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Biomedical subjects

A M Wallace

Publications and source records attributed to A M Wallace.

At least 19 recordsLinked to original sources
PubMed2026

Surgical Management of Young Women with High-Risk Breast Cancer Receiving Neoadjuvant Systemic Therapy on the I-SPY2 Trial.

BACKGROUND: Mastectomy rates in women with breast cancer are higher in younger women than in older women. The impact of this more extensive surgery on overall survival (OS) and locoregional recurrence in younger women is unknown, especially after neoadjuvant systemic therapy (NST). This study evaluated surgical management and outcomes of patients aged &#x2264; 45 versus > 45 years enrolled in multicenter NST clinical trial, I-SPY2.0 (NCT01042379, PMID 37325931). METHODS: We conducted a secondary data analysis comparing locoregional treatment in patients aged &#x2264; 45 versus > 45 years with clinical or molecular high-risk clinical stage II-III breast cancer treated from April 2010 to June 2022. Multivariate Cox proportional hazards models were used to evaluate associations between type of breast surgery with OS and locoregional recurrence-free interval by age group and tumor receptor subtype. RESULTS: Of 1737 patients, 698 (40.2%) were aged &#x2264; 45 years. There were no significant differences in patient or tumor characteristics or residual cancer burden distribution between age groups. Although breast-conserving surgery was significantly less common in younger women (36.8% vs 48.5%, p < 0.001), surgery type was not associated with OS or locoregional recurrence-free interval for patients aged &#x2264; 45 years. CONCLUSIONS: Greater extent of breast surgery was not associated with improved outcomes in women aged &#x2264; 45 years. Choice of surgical procedure in the management of breast cancer is multifactorial, but young age alone&#xa0;does not warrant mastectomy following NST.

Breast cancer↗
PubMed2006

Undetectable salivary testosterone in young women with premature ovarian failure.

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.

Adult↗
PubMed2006

Stability of housekeeping genes in alveolar macrophages from COPD patients.

The stability of housekeeping genes is critical when performing gene expression studies. To date, there have been no studies that look at the stability of commonly used housekeeping genes in alveolar macrophages. Expression levels may be affected by culture, stimulation or disease severity. The present study investigated the expression level of 10 housekeeping genes and analysed the stability of their expression in alveolar macrophages from chronic obstructive pulmonary disease patients (n = 22) who were classified according to disease severity. Guanine nucleotide-binding protein, beta polypeptide 2-like 1 (GNB2L1), hypoxanthine phosphoribosyl transferase 1 (HPRT1) and ribosomal protein L32 (RPL32) were the most stably expressed in alveolar macrophages, irrespective of disease severity. There was no difference in the expression levels of 10 housekeeping genes between mild and moderate/severe patients. GNB2L1, HPRT1 and RPL32 were also stably expressed in alveolar macrophages cultured with no stimulation, or with interleukin-1beta, lipopolysaccharide or tumour necrosis factor-alpha stimulation. In conclusion, as fluctuations in the expression of some housekeeping genes were observed, including glyceraldehyde-3-phosphate dehydrogenase, it is recommended that guanine nucleotide binding protein, beta polypeptide 2-like 1 be used as a reference gene for alveolar macrophages in similar study designs, or that the stability of housekeeping genes be validated in alveolar macrophages prior to expression studies.

Aged↗
PubMed2005

The utility of three different methods for measuring urinary 18-hydroxycortisol in the differential diagnosis of suspected primary hyperaldosteronism.

OBJECTIVE: Urine 18-hydroxycortisol (18-OHF) measurements are claimed to discriminate between primary hyperaldosteronism due to Conn's syndrome/adrenal adenoma or idiopathic bilateral adrenal hyperplasia (BAH), and also to identify cases of glucocorticoid-suppressible hyperaldosteronism (GSH). We have evaluated three urine 18-OHF methods using a panel of urine samples from patients with hypertension. DESIGN: Clinical methods comparative study. METHODS: Urine samples from patients with primary hyperaldosteronism due to either adenoma (n = 6), BAH (n = 6), GSH (n = 9), or essential hypertension (n = 38) were analysed without knowledge of the diagnosis using three different methods in different laboratories. These included 'in-house' radioimmunoassay (RIA), 'in-house' time-resolved fluorometric assay (DELFIA), and gas chromatography mass spectrometry (GC-MS). RESULTS: The three assays showed good correlation, but there were large bias differences: RIA bias was greater than DELFIA which was greater than GC-MS. Discrimination between adenoma and BAH patients was best for the DELFIA method, with no overlap between results for these two groups. All three methods gave significantly elevated results for the GSH group compared with the BAH and essential hypertension groups. No assay distinguished BAH from essential hypertension. CONCLUSION: Measurement of urine 18-OHF may be a useful additional test in the differential diagnosis of primary hyperaldosteronism. The clinical diagnostic value of urinary 18-OHF measurements is method-dependent with the DELFIA assay having the best discriminatory value.

