabolism, Inflammatory Bowel Diseases metabolism, Insulin-Like Growth Factor I metabolism
- Abstract
Context: There is scarce knowledge about the growth hormone (GH) insulin-like growth factor-1 (IGF1) axis in children & adolescents with inflammatory bowel disease (IBD) and growth retardation., Objective: To describe the pattern of GH and IGF1 secretion in children & adolescents with IBD., Design: A retrospective review of 28 patients (23 M) of IBD (25 Crohn's Disease and three Ulcerative Colitis) and growth retardation who had investigation of the GH/IGF-1 axis. Height velocity (HV) and serum IGF1 were converted to standard deviation score (SDS); to account for delayed puberty in girls over 11 years and boys over 12 years, HV and serum IGF1 SDS were adjusted for bone age., Results: Median (range) age and Ht SDS at the time of endocrine evaluation was 14.3 years (7.7,17.0) and -2.0(-3.6,-0.9), respectively. Median HVSDS over the prior 12 months was -2.2(-7.7,2.8). Median peak serum GH on insulin tolerance test (ITT) was 5.8 mcg/l (1.3, 24.0), and median serum IGF1 SDS was -0.9(-3.1, 0.1). Five of 28 (18%) had a peak serum GH of >12 mcg/l. Overall, four had biochemical evidence of functional GH deficiency (peak GH < 3 mcg/l and IGF1 SDS < 0) and 11 children had biochemical evidence suggesting GH resistance (peak GH > 6 mcg/l and IGF1 SDS < 0). However, only one child had a peak serum GH > 6 mcg/l and a very low IGF1 SDS of <-2.0. There was a negative association between peak serum GH and Ht SDS (r = -0.49, P = 0.008), but there was no association with HV and there was no association between IGF1 SDS and Ht or HV SDS. IGF1 SDS showed a negative association with erythrocyte sedimentation rate (r = -0.41, P = 0.04)., Conclusion: Growth retardation in children and adolescents with IBD is commonly associated with a range of biochemical abnormalities ranging from functional GH deficiency to GH resistance. In these children, poor relationship between systemic markers of growth and height velocity point to an important role of growth factors at the target organ level in modulating growth in children with IBD. The value of assessing the GH/IGF-1 axis and whether it predicts subsequent response to growth-promoting therapy requires further exploration.
- Published
- 2010
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5. The concordance between serum anti-Mullerian hormone and testosterone concentrations depends on duration of hCG stimulation in boys undergoing investigation of gonadal function.
- Author
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Ahmed SF, Keir L, McNeilly J, Galloway P, O'Toole S, and Wallace AM
- Subjects
- Anti-Mullerian Hormone standards, Child, Diagnostic Techniques, Endocrine standards, Disorders of Sex Development blood, Disorders of Sex Development physiopathology, Drug Administration Schedule, Female, Humans, Male, Osmolar Concentration, Reference Values, Retrospective Studies, Statistics as Topic, Stimulation, Chemical, Testosterone standards, Time Factors, Anti-Mullerian Hormone blood, Chorionic Gonadotropin administration & dosage, Disorders of Sex Development diagnosis, Gonads physiology, Testosterone blood
- Abstract
Background: In boys undergoing investigation of gonadal function, the relationship between a single measurement of serum anti-Mullerian hormone (AMH) and hCG stimulated serum testosterone is unclear., Aim: The aim of the study was to assess concordance between serum AMH and testosterone concentrations following hCG stimulation of two different durations., Methods: Samples from 284 children (M : F, 154 : 130) with a median age of 8 years (10th, 90th centiles, 0.25, 14) were used to establish an AMH reference range. Clinical data were reviewed in boys undergoing investigation of gonadal function and who had an AMH measurement and a hCG stimulated (3-day or 3-week) (n = 26) testosterone. Of these 26 boys, 11 had combined genital anomalies, whereas the rest had conditions such as isolated hypospadias, undescended testes or microphallus. Normal testosterone response to hCG stimulation was defined as a level greater than 3.5 nmol at day 4 and 9.5 nmol/l at day 22., Results: In the reference group, the 5th centile AMH for boys below 1 year was 215 pmol/l and between 1 and 8 years 180 pmol/l. The 95th centile for girls for these respective age groups was 30 pmol/l and 25 pmol/l. In those cases where serum testosterone concentrations were available at day 1, day 4 and day 22 of the 3 week-hCG test, five cases had a normal serum testosterone at day 4 and three cases only showed such a response by day 22. In those where serum AMH was less than 180 pmol/l, a poor testosterone response of less than 3.5 nmol was observed in approximately seven of eight (88%) cases with a 3-day hCG stimulation test or the 3-week test. An AMH of greater than 180 pmol/l was associated with a normal testosterone response at day 4 in 10 out of 15 (67%) cases and at day 22 in eight of 11 (73%) cases. However, a low serum testosterone concentration of less than 3.5 nmol after the 3-day hCG test was only associated with a likelihood of a low AMH in three of eight (37%) cases. With the 3-week hCG test, a low day 22 testosterone of 9.5 mmol/l or less was associated with a low AMH of 180 pmol/l or less in four of seven (57%) cases., Conclusion: In boys undergoing investigation of gonadal function, the concordance between AMH and testosterone is better at day 22 than day 4. A normal AMH may provide useful information on overall testicular function but does not exclude the need for an hCG stimulation test.
