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Biomedical subjects

C Heuck

Publications and source records attributed to C Heuck.

11 recordsLinked to original sources

Adverse effects of inhaled budesonide (800 micrograms) on growth and collagen turnover in children with asthma: a double-blind comparison of once-daily versus twice-daily administration.

BACKGROUND: Twice-daily administration of inhaled budesonide (400 micrograms) suppresses short-term growth in children with asthma. OBJECTIVE: To compare short-term growth and markers of collagen turnover during treatment with 800 micrograms of inhaled budesonide administered once daily in the morning and 400 micrograms administered twice daily. PATIENTS: Twenty-four children with asthma aged 5.6 to 12.5 years. SETTING: An outpatient secondary referral center. METHODS: A randomized, double-blind, crossover trial with 2 treatment periods of 4 weeks was conducted, and growth was assessed with a knemometer. The carboxy terminal propeptide of type I procollagen, the amino terminal propeptide of type I procollagen (PINP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen, the amino terminal propeptide of type III procollagen (PIIINP), and urinary pyridinoline and deoxypyridinoline were evaluated. RESULTS: Mean lower leg growth rate (P = .04), PINP (P = .03), and PIIINP (P < .01) were suppressed during twice-daily administration of budesonide, 400 micrograms. Otherwise, no statistically significant differences were detected. CONCLUSIONS: As compared with 400 micrograms of inhaled budesonide administered twice daily, 800 micrograms administered once daily in the morning has a sparing effect on short-term growth and collagen turnover.

Administration, Inhalation

Diurnal rhythm of serum osteocalcin in normal children.

The aim of the present study was to assess diurnal levels of serum osteocalcin in normal children using a recently introduced fluoroimmunoassay (Pharmacia Osteocalcin CAP FEIA) measuring solely the intact peptide. Five girls and two boys aged 10.4-13.6 (mean 12.2) y were studied. Blood samples for determination of osteocalcin were collected every 2h throughout the day. A statistically significant rise in serum osteocalcin (F = 6.7, p < 0.001) with a peak at 08.00 h and a nadir lasting from 10.00 to 24.00 h was found. Trough and peak levels (at 16.00 and 08.00 h, respectively) were 41.6 +/- 6.8 and 66.0 +/- 10.5 microg l(-1) (mean +/- SEM). The circadian variation should be taken into consideration when single assessments of serum osteocalcin in children are performed.

Adolescent

Differential effects of inhaled budesonide on serum osteocalcin in children and adolescents with asthma.

In recent years, measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogenous glucocorticoids. Studies in children with asthma on inhaled glucocorticoids, however, have shown inconsistent results. The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide using three different osteocalcin assays: the Pharmacia Osteocalcin CAP FEIA, the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays. Two studies were conducted: 1) a randomised double blind two-period crossover study of 22 prepubertal children aged 5-12 years. In one period 800 microg budesonide was given once in the morning, in the other 400 microg was given twice daily; 2) a randomised double blind placebo controlled two period crossover study of inhaled budesonide 400 microg twice daily in fourteen 13-16 year old adolescents with pubertal stages II-V. In both studies, treatment periods were of four weeks duration, and blood samples were collected at the last day of each period. In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods. In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment. The suppression reached statistical significance with the CAP FEIA (P = 0.03) and the OSTK-PR (P = 0.01) assays, but not with the ELSA-OSTEO assay (P = 0.06). Correlation analyses showed statistically significant correlation coefficients varying between 0.58 and 0.91 (P = 0.03 and P < 0.0001, respectively). The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied, and inhaled glucocorticoids have differential effects in children and adolescents.

Administration, Inhalation

A placebo-controlled study of three osteocalcin assays for assessment of prednisolone-induced suppression of bone turnover.

Serum osteocalcin is a sensitive marker of suppressive effects of exogenous glucocorticoids on bone turnover. It has been suggested, however, that the degree of suppression detected by different assays may vary. Whether discrepancies between various assays influence conclusions from group studies of exogenous glucocorticoids has not been evaluated. The aim of the present study was to compare the CAP fluoroimmunoassay (FEIA), OSTK-PR and ELSA-OSTEO assays for assessment of prednisolone-induced effects on serum osteocalcin. Twelve men and eight premenopausal women aged 19-45 (mean 31) years were studied. All subjects were healthy. The design was a randomised double-blind, placebo-controlled parallel- group study with 2 days run-in, 3 days treatment and 4 days run-out. During run-in and run-out no medication was given. During the treatment period the subjects took either 20 mg prednisolone twice daily or placebo. Blood was collected on the last day of each period. Intra- and intergroup comparisons showed prednisolone treatment to be associated with a statistically significant suppression of osteocalcin which was detected by all assays (ANOVA;P<0.0001). In the individual subjects the response to prednisolone was the same for each assay. The CAP FEIA, OSTK-PR and ELSA-OSTEO assays seem equally sensitive for evaluation of osteocalcin in group studies of oral glucocorticoids.