Adenoma↗
PubMed2004

The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer.

The relationship between circulating C-reactive protein concentrations and potential cytokine and receptor mediators (interleukin-6, leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), soluble IL-6 receptor, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and interleukin-8 (IL-8)) of this acute phase protein were examined in healthy subjects (n=11) and patients with non-small-cell lung cancer (n=50). Leukaemia inhibitory factor and CNTF were below detection limits in all controls and patients. C-reactive protein, interleukin-6, soluble gp130, soluble TNF receptor, interleukin-1 receptor antagonist and IL-8 concentrations were significantly elevated in cancer patients (P< or =0.001). Cancer patients with elevated C-reactive protein concentrations had greater concentrations of interleukin-6 (P<0.01) and interleukin-1 receptor antagonist (P<0.05). On regression analysis only interleukin-6 was independently associated with C-reactive protein (r=0.616, P<0.001). Interleukin-6 is an important independent mediator of elevated C-reactive protein concentrations in patients with non-small-cell lung cancer.

Adult↗
PubMed2004

The relationship between interleukin-6 and C-reactive protein in patients with benign and malignant prostate disease.

The relationship between interleukin-6 and C-reactive protein was evaluated in patients with benign (n=59) and malignant (n=86) prostate disease. The correlation coefficients for patients with benign prostatic disease and prostate cancer were rs=0.632, P<0.001 and rs=0.663, P<0.001, respectively. These results indicate that the relationship between interleukin-6 and C-reactive protein is similar in patients with benign and malignant prostate disease.

Aged↗
PubMed2004

The response of leptin, interleukin-6 and fat oxidation to feeding in weight-losing patients with pancreatic cancer.

At baseline, weight-losing pancreatic cancer patients (n=7) had lower leptin (P<0.05) but higher cortisol, interleukin-6, resting energy expenditure and fat oxidation than healthy subjects (n=6, P<0.05). Over a 4 h feeding period, the areas under the curve for glucose, cortisol and interleukin-6 were greater (P<0.05), but less for leptin in the cancer group (P<0.05). Therefore, it would appear that low leptin concentrations, increased fat oxidation and insulin resistance are associated with increased concentrations of cortisol and interleukin-6 in weight-losing patients with pancreatic cancer.

Blood Glucose↗
PubMed2004

Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins.

OBJECTIVE: The precise interactions between glucocorticoids and leptin are complex and poorly understood. The aim of the study was to investigate whether the glucocorticoid/leptin interaction is influenced by shared environmental or genetic factors. DESIGN: We investigated the heritability of body mass index (BMI), circulating leptin and urinary glucocorticoid metabolites [tetrahydrocortisol (THF), alloTHF and tetrahydrocortisone (THE)] in 54 monozygotic (MZ) and 39 dizygotic (DZ) female twins. Analysis was performed using a structural equation modelling package Mx, developed by Neale. RESULTS: Leptin and BMI showed substantial heritability (68.3% and 71.3%, respectively). Bivariate analysis indicated that the genetic determinants of BMI and leptin are partly shared. Total cortisol metabolites (THF + alloTHF + THE), the (THE + alloTHF)/THE ratio [a marker of 11beta-hydroxysteroid dehydrogenase (11HSD) activity] and the alloTHF/THF ratio (marker for 5alpha-reductase activity) followed an environmental pattern. The heritability of leptin was significantly lowered to 63.8% (P = 0.012) when values were corrected for the influence of total cortisol metabolites but unaffected by markers of 11HSD and 5alpha-reductase activity. CONCLUSIONS: We confirm that the genetic influence on both BMI and the circulating leptin concentration is substantial and show that these genetic determinants are highly correlated. These genetic factors, which are more likely to be dominant than additive, can be modestly but significantly modified by urinary total cortisol metabolites implying an adrenal influence.

