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Biomedical subjects

O D Wolthers

Publications and source records attributed to O D Wolthers.

At least 19 recordsLinked to original sources
PubMed2006

Short-term growth and adrenal function in children with asthma treated with inhaled beclomethasone dipropionate hydrofluoroalkane-134a.

Inhaled beclomethasone dipropionate (BDP) with the propellant hydrofluoroalkane-134a (HFA) has been designed to be equivalent in terms of safety to chlorofluorocarbon (CFC)-formulated metered dose inhalers (MDI). The aim was to assess whether BDP HFA MDI 100 microg twice daily was equivalent to BDP CFC MDI 100 microg twice daily in terms of effects on short-term lower leg growth rate (LLGR) and measures of hypothalamic-pituitary-adrenal (HPA) function. The study consisted of a randomized double-blind cross-over trial with three active, a run-in and two wash-out periods each consisting of 2 wk. The place of study was a secondary referral outpatient clinic. The subjects involved were 14 boys and 10 girls with asthma, aged 7-12 yr. They were all administered BDP HFA 100 microg, BDP CFC 100 microg and 200 microg twice daily. The outcome measures included LLGR and 24-h urine-free cortisol (UFC) and total cortisol metabolites (TCM). Mean (SD) LLGR during run-in and BDP HFA 100 microg, BDP CFC 100 microg and 200 microg twice daily periods were 0.43 (0.23), 0.09 (0.29), 0.10 (0.45) and 0.08 (0.27) mm/wk. The one-sided 97.5% confidence interval for the difference in LLGR between BDP HFA 100 microg and BDP CFC 100 microg was 0.24, thus, below the predefined criterion of 0.20 mm/week. Inter-period comparisons of active treatments showed no differences between means of LLGR, UFC or TCM. Though non-inferiority between BDP HFA and CFC 100 microg twice daily in terms of effects on LLGR was not found, equivalence was suggested by comparisons of LLGR during run-in and active treatments and by HPA function measures.

Administration, Inhalation↗
PubMed2006

A questionnaire on factors influencing children's assent and dissent to non-therapeutic research.

BACKGROUND: Knowledge about assent or dissent of children to non-therapeutic research is poor. OBJECTIVES: To assess sociodemographic characteristics in healthy children and adolescents who were invited to participate in non-therapeutic research, to evaluate their motives for assent or dissent and their understanding of the information given. METHODS: A total of 1281 healthy children and adolescents six to sixteen years of age were invited to participate in a non-therapeutic study and a questionnaire. RESULTS: Assenting children were motivated by a desire to help sick children (n = 638, 98%) and to gain experience with participating in a research study (n = 503, 82%). Dissenting children made their decision because of worries about having a blood (n = 193, 46%) or a urine sample (n = 94, 26%) taken or because of worries about a doctor's examination (n = 136, 33%). Fewer children in the assent group (n = 166, 25%) than in the dissent group (136, 33%) worried about the doctor's examination (p = 0.01). In the assent and dissent group, 568 (86%) and 343 (85%) children, respectively, said they were able to understand some or all of the written information (p = 0.42), and 650 (97%) and 330 (98%), respectively, were able to understand some or all of the verbal information (p = 0.07). CONCLUSIONS: Sociodemographic characteristics may not influence healthy children's decision to volunteer for non-therapeutic research. Assenting children have altruistic and educational motives, whereas worries about procedures may cause children to dissent. A great majority of school children and adolescents feel capable of understanding and giving assent or dissent to non-therapeutic research.

Adolescent↗
PubMed2004

Assessment of the relation between short and intermediate term growth in children with asthma treated with inhaled glucocorticoids.