Adult

WHO's laboratory programme.

The dependence of modern medicine on laboratory services has increased enormously during the last 50 years. Rapid developments in this field present a challenge for standard setting and quality control.

Chemistry, Clinical

Short-term growth and collagen turnover in asthmatic adolescents treated with the inhaled glucocorticoid budesonide.

Short-term lower leg growth, the insulin-like growth factor axis, and collagen turnover were assessed in 16 adolescents with asthma during treatment with inhaled budesonide, 800 micrograms/d, from a pressurized metered dose inhaler with a volume spacer. The design was a randomized double blind, placebo-controlled two-period crossover trial with treatment periods of 4 weeks and a 1-week wash-out. Lower leg growth was assessed by knemometry. Serum levels of insulin-like growth factor-I, insulin-like growth factor-binding protein-3, and the following markers of collagen turnover were evaluated: Serum markers of type I collagen formation and degradation; the carboxy-terminal propeptide of type I procollagen and the carboxy terminal pyridinoline cross-linked telopeptide of type I procollagen (ICTP), the serum marker of type III collagen formation; the amino-terminal propeptide of type III procollagen (PIIINP) and the urinary concentrations of the type I collagen degradation products pyridinoline (PYD) and deoxypyridinoline (DPD) cross-links. Mean lower leg growth velocity was suppressed from 0.51 mm/week during placebo to 0.18 mm/week during budesonide treatment (p < 0.001). No statistically significant effects on insulin-like growth factor-1, insulin-like growth faster-binding protein-3, or carboxy-terminal propeptide of type I procollagen were observed. ICTP and PIIINP were reduced with 2.3 and 2.5 micrograms/liter (p < 0.001 and p < 0.001, respectively) during budesonide treatment, urinary concentrations of PYD and DPD with 32.9 nmol/mmol creatinine (p < 0.005) and 6.8 nmol/mmol creatinine (p < 0.005), respectively. Significant correlations between lower leg growth velocity and ICTP, PIIINP, PYD, and DPD during placebo (p < 0.01, p < 0.05, p < 0.01, and p < 0.01) and budesonide (p < 0.05, p < 0.05, p < 0.05, and p < 0.05) periods were found. Short term lower leg growth suppression in adolescents treated with inhaled budesonide, 800 micrograms/d, reflects suppression of type I and III collagen turnover.

Administration, Topical

Serum and urinary markers of types I and III collagen turnover during short-term prednisolone treatment in healthy adults.

During recent years new sensitive serum and urinary makers have been introduced for assessment of collagen turnover. The aim of the present study was to assess whether short-term prednisolone treatment is associated with any adverse effects on serum levels of the type I collagen synthesis marker, the carboxy terminal propeptide of type I procollagen (PICP); on the type I collagen degradation marker in serum, the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP); on a serum marker of type III collagen synthesis, the aminoterminal propeptide of type III procollagen (PIIINP), or on the type I collagen degradation markers urinary pyridinoline (PYD) and deoxypyridinoline (DPD) concentrations. We studied 12 men and 8 premenopausal women aged 19-45 years (mean 31). All subjects were healthy. The design was a randomized double-blind, placebo-controlled parallel group study with a 2-day run-in, a 3-day treatment period and a 4-day run-out. During run-in and run-out no medication was given. During the treatment period the subjects took either prednisolone, 40 mg per day, or placebo. Blood and urine were collected at the last day of each period. The intergroup comparisons of run-in treatment values showed that prednisolone suppressed PICP (p < 0.001) and PIIINP (p < 0.001). PICP levels remained suppressed during run-out, whereas PIIINP returned to pretreatment levels. NO prednisolone-induced effects on ICTP or on urinary PYD or DPD were detected by the intergroup comparisons. Short-term prednisolone treatment is associated with suppressive effects on type I and III collagen turnover. Whether serum PICP is more sensitive than urinary PYD and DPD for detection of short-term suppressive effects on type I collagen turnover remains to be further evaluated.

Adult

Insulin-like growth factor axis, bone and collagen turnover in children with atopic dermatitis treated with topical glucocorticosteroids.

