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Biomedical subjects

K Albertsson-Wikland

Publications and source records attributed to K Albertsson-Wikland.

At least 109 records · Page 6Linked to original sources
PubMed1994

Circulating growth hormone isoforms in girls with Turner's syndrome.

To evaluate the presence of different GH isoforms in serum of girls with Turner's syndrome, we measured the serum GH content using RIAs with three different site-specific monoclonal antibodies (MAbs). We compared the results to those obtained with authentic GH and GH isoforms. Compared to pituitary GH (mol wt, 22K daltons) as the standard for all three MAbs, serum from girls with Turner's syndrome did not displace tracer [125I]GH equally with all three MAbs. The relative amounts of GH-immunoreactive material found in Turner's syndrome were different from the amounts observed in normal adults and most children with idiopathic short stature. The presence of GH, other than 22K GH, in serum from girls with Turner's syndrome was confirmed by affinity chromatography. The existence of different isoforms of GH, as shown by different cross-reactivity patterns with different MAbs to GH, may explain the conflicting results reported for GH secretion in girls with Turner's syndrome.

Adolescent↗
PubMed1994

Effect of growth hormone treatment on insulin secretion and glucose metabolism in prepubertal boys with short stature.

The purpose of this study was to evaluate the effect on insulin secretion and glucose metabolism of daily growth hormone (GH) treatment, 0.1 U/kg, for up to 3 years in 42 short prepubertal boys without GH deficiency. Their median height standard deviation (SD) score increased from -2.7 to -1.7, whereas their weight for height SD score was unchanged after 3 years of treatment. Fasting plasma glucose concentrations were unchanged, but median fasting insulin concentrations increased from 6.0 mU/l before treatment to 7.8 mU/l (p < 0.05) after the first year. No further increase was seen during the second or third years. The median insulin area under the curve 10-60 min after an intravenous glucose tolerance test increased from 480 mU.l-1.min-1 before treatment to 799 mU.l-1.min-1 (p < 0.05) after 1 year. The median glucose disposal rate (K value) before GH treatment, 2.2%/min, was unchanged after 1 year of treatment. A significant positive correlation was found between the change in the height SD score and the change in fasting insulin concentration during the first (r = 0.45; p < 0.01) and second (r = 0.56; p < 0.05) years of GH treatment. It was concluded that GH treatment in prepubertal children without GH deficiency caused a moderate increase in fasting and stimulated insulin concentrations during the first year of treatment. There was no further change during the following years of treatment, and there were no negative effects on fasting plasma glucose concentrations or glucose disposal rates. The increase in insulin concentration was related positively to the growth response.

Blood Glucose↗
PubMed1994

Assay systems for the growth hormone-binding protein.

The first method used for detection of growth hormone-binding protein (GHBP) in biological fluids was based on the incubation of the sample with radiolabeled GH followed by separation of bound and free GH by gel exclusion chromatography. Recently, other methods have been developed which are faster and easier to use. These methods include variants of the original binding/column assay (e.g., separation of bound and free GH is obtained by immunoprecipitation, charcoal adsorption, ion exchange chromatography, or HPLC), and a ligand-mediated immunofunctional assay (LIFA), in which a monoclonal antibody is used to capture the GHBP on a microtiter plate; all binding sites are saturated with GH and an anti-GH antibody is used to detect the amount of GH (endogenous and exogenous) bound to the GHBP. To permit comparison of results obtained by different methods we have cross-validated the LIFA with two different binding assays: (i) the original long column assay (column assay), and (ii) an assay based on immunoprecipitation (RIPA) of the GH/GHBP complex with an anti-GHBP antibody.

Adolescent↗
PubMed1993

Silver-like syndrome and a small deletion on chromosome 13.

A female child is described with features of Silver's syndrome, including pre- and postnatal growth delay, triangular face, hypertelorism, clinodactyly and developmental delay. In all lymphocytes analyzed, a small deletion was found in chromosome 13. The karyotype was 46,XX,del(13)(q22-32).

Chromosome Aberrations↗
PubMed1993

Longitudinal follow-up of growth in children born small for gestational age.

Postnatal growth was followed in a population-based group of 123 small-for-gestational-age (SGA, birth weight < -2 SD) children (66 boys and 57 girls) to four years of age in order to determine the incidence and time of catch-up growth. Gestational age was determined by ultrasound in gestational weeks 16-17 in all pregnancies, thus eliminating the problem of distinguishing between SGA and preterm infants. Infants with well-defined causes for slow growth rate, i.e. those infants with chromosomal disorders, severe malformations, intrauterine viral infections or cerebral palsy, were excluded. The boys showed an extremely fast weight catch-up, 85% of them reaching weights greater than -2 SD at the age of three months and remaining above this level to the end of the study period. Such a fast catch-up growth was observed in only two-thirds of the girls, but at four years of age 85% of the girls were also above -2 SD. Length catch-up was more gradual than weight catch-up. Of the boys, 54% had lengths below -2 SD at birth, 26% at 1 year of age, 22% at 2 years of age, 17% at 2.5 years of age and 11% (n = 8) at 4 years of age. Corresponding figures for girls were: 69% at birth, 28% at 1 year, 15% at 2 years, 12% at 2.5 years and 5% (n = 3) at 4 years. At 4 years of age, only six boys and three girls remained below -2 SD for both weight and height.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1993

Demography, auxology and response to recombinant human growth hormone treatment in girls with Turner's syndrome in the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study.