- Published
- 2010
- Full Text
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6. Exaggerated adrenarche in a cohort of Scottish children: clinical features and biochemistry.
- Author
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Paterson WF, Ahmed SF, Bath L, Donaldson MD, Fleming R, Greene SA, Hunter I, Kelnar CJ, Mayo A, Schulga JS, Shapiro D, Smail PJ, and Wallace AM
- Subjects
- Androgens blood, Anti-Mullerian Hormone blood, Birth Weight, Child, Female, Humans, Hyperinsulinism etiology, Infant, Newborn, Male, Ovarian Follicle growth & development, Pelvis diagnostic imaging, Prospective Studies, Ultrasonography, Adrenarche physiology
- Abstract
Objective: To investigate the reported association between exaggerated adrenarche (EA) and reduced foetal growth and to identify possible risk factors for future morbidity in Scottish children with clinical features of EA., Design: Three-year prospective study., Measurements: Auxology, blood pressure (BP), biochemical analysis of blood and urine, pelvic ultrasound in girls., Results: Fifty-two patients were recruited of whom one girl had nonclassical congenital adrenal hyperplasia (17-OHP 17 nmol/l) and one had insufficient blood for analysis. The final cohort comprised 42 girls of mean (SD) age 7.7 (0.99) and eight boys of 8.8 (0.67) years. Mean (SD) birth weight was 3.27 (0.49) and 3.10 (0.76) kg in girls and boys respectively. Height/weight SDS were 1.13/1.69 in girls and 1.69/1.88 in boys. Mean systolic/diastolic BP was 107.8/60.4 (50th-75th centile) in girls and 115.5/63.9 (75th-91st centile) in boys. Uterine and ovarian development was prepubertal. Median serum dehydroepiandrosterone sulphate (DHEAS) was 2.1 and 4.1 mumol/l, androstenedione 3.1 and 3.8 nmol/l in girls and boys respectively, with DHEAS within the reference range/undetectable in 18/2 and androstenedione in 12/6 patients. Fasting insulin was 9.0 and 15.0 mU/l in girls and boys respectively, with concomitant low normal SHBG. Anti-Mullerian hormone (AMH) was 15.7 pmol/l in 27 girls, compared with 5.0 pmol/l in normal girls aged 5-8 years., Conclusions: Our Scottish EA cohort showed female predominance, no evidence of reduced foetal growth, a tendency to overweight with commensurate mild hyperinsulinaemia and modest elevation of serum androgens in some patients. We have found raised AMH levels in the girls, indicating advanced ovarian follicular development.
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- 2010
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7. The role of sex steroids in controlling pubertal growth.