OBJECTIVE: To assess the relation between short-term growth and intermediate term growth in children with asthma treated with inhaled glucocorticoids. DESIGN: An open 12 months parallel group trial with visits to the clinic on day 1, after 2, 4, 8, 12, 20, 28, 36, 44 and 52 weeks. SETTING: Outpatient clinic in a secondary referral centre. SUBJECTS: Sixteen children with asthma aged 9 (6-13) years; 16 matched healthy subjects. METHODS: Knemometry and stadiometry. INTERVENTIONS: Dry-powder inhaled budesonide 200 microg twice daily. PRIMARY OUTCOME MEASURES: Intra-group comparisons of mean lower leg growth rates. SECONDARY OUTCOME MEASURES: Inter-group comparisons of mean lower leg growth rates and intra-group comparisons of mean height-standard deviation scores. RESULTS: One year mean lower leg growth rate (0.36 mm/week) did not differ from the rates during the 2 (0.27 mm/week; P = 0.23), 4 (0.33 mm/week; P = 0.54), 8 (0.36 mm/week; P = 0.79) or 12 (0.33 mm/week; P = 0.49) weeks intervals in the asthma group. Similarly, in the healthy children 2 (0.56 mm/week; P = 0.63), 4 (0.46 mm/week; P = 0.36), 8 (0.43 mm/week; P = 0.49) and 12 (0.43 mm/week; P = 0.66) weeks mean growth rates did not vary statistically significantly from the 1 year growth rate (0.42 mm/week). Mean lower leg growth rates, however, were consistently lower during all periods in the children with asthma (P = 0.02-0.03). At completion of the study mean height-standard deviation score in the asthma group (-0.19) was significantly suppressed as compared with the score at study entry (-0.03) (P = 0.02), whereas no statistically significant variation was detected in the control group. CONCLUSIONS: Short-term lower leg growth rates are consistent with intermediate term growth rates in group studies in children with asthma treated with inhaled dry powder budesonide 400 microg/day. Short-term group knemometry should be an integral part of growth evaluations of new inhaled glucocorticoids, doses and inhalation devices in children with asthma.

Administration, Inhalation↗
PubMed2004

Methodological aspects of high-frequency ultrasound of skin in children.

BACKGROUND: High-frequency ultrasound of the skin has recently been introduced for assessment of systemic effects in the cutis and subcutis of oral and inhaled glucocorticoids in children. However, the use of high-frequency skin ultrasound in clinical trials is invalidated because important methodological aspects have not been addressed. The aim of the present study was to evaluate inter- and intraobserver, day to day and diurnal variations of measurement of thickness of cutis and subcutis, and the fraction of low echogenic pixels (fLEP) in the cutis and, furthermore, to assess effects of exercise on the cutis and subcutis and variations in subcutaneous thickness between anatomical locations in children with a high-frequency B-mode ultrasound scanning device. METHODS: Three studies were conducted, each including 10 healthy prepubertal children. High-frequency skin ultrasound was performed with the 20 MHz Dermascan C (Cortex Technology, Hadsund, Denmark). In study 1, the same observer performed five consecutive scannings to assess intraobserver variations. In study two different observers performed scannings at 2 h intervals between 08:00 and 20:00 h, whereby interobserver and diurnal variations were assessed. In study 3, the same observer performed scannings in different anatomical locations on five consecutive days, and on one of these days before and after exercise. Thus day-to-day variations and the effect of exercise were assessed. RESULTS: Low inter- and intraobserver variations were found on assessment of the thickness of cutis and subcutis, whereas high variations were found on evaluation of the dermal water content. Diurnal variations were absent, and day-to-day variations were low. Exercise caused significant increases in the thickness of cutis and subcutis on the thigh. CONCLUSION: Low inter- and intraobserver variations make high-frequency ultrasound a precise and reliable tool for assessment of the cutaneous and subcutaneous thickness in children. In future trials, repetitive scannings need not to be performed at the same time of the day, whereas strenuous physical activity should be avoided on days of examination.

Body Water↗
PubMed2004

Lower leg growth suppression caused by inhaled glucocorticoids is not accompanied by reduced thickness of the cutis or subcutis.