Adult↗
PubMed2004

Testosterone measurements in early infancy.

Circulating testosterone concentrations in infants measured by a direct chemiluminescent immunoassay (Bayer ADVIA Centaur) were compared with those measured by a traditional radioimmunoassay using solvent extraction. The results confirm that neonatal circulating testosterone concentrations are method dependent, and each laboratory should establish method related reference ranges especially if using a direct commercial immunoassay. The results indicate that the Bayer ADVIA Centaur procedure can be used reliably in neonates. Expected values for male and female infants < 10 days old were 2.5-11.1 (n = 36) and 1.7-5.6 (n = 36) nmol/l respectively. For older neonates (10-50 days) the ranges were 0.2-17.2 (n = 42) and 0.1-1.5 (n = 7) nmol/l respectively.

Age Factors↗
PubMed2004

Nocturnal secretory dynamics of inhibin B and testosterone in pre- and peripubertal boys.

To investigate the secretory dynamics of testosterone and inhibin B, we collected samples every 20 min from 2000 h to 0800 h in 20 boys. Boys in group 1 (n = 5) were aged less than 8 yr, group 2 (n = 5) were aged more than 8 yr but 1.5 yr or more before pubertal onset, group 3 (n = 5) were studied 1.0 yr or less before pubertal onset, and group 4 (n = 5) were in early puberty. Testosterone increased after midnight in peripubertal boys, coinciding with the onset of LH pulsatility, and showed a pulsatile pattern in 6 of 10 of these boys. Cross-correlation analysis indicated significant temporal coupling between LH and testosterone. Inhibin B was higher in groups 3 and 4, compared with groups 1 and 2 (P < 0.01) and showed a downward trend overnight with no evidence of pulsatility and no evidence of short-term interactions with LH, FSH, or testosterone. Inhibin B and LH nocturnal means were both inversely correlated with time before pubertal onset (r(s) > or = -0.85, P < 0.01). Only LH nocturnal mean and amplitude, respectively, contributed independently to prediction of testosterone and inhibin B nocturnal means, explaining 71 and 65% of their variability. We conclude that both testosterone and inhibin B are related to nocturnal LH release in peripubertal boys but over different time scales.

Adolescent↗
PubMed2004

Transdermal testosterone application: pharmacokinetics and effects on pubertal status, short-term growth, and bone turnover.

The aim of the study was to assess the effect of transdermal testosterone on free testosterone concentrations in saliva and on short-term growth and bone turnover in boys with growth or pubertal delay. A prospective, randomized, crossover study was conducted over 26 wk with 4 wk of run-in, 8 wk of treatment I (8 or 12 h), 4 wk of washout, 8 wk of treatment II (8 or 12 h), and 4 wk of final washout. The main outcome measures were salivary testosterone profiles during the different study periods; weekly change in lower leg length (LLL) as measured by knemometry, i.e. LLL velocity; absolute and percentage change in bone alkaline phosphatase (bALP) levels; and deoxypyridinoline cross-links measured in urine. Eight boys who took part in the study had a median age of 13.5 yr (range, 12.4-14.9 yr), testicular volume of 3 ml (range, 2-6 ml), height SD score of -2.4 (range, -1.44 to -3.35), and bone age delay of 2 yr (range, 1-3.2 yr). Median salivary testosterone during 8- and 12-h treatments [179 pg/ml (range, 7-3579 pg/ml) and 150 pg/ml (range, 12-3472 pg/ml) (not significant)] was significantly higher than during the run-in and washout blocks (P < 0.0001) [9 pg/ml (range, <7 to 122 pg/ml) and 13 pg/ml (range, <7 to 285 pg/ml) (not significant)]. LLL velocity in the treatment blocks (median, 0.64 mm/wk; range, 0.1-1.08 mm/wk) was significantly higher than during the run-in and washout periods (median, 0.48 mm/wk; range, -0.06 to 0.92 mm/wk) (P < 0.001). The main rise in bALP occurred during the first treatment block with a median percentage change in bALP of 44.2% (range, -4 to 87%) and a smaller percentage change in bALP at the end of the second treatment block of 9.8% (range, -4 to 55%). The increases in bALP were not significantly different between the 8- and 12-h treatment periods, and there was no significant decline during the washout periods. Overnight transdermal testosterone application, as Virormone (5 mg), may be a potentially acceptable method of induction of puberty and stimulates short-term growth and bone turnover.