- Author
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Perry RJ, Farquharson C, and Ahmed SF
- Subjects
- Animals, Female, Gonadal Steroid Hormones pharmacology, Growth Hormone blood, Growth Hormone metabolism, Growth Plate growth & development, Growth Plate metabolism, Humans, Insulin-Like Growth Factor I metabolism, Male, Puberty blood, Gonadal Steroid Hormones metabolism, Puberty metabolism
- Abstract
Longitudinal growth, which is primarily due to chondrocytic activity at the level of the epiphyseal growth plate, is influenced by many hormones and growth factors in an endocrine and paracrine manner. Their influence is even more complex during the accelerated growth period of puberty that accounts for about 20% of final adult height. Although abnormalities of growth during puberty are very common, the underlying mechanisms that govern the beginning and cessation of pubertal growth at the level of the growth plate are poorly understood. Sex steroids play a crucial role in pubertal growth both at the systemic level via the GH/IGF-1 axis and at the local level of the epiphyseal growth plate. In both sexes it is now accepted that oestrogen is the critical hormone in controlling growth plate acceleration and fusion. This paper reviews the mechanisms that influence pubertal growth and the problems that are associated with disorders of gonadal function.
- Published
- 2008
- Full Text
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8. Prolonged human chorionic gonadotrophin stimulation as a tool for investigating and managing undescended testes.
- Author
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Dixon J, Wallace AM, O'Toole S, and Ahmed SF
- Subjects
- 17-Hydroxysteroid Dehydrogenases metabolism, Androstenedione blood, Child, Child, Preschool, Cholestenone 5 alpha-Reductase metabolism, Chorionic Gonadotropin administration & dosage, Cryptorchidism metabolism, Dihydrotestosterone blood, Humans, Infant, Male, Retrospective Studies, Sex Hormone-Binding Globulin metabolism, Testis drug effects, Testis pathology, Testosterone blood, Chorionic Gonadotropin therapeutic use, Cryptorchidism diagnosis, Cryptorchidism drug therapy
- Abstract
Objective: To observe the outcome in a group of children with undescended testes (UDT) given prolonged human chorionic gonadotrophin (hCG) stimulation as part of their management., Study Design: Retrospective review of 16 prepubertal boys given intramuscular hCG, 1500 U, on Days 1, 2 and 3 and then twice a week for 2 weeks with assessment of serum testosterone (T), SHBG, dihydrotestosterone (DHT) and androstenedione (A) on Days 1, 4 and 22., Results: In seven boys (44%), peak rise in T was by Day 4; in 5 boys (31%), the rise was by Day 22 and in the remainder, serum T stayed low. The median Day1 testosterone : androstenedione (T : A) ratio rose from 0.4 (range 0.2-1.5) to 1.7 (range 0.2-5.3) at Day 4 (P < 0.05) with no further rise by Day 22. The median dihydrotestosterone : testosterone ratio (DHT : T) at Day 1 and Day 4 remained unchanged. SHBG levels were more likely to be lower at Day 22 than at Day 4. The mean testosterone : SHBG (T : SHBG) ratio as a marker of androgen sensitivity was 0.2 (1SD 0.1). Bilateral testicular descent deemed immediate surgery unnecessary in 3 out of 15 (20%) boys where outcome data were available., Conclusion: Whilst a 3-day hCG stimulation regimen may exclude 17beta-hydroxysteroid dehydrogenase-3 and 5alpha-reductase deficiencies, some boys with cryptorchidism may require more prolonged stimulation to assess androgen production and sensitivity. The possibility that this regimen leads to a reduced need for orchidopexy requires further exploration.
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- 2007
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9. Cytokine profiling and in vitro studies of murine bone growth using biological fluids from children with juvenile idiopathic arthritis.