BACKGROUND: Exogenous glucocorticoids suppress short-term lower leg growth in children as assessed by knemometry. The knemometric measurements, however, may be confounded by reductions in the thickness of the cutis and subcutis over the knee. AIM: To assess whether inhaled glucocorticoid-induced suppression of short-term growth is accompanied by changes in the thickness of the cutis and subcutis. METHODS: The study was a randomized, controlled, crossover trial with 1 wk treatment, run-in and washout periods. Active treatment was inhaled budesonide 200 microg twice daily. Short-term growth was assessed by knemometry, and the thickness of the cutis and subcutis over the knee, on the volar forearm and abdomen was measured by 20 MHz B-mode ultrasound. MATERIAL: Nineteen children with asthma aged 7 to 13 y. RESULTS: Lower leg growth was significantly reduced during budesonide treatment (0.27 mm/wk) compared to the treatment-free period (0.54 mm/wk) (p = 0.02, 95%: -0.50 to -0.05). Variations in the thickness of the cutis were seen during budesonide treatment (mean +/- SEM): -0.01 +/- 0.03 mm over the knee, -0.02 +/- 0.02 mm on the forearm and 0.01 +/- 0.02 mm on the abdomen. The variations in the total thickness of the cutis and subcutis were -0.05 +/- 0.12 mm, 0.06 +/- 0.12 mm and -0.06 +/- 0.10 mm during budesonide treatment. The variations in thickness of the cutis or subcutis were not statistically different during budesonide treatment and the treatment free period in any anatomical location. CONCLUSIONS: Short-term lower leg growth suppression induced by inhaled glucocorticoids is not confounded by variations in thickness of cutis or subcutis. The present observations further establishes knemometry as a reliable tool for assessment of the risk of growth suppression of inhaled glucocorticoids in children with asthma.

Abdomen↗
PubMed2003

Eosinophil granule proteins in the assessment of airway inflammation in pediatric bronchial asthma.

Eosinophil granule proteins such as eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil protein X (EPX) in serum and urine are indirect measures of eosinophil activity. The measures have been evaluated for prediction, diagnosis and monitoring of anti-inflammatory treatment modalities in children with asthma. Assessments in serum and urine are highly dependent on sampling procedures and must be performed under strictly controlled conditions using standardized sampling and laboratory procedures. The measures are influenced by circadian and seasonal variations. Measurement of the eosinophil granule proteins does not improve the predictive value of a family history of atopy. Due to insufficient sensitivity and specificity, the measures are not useful in the diagnosis of asthma in children, and the clinical use of eosinophil proteins in the individual child for assessment of asthma severity has not been sufficiently validated. Serum and urine eosinophil granule proteins, however, may be useful in extending our knowledge of suppressive effects on eosinophil activity of various doses, devices and administration regimens of inhaled glucocorticoids in children. Such evaluations may be performed in randomized, double-blind trials of well-defined age groups and they should include measures of compliance. One important aspect to look at would be the distinction between suppressive effects on eosinophil activity and clinically important anti-inflammatory effects. Considering the complexity of airway inflammation and the heterogeneity of childhood asthma, however, it may be too simplistic to look for a single measure of the inflammatory processes. In the future, perhaps, a combination of products of inflammatory cells may give more clinically relevant information with respect to prediction, diagnosis, monitoring and outcome of childhood asthma.

Anti-Inflammatory Agents↗
PubMed2003

Circadian variations in serum eosinophil cationic protein, and serum and urine eosinophil protein X.

Biochemical evaluation of inflammation may be a useful adjunct to measures of pulmonary function and symptoms in children with asthma. However, little data have been provided to validate the markers in children. The aim of the present study was to assess circadian variations in serum eosinophil cationic protein (ECP), and serum and urine eosinophil protein X (EPX) in children. Five girls and two boys aged 10-14 years were studied. The first sample of urine consisted of urine collected from 24.00 hours the night before until 08.00 hours on the morning of the day of investigation. Thereafter urine was collected at 4-h intervals until 24.00 hours and in another 8-h interval from 24.00 to 08.00 hours. Blood samples for assessment of serum ECP and serum EPX were collected every 2 h during the 24 h. Statistically significant circadian variations in serum ECP (F=3.2, p=0.002), serum EPX (F=3.1, p=0.002) and in urine EPX/creatinine (F=5.4, p=0.003) were detected. The concentrations were higher during the night compared to daytime. Peak levels of serum ECP (mean [+/- SEM]) were found at 06.00 hours (16.3 [5.3] micro g/l), trough levels at 08.00 hours (3.9 [0.7] micro g/l) (p=0.01). Peak levels of serum EPX were seen at 06.00 (43.7 [9.5] micro g/l) with trough levels at 12.00 hours (22.0 [3.5] micro g/l) (p=0.01). Peak levels of urine EPX/creatinine occurred in urine collected from 24.00 to 08.00 hours (90.0 [27.7] micro g/mmol), trough levels in the 16.00-20.00 hours sample (29.7 [8.9] micro g/mmol) (p=0.02). Serum ECP, serum EPX and urine EPX exhibit a circadian variation in children with nocturnal and early morning peak levels. To avoid confounding influence from circadian variations in ECP and EPX in clinical studies blood or urine should be sampled at consistent times.