Administration, Cutaneous↗
PubMed2004

Comparison of total, complexed and free prostate-specific antigens and their ratios in the detection of prostate cancer in a non-screened population.

BACKGROUND: The role of prostate-specific antigen (PSA) isoforms in the detection of prostate cancer in a non-screened population in the UK remains to be determined. METHODS: Consecutive patients undergoing diagnostic transrectal ultrasound-guided biopsy of the prostate were studied. Prior to biopsy, a blood sample was obtained and total, complexed and free PSA concentrations measured. RESULTS: Of the 171 patients included in the study, 103 were found to have prostate cancer. There were significant differences in total and complexed PSA concentrations and in the ratio of free-to-total PSA (all P <0.001) between patients with prostate cancer and those with benign disease. Receiver operating characteristics (ROC) curve analysis showed that the corresponding areas under the curves were similar. Restricting the analysis to the 77 patients who had total PSA concentrations between 2 and 10 micro g/L, ROC curve analysis showed that total and complexed PSA concentrations failed to discriminate between benign and malignant disease. In contrast, the areas under the ROC curve were greater for the free-to-total ratio (P = 0.033). CONCLUSION: These results show that in patients with total PSA concentrations between 2 and 10 micro g/L, the free-to-total PSA ratio was superior to total PSA concentration in discriminating between patients with benign and malignant disease.

Biomarkers↗
PubMed2004

Randomized, crossover comparison study of the short-term effect of oral testosterone undecanoate and intramuscular testosterone depot on linear growth and serum bone alkaline phosphatase.

AIM: To compare the effects of oral testosterone undecanoate (TU) 40 mg daily and intramuscular depot sustanon 50 (SUS), 4 weekly, on short-term growth and bone turnover. METHOD: Prospective, randomised, cross-over study over 26 weeks with 4 weeks of run-in, 8 weeks of treatment I (TU/SUS), 4 weeks of wash-out, 8 weeks of treatment II (SUS/TU) and 4 weeks of final wash-out. MAIN OUTCOME MEASURES: Weekly change in lower leg length (LLL) as measured by knemometry, i.e. LLL velocity (LLLV) and absolute bone alkaline phosphatase levels (bALP), as well as percentage change in bALP (%bALP). PATIENTS: Fourteen boys with delayed growth and puberty; two declined and one boy with sickle cell trait dropped out with priapism a week after SUS. The remainder had a median age of 14.3 years (range 12.5-17.4), testicular volume of 2 ml each (2-6), HtSDS of -2.1 (-3.3 to -1.0) and BA delay of 2.4 years (0.7-4.4). RESULTS: Median LLLV in the treatment blocks was 0.7 mm/wk (-0.27 to 2.2) and LLLV during the run-in and wash-out periods was 0.27 mm/wk (-0.3 to 0.6) (p <0.005). LLLV during treatment with TU and SUS was 0.51 mm/wk (-0.22 to 2.17) and 0.67 mm/wk (-0.27 to 2.2), respectively (NS). Median LLLV during the washout phases that followed the TU block and the SUS block was similar at 0.28 mm/wk (-0.1 to 0.6) and 0.3 mm/wk (-0.2 to 0.6), respectively. LLLV peaks and troughs that were related to the timing of the injection were more evident during SUS therapy. Median bALP during the run-in period was 94.2 U/l (16-282) and the median %bALP during this period was 1.2% (-57, 16). The main rise in bALP occurred during the treatment blocks with a %bALP of 19.3% (-28.8, 121.7) (p <0.005). Median bALP at the beginning and end of the SUS block was 99.7 U/l (51.7, 225) and 170 U/l (64.8, 273), respectively (p <0.05). Median bALP at the beginning and end of the TU block was 111 U/l (51, 287) and 127.6 U/l (66.4, 298) (NS). Median %bALP during SUS was higher than during TU at 28.1% (4.4, 121.7) and 11.8% (-28.8, 83.6) (p = 0.07). CONCLUSION: At the doses studied, testosterone undecanoate was as effective as sustanon at promoting short-term growth but changes in bone alkaline phosphatase were more marked during sustanon therapy.

Administration, Oral↗
PubMed2003

Moderate physical activity permits acute coupling between serum leptin and appetite-satiety measures in obese women.