- Author
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MacRae VE, Wong SC, Smith W, Gracie A, McInnes I, Galea P, Gardner-Medwin J, Farquharson C, and Ahmed SF
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- Adolescent, Animals, Antibodies, Neutralizing pharmacology, Arthritis, Juvenile metabolism, Arthritis, Juvenile physiopathology, Blood Proteins pharmacology, Cell Division physiology, Child, Child, Preschool, Chondrocytes cytology, Chondrocytes immunology, Cytokines metabolism, Female, Growth Disorders metabolism, Growth Disorders physiopathology, Humans, Insulin-Like Growth Factor I metabolism, Male, Metatarsal Bones immunology, Metatarsal Bones metabolism, Mice, Organ Culture Techniques, Synovial Fluid metabolism, Arthritis, Juvenile immunology, Cytokines blood, Growth Disorders immunology, Metatarsal Bones growth & development, Synovial Fluid immunology
- Abstract
Objective: Growth retardation in children with chronic inflammatory disease may be partly due to direct effects of pro-inflammatory cytokines on the growth plate and requires further investigation., Design: This study assessed the cytokine concentrations in serum and synovial fluid (SF) in juvenile idiopathic arthritis (JIA), and determined the effect of the biological fluid on cultured murine metatarsal growth., Patients: Serum and SF were obtained from four children attending for arthrocentesis (child A, systemic; children B, C and D, oligoarticular). In addition, serum samples were obtained from four more children (children E and F, polyarticular; child G, oligoarticular)., Measurements: Anthropometry, cytokine levels and longitudinal bone growth were assessed., Results: Cytokines were elevated to a variable extent in the samples. Although all serum samples were associated with reduced metatarsal growth, only SF from child A and child B reduced metatarsal growth. Metatarsals treated with child A's SF showed reduced proliferation, reduced proliferative and mineralizing zone width, and increased hypertrophic zone width. Tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 concentrations were elevated in child A's SF. However, SF exposure with neutralizing antibodies to these cytokines or IGF-1 did not improve metatarsal growth., Conclusion: SF and serum JIA samples can impair bone growth at the growth plate. In synovial fluid, the effect is variable but resistant to treatment with IL-1beta, IL-6 and TNF-alpha specific antibodies and IGF-1, suggesting that other factors in this biological fluid may also have an effect on longitudinal growth through IGF-1-independent mechanisms.
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- 2007
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10. Congenital adrenal hyperplasia in a Nigerian child with a novel compound heterozygote mutation in CYP11B1.
- Author
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Andrew M, Barr M, Davies E, Wallace AM, Connell JM, and Ahmed SF
- Subjects
- Child, Preschool, Heterozygote, Humans, Male, Nigeria, Adrenal Hyperplasia, Congenital genetics, Mutation, RNA Splice Sites genetics, Steroid 11-beta-Hydroxylase genetics
- Published
- 2007
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11. Undetectable salivary testosterone in young women with premature ovarian failure.
- Author
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Mason A, Wallace AM, Macintyre H, Teoh YP, Bath LE, Critchley HO, Kelnar CJ, Wallace WH, and Ahmed SF
- Subjects
- Adult, Androstenedione blood, Biomarkers analysis, Biomarkers blood, Cross-Sectional Studies, Dehydroepiandrosterone blood, Female, Humans, Ovariectomy, Sex Hormone-Binding Globulin analysis, Statistics, Nonparametric, Testosterone analysis, Testosterone blood, Turner Syndrome metabolism, Primary Ovarian Insufficiency metabolism, Saliva chemistry, Testosterone deficiency
- Abstract
Background: The extent of androgen deficiency in young women with premature ovarian failure (POF) is unclear., Aim: Cross-sectional study of androgen status in young women with POF., Patients: Twenty women with POF: six had Turner syndrome (group A); eight had iatrogenic POF either secondary to bilateral oophorectomy or treatment of malignancy (group B); and six had idiopathic POF (group C). The median age was 30.5 years (range 19-39); in groups B and C the median duration of ovarian failure was 10.0 years (range 1-35)., Methods: After a 2-month wash-out period without sex steroid replacement (SSR), serum testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEAS), SHBG, salivary testosterone (SalT) and the free androgen index [FAI = (serum T/SHBG) x 100] were measured., Results: Median serum A4 was 4.6 nmol/l (10th, 90th centiles, 3.6, 5.1) and DHEAS was 3.2 micromol/l (10th, 90th centiles, 2.3, 9.3). Although median serum T was relatively low at 1.4 nmol/l (10th, 90th centiles, 1.1, 1.7), median SHBG was also low at 34 nmol/l (10th, 90th centiles 22.2, 67.5) and the median calculated FAI was within the normal range at 3.7 (10th, 90th centiles, 2.3, 7.0). However, SalT was undetectable in almost all subjects in the three groups of POF., Conclusions: Serum T and SHBG are relatively low in young women with POF and their FAI is therefore within the normal range. However, SalT, which measures free testosterone, is consistently low to undetectable in these young women with POF. The reliability of the FAI as a marker of androgen deficiency remains questionable.