Adolescent↗
PubMed2003

Ultrasound of skin in prednisolone-induced short-term growth suppression.

OBJECTIVE: To assess the thickness of the cutis and subcutis in children with prednisolone-induced knemometric growth suppression. DESIGN: A double blind, placebo-controlled crossover trial with two 7-day treatment periods. PATIENTS: Twenty children with asthma aged 7.7 to 13.8 (mean 10.4) years. INTERVENTIONS: 5 mg prednisolone/day. OUTCOME MEASURES: Lower leg growth rate, thickness of cutis and subcutis and the fraction of low echogenic pixels determined by ultrasound. RESULTS: Mean lower leg growth rate was -0.23 during prednisolone, 0.58 mm/week during placebo treatment (p < 0.01). Mean total thickness of cutis and subcutis over the knee was reduced by 0.28 during prednisolone, increased by 0.07 mm/week during placebo treatment (p = 0.04). Lower leg growth rate was positively correlated to changes in thickness of cutis and subcutis (p = 0.04; r = 0.31). CONCLUSIONS: Reductions in thickness of cutis and subcutis may account for some of the lower leg growth suppression caused by systemic glucocorticoids.

Anthropometry↗
PubMed2003

Vitamin D supplementation to healthy children does not affect serum osteocalcin or markers of type I collagen turnover.

AIM: New serum markers have recently been introduced in the assessment of bone turnover. Such measures are osteocalcin, the C-terminal propeptide of type I procollagen (PICP), the N-terminal propeptide of type I procollagen (PINP) and the C-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP). This study aimed to determine whether supplementation with vitamin D3 to healthy children during the winter affects bone turnover in healthy children measured by serum osteocalcin, PICP, PINP or ICTP. METHODS: 12 girls and 8 boys aged 6.2-13.7 (mean 9.8) y, all proven healthy by medical examination and history, were enrolled in a double-blind, randomized, placebo-controlled, cross-over study with two 4 wk treatment periods and 2 wk washout. Vitamin D3 600 IU was given in one tablet of ABCDin daily. On the last day of the 4 wk periods blood was sampled for assessment of serum osteocalcin, PICP, PINP, ICTP, 25-OH-vitamin D, 1,25-diOH-vitamin D and parathyroid hormone (PTH). RESULTS: During supplementation and placebo periods serum osteocalcin (mean +/- SEM) was 53.9 +/- 5.7 and 54.4 +/- 3.8 microg l(-1) (p = 0.70), PICP was 437+/- 44 and 429 +/- 41 microg l(-1) (p = 0.73), PINP was 579 +/- 56 and 619 +/- 64 microg l(-1) (p = 0.33) and ICTP was 13.4 +/- 0.9 and 13.6 +/- 0.7 microg l(-1) (p = 0.52), respectively. Mean +/- SEM serum 25-OH-vitamin D was 47.0 +/- 2.3 and 33.0 +/- 3.0 nmol l(-1) during vitamin D3 supplementation and placebo (p < 0.001, t = 8.10, 95% CI = 10.3 to 17.6 nmol l(-1)), 1,25-diOH-vitamin D and PTH were 87.5 +/- 4.3 and 92.0 +/- 5.3 pmol l(-1) (p = 0.38), and 3.97 +/- 0.5 and 4.21 +/- 0.4 micromol l(-1) (p = 0.37), respectively. CONCLUSION: Supplementation with 600 IU vitamin D3 to healthy children in the winter does not affect bone turnover as measured by serum osteocalcin, PICP, PINP or ICTP. Vitamin D supplementation to healthy children may not be recommended on the ground of concern for bone turnover.