BACKGROUND: Topical glucocorticosteroids are widely used in the treatment of children with atopic dermatitis. Due to percutaneous absorption, these agents may become systemically available and cause inhibition of growth in children. However, the mechanisms responsible for the growth-suppressive effective are not fully understood. OBJECTIVE: To evaluate whether treatment with topical budesonide has any adverse effects on growth-hormone-dependent serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), and on the serum markers of bone and collagen turnover osteocalcin, the carboxy-terminal propeptide of type I collagen (PICP), the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and the amino-terminal propeptide of type III procollagen (PIIINP). METHODS: 13 children (mean age 9.5 years) with atopic dermatitis were studied in an open longitudinal trial with run-in and budesonide treatment periods of 2 weeks' duration. During the run-in, only emollient was used. During the treatment period, budesonide cream 0.025% followed by emollient were applied twice daily all over the body except on the face. At day 14 of each period, blood samples were taken and eczema was scored according to a severity index based on extent and activity of the disease. RESULTS: Compared to the run-in, budesonide treatment was associated with a statistically significant reduction in mean severity index (p = 0.002). No statistically significant effects on serum levels of IGF-I, IGFBP-3, osteocalcin or ICTP were observed. The serum concentrations of PICP and PIIINP were reduced with (mean +/- 1 SD) 43 +/- 64 milligrams (95% confidence interval 3.5-80 milligrams, p = 0.03, t = 2.4, d.f. = 12) and 1.2 +/- 1.5 milligrams (95% confidence interval 0.3-2.1 milligrams, p = 0.01, t = 3.0, d.f. = 12), respectively. CONCLUSION: Type I and III collagen turnover may be suppressed during short-term treatment with topical budesonide in children with atopic eczema. clinical implications need further study.

Administration, Topical

Knemometry in children with atopic dermatitis treated with topical glucocorticoids.

Recently the knemometer, a lower leg length measuring device, has been introduced for sensitive assessment of systemic activity of exogeneous glucocorticoids in children. The aim of this study was to assess by means of knemometry whether the topical glucocorticoid budesonide affects short-term growth in children with atopic dermatitis. Fourteen children 5 to 12 years old were studied in an open longitudinal trial with three periods of 2 weeks duration. In periods 1 (run-in) and 3 (run-out), the children were treated with emollient. In period 2, budesonide cream 0.025% was followed by emollient twice daily to all of the body except the face. Eczema was evaluated according to a score based on extent and activity. Knemometry was performed twice weekly. Compared to the run-in and run-out periods the mean growth rate during budesonide treatment was reduced by 0.11 mm/wk (p > .05) and 0.40 mm/wk (p < .05), respectively. The mean growth rate during run-out was increased by 0.29 mm/wk as compared to run-in (p < .05). Compared to run-in the mean severity indices during budesonide treatment and run-out were reduced by 1.55 (p < .05) and 1.55 points (p <.05), respectively. The concomitant variations in lower leg growth rate and disease activity suggest that short-term treatment with topical glucocorticoids may provide a better growth potential during the weeks after withdrawal of the treatment. Whether this is due to improved disease control needs further study. Being a noninvasive method, knemometry may be useful for comparing different topical glucocorticoids and administration regimens in children in whom vasoconstrictor assays are difficult.

Administration, Topical

Calculation of knemometric growth rates in group studies of children treated with exogenous glucocorticoids.

Calculation of growth rates in short-term knemometry studies is often based on linear regression analysis. The method, however, has not been compared to the conventional method for calculation of growth rates (increase in length divided by the time interval) in glucocorticoid-treated populations. The aim of the present study was to assess whether the conventional method for calculation of growth rates is as sensitive as the linear regression method in the assessment of short-term lower leg growth in group studies of children treated with exogenous glucocorticoids. Three different studies were conducted during which knemometry was performed once or twice weekly. Six boys and six girls aged 5-12 years, with atopic dermatitis, participated in an open longitudinal study with three periods of 2 weeks duration. Ten boys and four girls aged 12-16 years, with asthma, were studied in a randomized double-blind, placebo-controlled two-period crossover trial, with treatment periods of 4 weeks. Thirteen boys and 11 girls aged 5-12 years, with asthma, were enrolled in a randomized double-blind two-period crossover trial with treatment periods of 4 weeks. During active treatment periods topical budesonide was given. Mean lower leg growth rates and the results of significance tests based on the two methods for calculation of growth rates were similar in all studies. Significant correlations between the growth rates based on the two methods were found in the non-glucocorticoid and glucocorticoid treatment periods in all studies (Pearson correlation r coefficient varied from 0.81 to 0.97, p from < 0.001 to < 0.0001). The conventional method for calculation of lower leg growth rates is as reliable as linear regression analysis. By using the conventional method the number of visits required for knemometric growth rate assessment in group studies of systemic activity of exogenous glucocorticoids can be reduced.

Administration, Cutaneous