OBJECTIVES: To investigate whether moderate physical activity or snack intake influence appetite sensations and subsequent food intake in obese women. Associations between serum leptin and appetite ratings were also investigated. METHODS: In all, 10 obese women (mean age+/-s.d.: 50.0+/-8.5 y; mean body mass index (BMI)+/-s.d.: 37.2+/-6.5 kg m(-2)) were submitted in random order to three trials: Moderate physical activity (20 min brisk walking), Snack (58.5 g chocolate-based) and Control (sitting, TV-watching). Appetite and satiety were assessed by visual analogue scales, and serum leptin, blood glucose and plasma free fatty acids were measured at baseline, pre- and postintervention and 1 h postintervention (ie, before dinner). A buffet-style dinner was provided subsequent to the three trials. RESULTS: The moderate physical activity and snack intake both produced lower appetite and higher satiety and fullness perceptions, compared to control, following the intervention. No significant differences were found in subsequent food intake. Serum leptin concentrations did not differ between trials. Serum leptin was not associated with appetite or satiety sensations at any time during the control or the snack trials, but was correlated following moderate physical activity (prospective food consumption r(s)=-0.83, P=0.003; hunger r(s)=-0.79, P=0.007; desire to eat r(s)=-0.69, P=0.02; satiety r(s)=0.71, P=0.02; fullness r(s)=0.66, P=0.04). These associations were not influenced by BMI or fat mass. CONCLUSIONS: Moderate physical activity and snack intake suppress the appetite of obese women acutely. The associations between circulating leptin and appetite-satiety ratings suggest leptin involvement in short-term appetite regulation in response to physical activity-induced factors.

Adult↗
PubMed2003

Gender variation in leptin circadian rhythm and pulsatility in adult growth hormone deficiency: effects of growth hormone replacement.

OBJECTIVES: Adult growth hormone deficiency (AGHD) is characterized by obesity and associated with increased leptin concentration and decreased leptin pulsatility. Growth hormone replacement (GHR) results in a decrease in leptin concentration and increase in leptin pulsatility, followed by reduction in body fat mass (BFM). In both health and AGHD, women exhibit relatively higher leptin concentrations compared to men. The effect of gender on leptin rhythm and pulse parameters in AGHD is yet to be defined and the gender difference in the response of leptin secretory pattern to GHR has not been determined. Therefore the aim of this study was to evaluate the effect of gender on circadian and pulse parameters of leptin secretion in AGHD, and examine the gender variation in response of these parameters to GHR. STUDY DESIGN: A prospective, open treatment design study to determine the effect of gender on leptin rhythm and pulse parameters in untreated and treated AGHD. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 2-weekly intervals to achieve and maintain IGF-I SDs between the median and upper end of the age-related reference range. PATIENTS: Twelve patients (six men, six women) with severe AGHD following pituitary surgery, defined as peak GH response < 9 mU/l to provocative testing were studied. All patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Plasma leptin was measured at half-hourly intervals for 24 h, before and 1 month after initiation of GHR. Cosinor analysis was used to determine the circadian rhythm parameters: MESOR (rhythm-adjusted mean), acrophase and amplitude; and ULTRA algorithm used for pulse analysis. Body composition was measured using bioelectrical impedance. RESULTS: BFM was higher in women than men at both visits (P < 0.05), but there was no significant change in BFM in either gender following 1 month of GHR. Women had a higher mean 24-h leptin concentration, MESOR, circadian amplitude and pulse amplitude, both before and after GHR (P < 0.05). Following treatment, mean leptin concentration and MESOR decreased significantly in both men and women (P < 0.05), with no significant difference in percentage change between the genders. Pulse frequency increased and duration decreased significantly after GHR in both groups, without any significant gender difference. IGF-I and IGF SDs were similar in both genders at baseline (P = 0.93). However, after 1 month GHR, the increase in both measurements was greater in men than women (P = 0.005) and men had significantly higher IGF-I and IGF SDs than women (P = 0.01). CONCLUSIONS: As in healthy individuals, leptin levels were higher in women with AGHD than men, both prior to and after GHR. Decline in leptin concentrations and increase in leptin pulsatility following 1 month of GH treatment were similar in both genders. Changes in leptin secretory parameters appeared to occur without any significant decrease in BFM, suggesting a regulatory role for GH. Additionally, the action of GH on leptin secretory pattern does not appear to be mediated by IGF-I. Our data suggest that changes in leptin concentration and rhythm parameters following GHR are independent of gender.

Adult↗
PubMed2003

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.

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.

Adolescent↗