Child↗
PubMed2002

Short-term treatment with prednisolone has no lasting effect on serum leptin.

It has been suggested that the leptin-stimulating effect of short-term treatment with systemic glucocorticoids may last several weeks to months. The aim of the present study was to assess serum leptin during and four days after withdrawal of short-term treatment with prednisolone. The study comprised 20 healthy subjects (12 men and 8 premenopausal women aged 19-45 years: mean 31 years). The design was a randomized, double-blind, placebo-controlled, parallel group study with 2 days' run in, 3 days' treatment and 4 days' run out. No medication was given during run in and run out. During the treatment period the subjects took prednisolone, 20 mg twice daily, or placebo. Blood was collected on the last day of each period. In the prednisolone group comparisons of run in (mean serum leptin (+/- SEM) (4.94 (1.31)) with treatment (7.08 (1.39)) and run out (5.20 (1.84)) microg/L) showed a significant stimulating effect of treatment (p=0.03, t=-2.6, 95%, confidence interval -4.0 to -0.25 microg/L), whereas no statistically significant variation between run in and run out was detected (p=0.47, t=0.8, confidence interval -2.63 to 1.35 microg/L). Inter-group comparisons of run in with treatment and run out showed elevated leptin concentrations during prednisolone treatment (p=0.03) but no statistically significant variations between run in and run out data (p=0.88). In healthy adults the stimulating effects on serum leptin of short-term prednisolone seem to last only a few days after withdrawal of treatment.

Adult↗
PubMed2002

17-Hydroxylase/17,20 lyase deficiency diagnosed during childhood.

We present a case of familial 17alpha-hydroxylase/17,20 lyase (CYP17) deficiency in which the index case, a 14-year-old XX girl, led to the diagnosis of the condition in a 9-year-old XY sister. No mutations in the CYP 17 gene were found in any of the girls.

Adolescent↗
PubMed2001

Inhaled corticosteroids and growth.

Since inhaled corticosteroids may circulate systemically, a risk of growth suppression in asthmatic children treated with these drugs cannot be ruled out. When assessing the risk, specific drugs, delivery systems, doses, administration regimens, and compliance with treatment regimens must be considered. Although reassuring results have been reported, methodological flaws have meant that the published follow-up evaluations of final height may not be valid for the sound assessment of any growth effects of inhaled corticosteroids. Short-term studies suggest that twice-daily administration of budesonide 200-400 microg delivered from a metered-dose inhaler with a spacer, dry powder budesonide 200 microg, and fluticasone propionate 200 microg per day in children with mild asthma, are not associated with growth-rate effects. The risk may become significant with budesonide 800 microg administered via a metered-dose inhaler with a spacer, and with 400 microg from a dry powder inhaler. The risk of growth suppression can be reduced by dosing once daily in the morning. In children with severe asthma, high doses of inhaled corticosteroids may be potentially lifesaving and thus outweigh the potential risk of mild growth suppression.

Administration, Inhalation↗
PubMed2000

Systemic activity versus systemic adverse effects of nasal glucocorticoids in the treatment of allergic rhinitis.

Treatment with nasal glucocorticoids may be associated with systemic activity, which can be detected by sensitive measures of basal adrenal cortisol secretion, bone turnover and short-term growth (knemometry). The detection of systemic activity, however, does not imply that nasal glucocorticoids cause serious adverse systemic effects, such as an inability of the adrenals to react to physiological stress. Studies assessing the ability of the adrenal cortex to react to stimulation have found this to be intact. Long-term assessments of bone density and statural height are needed, and the possibility of additive effects of intranasal glucocorticoids in children receiving concomitant treatment with inhaled glucocorticoids has not yet been studied. Children on long-term treatment with intranasal glucocorticoids should be followed with height measurements every 6 mo.