- Published
- 2006
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12. Short-term effects of prednisolone and dexamethasone on circulating concentrations of leptin and sex hormone-binding globulin in children being treated for acute lymphoblastic leukaemia.
- Author
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Wallace AM, Tucker P, Williams DM, Hughes IA, and Ahmed SF
- Subjects
- Adolescent, Body Mass Index, Child, Child, Preschool, Female, Humans, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma blood, Prospective Studies, Time Factors, Dexamethasone therapeutic use, Glucocorticoids therapeutic use, Leptin blood, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Prednisolone therapeutic use, Sex Hormone-Binding Globulin analysis
- Abstract
Objective: Disturbances in body weight regulation are often encountered during glucocorticoid treatment and are associated with increased insulin resistance and truncal fat accumulation. Children were investigated who were receiving glucocorticoid treatment for acute lymphoblastic leukaemia (ALL). They were randomized to receive either prednisolone or dexamethasone as part of induction of remission. This randomization process provided a suitable opportunity to compare the effects of these two administered steroid on surrogate markers of adipocyte activity (leptin) and hyperinsulinaemia/insulin resistance (SHBG)., Design and Patients: Prospective study over 16 weeks of children randomized to receive prednisolone (40 mg/m2) or dexamethasone (6.5 mg/m2) as part of the MRC-ALL97/99 induction chemotherapy for ALL. Nineteen children (8 male, 11 female) with a median age 5.9 years (range 2.6-13 years) were recruited into the study. Main outcome measures were body mass index (BMI), serum leptin and sex hormone binding globulin (SHBG)., Results: Glucocorticoid administration for 5 weeks resulted in significant (P < 0.05) increases in BMI, leptin (corrected for BMI) and the leptin : SHBG ratio and lowering of SHBG. Dose for dose, dexamethasone was significantly more potent than prednisolone in altering these parameters., Conclusions: Short-term glucocorticoid treatment has significant effects on BMI, leptin and SHBG. The leptin : SHBG ratio increase indicates that this may be a novel and sensitive biochemical marker of metabolic change. Our results suggest that glucocorticoid treatment regimens should be kept as short as possible to avoid possible detrimental effects associated with increased adiposity and insulin resistance.
- Published
- 2003
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13. Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone.
- Author
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Ahmed SF, Tucker P, Mushtaq T, Wallace AM, Williams DM, and Hughes IA
- Subjects
- Adolescent, Alkaline Phosphatase blood, Amino Acids urine, Biomarkers blood, Body Weight drug effects, Bone and Bones enzymology, Child, Child, Preschool, Dexamethasone therapeutic use, Drug Administration Schedule, Female, Glucocorticoids therapeutic use, Humans, Insulin-Like Growth Factor I analysis, Male, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma physiopathology, Prednisolone therapeutic use, Prospective Studies, Bone Remodeling drug effects, Dexamethasone pharmacology, Glucocorticoids pharmacology, Growth drug effects, Prednisolone pharmacology
- Abstract
Aim: To compare the relative potency of prednisolone (Pred) and dexamethasone (Dex) on short-term growth and bone turnover., Method: Prospective study over 16 weeks of children randomized to receive Pred (40 mg/m2) or Dex (6.5 mg/m2) for the first 5 weeks as part of the MRC-ALL97/99 induction chemotherapy for acute lymphoblastic leukaemia (ALL)., Measurements: Lower leg length velocity (LLLV) and weight, serum IGF-I, serum bone alkaline phosphatase (bALP) levels and creatinine-adjusted, urinary excretion of deoxypyridinoline cross-links (DPD)., Subjects: Nineteen children (eight boys, 11 girls) with a median age of 5.9 years (range 2.6-13) and with a diagnosis of ALL., Results: At week 2 of therapy, median LLLV in the Dex group was -1.5 mm/week (range 0.7 to -2.1) and significantly lower than the LLLV in the Pred group which was -0.1 mm/week (range 0.20 to -0.28; P < 0.05). In the Dex group, LLLV remained lower at week 8 (med LLLV, -0.3 mm/week, range 0 to -1.3) compared to LLLV in the Pred group at 0.3 mm/week (range 0.2-1.0; P < 0.05). Body weight showed an increase after week 2 and reached a peak in both groups of children