Administration, Inhalation↗
PubMed2000

A randomised controlled trial of short term growth and collagen turnover in asthmatics treated with inhaled formoterol and budesonide.

AIMS: To determine effects on short term growth and collagen turnover of adding formoterol (Eformoterol) to half the glucocorticoid dose in children with asthma, treated with inhaled budesonide (Pulmicort Turbuhaler). DESIGN: A randomised double blind, placebo controlled crossover study with two six-week periods. SETTING: Outpatient clinic in secondary referral centre. SUBJECTS: A total of 27 prepubertal children aged 6-13 years. INTERVENTIONS: Formoterol 12 microg and dry powder budesonide 100 microg twice daily in one period; placebo and dry powder budesonide 200 microg twice daily in the other. OUTCOME MEASURES: Primary outcome measures were lower leg growth rate, and serum and urine markers of type I and type III collagen turnover. Secondary outcome measures were inflammation markers in serum, and parameters of asthma control. RESULTS: During budesonide 200 microg twice daily treatment, mean lower leg growth rate was 0.14 mm/week (p = 0.02) lower than during the formoterol and budesonide period. Similar statistically significant effects on markers of collagen turnover were found, whereas inflammation markers and asthma control did not vary statistically significantly between the two periods. CONCLUSIONS: In children treated with inhaled glucocorticoids, halving the dose and adding formoterol is associated with faster short term growth and an increase in markers of collagen turnover, with no loss of asthma control.

Adolescent↗
PubMed1999

Serum leptin in children with asthma treated with inhaled budesonide.

Leptin, a 167-amino-acid peptide, is a recently discovered hormone which is believed to play a major role in the regulation of body weight. Systemic administration of exogenous glucocorticoids has been found to increase circulating leptin levels. In this study, we aimed to assess serum leptin in children with asthma treated with inhaled budesonide 800 micrograms day-1. Ten boys and three girls with asthma, all adolescents aged from 12.9 to 16.6 years, were studied in a randomized double-blind two-period cross-over trial with 4-week treatment periods and a 1-week wash out. Placebo was given during one period and 800 micrograms budesonide during the other via a 750 ml volume spacer (Nebuhaler, Astra Draco, Lund, Sweden). On the last day of the placebo and budesonide periods blood samples were taken and serum leptin was measured by a specific radioimmunoassay. The difference in mean (SEM) leptin concentration between the budesonide and placebo period was 0.2 (0.4) microgram l-1 (P = 0.71; t = -0.4; df = 12, 95% confidence interval -0.9-0.7 microgram l-1). Inhaled budesonide 800 micrograms per day from a Nebuhaler does not influence circulating leptin levels, suggesting that regulation of body weight is unaffected.

Administration, Topical↗
PubMed1999

Androgen secreting adrenocortical tumours.

BACKGROUND: Androgen secreting adrenocortical tumours are rare in children and the determination of their malignant potential can be difficult. OBJECTIVES: To assess the presentation, histology, and clinical behaviour of these tumours. SETTING: Two tertiary referral centres. STUDY DESIGN: Retrospective analysis of children diagnosed with an androgen secreting adrenocortical tumour between 1976 and 1996. PATIENTS: Twenty three girls and seven boys aged 0-14 years. RESULTS: Pubic hair was observed in all children, clitoromegaly or growth of the phallus in 23 children, acceleration of linear growth in 22 children, and advanced bone age (> 1.5 years) in 18 children. Hypersecretion of androgens was detected by assessment of serum androgen concentrations alone in four patients and by 24 hour urine steroid excretion profiles in 22 patients. All 16 tumours measuring < 5 cm in diameter were benign. Of the tumours measuring 5-9 cm, three were malignant and seven were benign, whereas all four tumours > 10 cm were malignant. Histological slides were available for reassessment in 25 children. Although mitoses and necrosis were more characteristic of tumours with malignant behaviour, no exclusive histological features of malignancy were seen. CONCLUSION: Histological criteria for malignancy are not reliable, whereas tumour size is important in assessing malignant potential.

Adolescent↗