at week 6. The change in weight from baseline was greater in the Dex group than the Pred group reaching a maximum change by week 5 of 17.5% (range 5-25) and 8.7% (range -3 to 18), respectively (P < 0.05). At presentation, median IGF-I level for the whole group was 83.5 micro g/l (range 31.8-293). IGF-I levels fell markedly during Dex therapy and continued to remain lower than baseline. At weeks 4, 6 and 8, median change in IGF-I from baseline was lower in the Dex group than the Pred group. From week 1 to week 3, median change in bALP was 72% (range -8 to 304) in the Pred group, whereas in the Dex group change in bALP was -1% (range 23 to -28; P < 0.005). By week 3, median bALP was higher in the Pred group at 65 U/l (range 36-187) than in the Dex group at 39 U/l (range 26-60; P < 0.05) but by week 6 median bALP in the Pred group had fallen to a similar level to the Dex group. At presentation, median DPD was 22 nmol/l (range 17-38) and 20 nmol/l (range 12-26) in the Pred and Dex groups, respectively (ns), reaching a nadir between weeks 3 and 6. The median percentage change in DPD in the Pred and Dex group from week 1 to week 3 was -34% (range -7 to 14) and -53% (range -6 to -69), respectively (ns). By week 8, DPD excretion had started to rise more dramatically in the Pred group such that the median DPD was 35 nmol/l (range 10-53) in the Pred group and 22 (range 9-30) in the Dex group (P < 0.05). On average, between weeks 2 and 8, LLLV was three times lower, percentage gain in weight was three times higher, bALP was 1.3 times lower and DPD was 1.5 times lower in the Dex group than the Pred group., Conclusion: Pred and Dex both affect short-term growth and bone turnover. The mechanism of the effect on bone formation may be different between the two drugs. Dex may be about 18 times more potent than Pred at suppressing short-term linear growth and stimulating weight gain, and about nine times more potent at suppressing bone turnover. Glucocorticoids have a variable effect on different parameters of growth and bone turnover and the intensity may depend on the steroid used.
- Published
- 2002
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14. GNAS1 mutational analysis in pseudohypoparathyroidism.
- Author
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Ahmed SF, Dixon PH, Bonthron DT, Stirling HF, Barr DG, Kelnar CJ, and Thakker RV
- Subjects
- Adolescent, Adult, Child, Child, Preschool, DNA Mutational Analysis, Female, Frameshift Mutation, Humans, Male, Mutation, Missense, Pedigree, Polymorphism, Single-Stranded Conformational, Protein Isoforms, DNA genetics, GTP-Binding Protein alpha Subunits, Gs genetics, Pseudohypoparathyroidism genetics
- Abstract
Objective: Mutations of the GNAS1 gene, which is located on chromosome 20q13.11 and encodes the alpha-subunit of the stimulatory GTP-binding protein, have been identified in patients with pseudohypoparathyroidism type Ia (PHPIa) and pseudopseudohypoparathyroidism (PPHP). We have undertaken studies to determine the prevalence of GNAS1 mutations and to explore methods for their more rapid detection., Methods: Thirteen unrelated families (8 with PHPIa and PPHP patients, and 5 with PPHP patients only) were investigated for GNAS1 mutations in the 1050 base-pair (bp) region spanning exons 2-13 by single-stranded conformational polymorphism (SSCP) and DNA sequence analysis., Results: GNAS1 mutations were detected in 4 of the 8 families with PHPIa patients. These consisted of: two novel de novo missense mutations (Pro115Ser and Glu259Val) in two families and an identical 4 bp deletion of codons 189 and 190 resulting in a frame-shift in two unrelated families. These results expand the spectrum of GNAS1 mutations associated with this disorder and confirm the presence of a mutational hot-spot involving codons 189 and 190. SSCP analysis was found to be a specific and sensitive method that detected all 4 mutations. GNAS1 mutations were not detected in any of the PPHP only families., Conclusions: The pseudohypoparathyroid disorders appear to represent a heterogeneous group with GNAS1 mutations forming the molecular aetiology in approximately 50% of pseudohypoparathyroidism type Ia families. Such mutations can be reliably identified by single-stranded conformational polymorphism and this will help to supplement the clinical evaluation of some patients and their families, particularly as the disease may not be fully penetrant.
- Published
- 1998
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