Demographic and auxological data were analysed from 818 girls with Turner's syndrome treated with recombinant human growth hormone (GH) and entered into the Kabi Pharmacia International Growth Study. Size at birth was low and correlated with the heights of both parents. The median age at start of GH treatment was 11.4 years and the parents had a median height SDS of -2.9. Height SDS at the start of treatment correlated with parental heights. Height velocities conformed to Turner-specific standards. The weight-for-height index increased sharply above 9 years of age. The frequency of spontaneous appearance of Tanner breast stage 2 was high (34.1% of girls > 10 years of age). Bone age (Greulich and Pyle) data were described by the equation: bone age = 1.61(chronological age) - 0.04(chronological age)2 - 3.61. This equation was used to correct adult height predictions. The median initial dose of GH was 0.8 IU/kg/week and was maintained during the first 3 years of treatment. The median frequency of injections was six/week. Height velocity increased from 4.1 to 6.8 cm/year in the first year, and height velocity SDS for chronological age remained positive for 4 years. The height prediction corrected for bone age increased over the first 2 years only. Differences in demography and auxology were described according to karyotype and country of origin. A greater height velocity SDS was observed at higher GH doses and when oxandrolone was used concomitantly.

Age Determination by Skeleton↗
PubMed1993

Characteristics of children with idiopathic short stature in the Kabi Pharmacia International Growth Study, and their response to growth hormone treatment. International Board of the Kabi Pharmacia International Growth Study.

The auxological characteristics and the response to growth hormone (GH) treatment of children with idiopathic short stature were studied, using the database of the Kabi Pharmacia International Growth Study. Pretreatment data from a total of 271 children were analysed. The children were selected for a birth weight above -2 SDS. The correlation coefficient of birth weight SDS and birth length SDS was 0.51, compared with 0.72 for the reference population. Median length at birth was -0.6 SDS, which fell to -2.5 SDS by 3 years of age. Thereafter, there was no further loss in height SDS. The response to GH treatment was studied in 222 of these prepubertal children who were given six or seven injections/week over a 3-year period. During this time, the median height SDS increased from -2.5 to -1.5, with those children receiving more than 0.65 IU/kg/week having a greater gain in height SDS than those on 0.5 IU/kg/week or less. The degree of bone age delay did not appear to influence the response to GH therapy.

Adolescent↗
PubMed1993

Distinctions between short- and long-term human growth studies.

It is known what the aim is in a complete long-term growth study; the final height is the outcome measure, although the annual height velocity values provide additional information. Strictly, short-term growth studies are also defined in terms of minimum length of observation, i.e. one month, as well as the type of measurement errors to be considered. The poor correlation between short- and long-term growth velocity values has led to the conclusion that the short-term study cannot be interpreted in long-term perspectives, and vice versa. There is a need to debate the way in which results of short-term studies should be interpreted. This is especially important when short-term growth is taken as the outcome measure in a controlled study. Our proposal is that such studies must include information about the growth achieved for a period after the treatment has ended in order to describe possible compensatory growth. Without weighing in some long-term consequences, we may incorrectly document short-term growth as a positive or negative effect of a certain treatment.

Body Height↗
PubMed1993

Intranasal administration of human growth hormone (hGH) in combination with a membrane permeation enhancer in patients with GH deficiency: a pharmacokinetic study.

Recombinant human GH (hGH) combined with a permeation enhancer for the nasal mucosa, sodium tauro-24,25-dihydrofusidate (STDHF), was administered intranasally (in) in six patients with classical GH deficiency. Three different doses were tested (0.2, 0.4, and 0.8 IU/kg BW). The concentration of STDHF was 1% in all doses. As a comparison, all patients received a sc injection of hGH (0.1 IU/kg BW). Blood samples were obtained at frequent intervals for up to 8 h (in doses) or 24 h (sc dose) and analyzed for the plasma concentration of hGH. All three i.n. doses gave a rapid increase in hGH with peak maxima (Cmax) at 20-30 min, and a decline to baseline within 2-3 h. In contrast, the sc dose resulted in a Cmax 2-3 h after the injection, followed by a plateau phase for 2-3 h. The baseline was reached 12-14 h after administration. The uptake [area under the curve (AUC)] was considerably lower for all three in doses, i.e. 1.6-3% of the AUC obtained with the sc dose. However, the Cmax varied between 5.7 +/- 1.4% (0.8 IU/kg BW) and 15.8 +/- 2.1% (0.4 IU/kg BW) of the maximal peak with the sc dose. Of the in doses, 0.4 IU/kg BW resulted in the highest AUC and Cmax. A self-rating protocol was also used to estimate nasal sensations for up to 2 h after dosing. All sensations (itching, burning, sneezing, and running of the nose) were transient and tolerable. This study demonstrates that hGH can be administered intranasally in combination with STDHF. The in dosing results in a plasma peak of hGH very similar to the physiological endogenous peak. No side-effects were noted, other than a transient nasal irritation. Therefore, the nasal route for hGH administration offers a more physiological and more convenient alternative to injections for the treatment of GH deficiency.

Administration, Intranasal↗
PubMed1993

Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion.

The relationship between 24-h GH secretion, insulin-like growth factor (IGF) I serum levels, IGF-binding protein 3 (IGFBP-3) levels and height was studied in 114 healthy children and adolescents (147 tests). A significant correlation was found between the spontaneous GH secretion expressed as the area under the curve above baseline (AUCb) or the calculated 24-h GH secretion rate (GHb) and IGF-I (n = 147, r = 0.65, or 0.78, respectively, P < 0.001) or IGFBP-3 levels (r = 0.48 or 0.62, P < 0.001). Correlations were also significant within the various subgroups [females (n = 51), males (n = 96), prepubertal children (n = 75), pubertal children (n = 72)]. The slopes of the regression lines of IGF-I levels vs. AUCb or GHb were clearly steeper in pubertal children than in prepubertal ones; this was not as evident with IGFBP-3. In prepubertal children, a significant correlation was found between height (compared to Swedish reference values) standard deviation scores (SDS) and IGF-I SDS (n = 75, r = 0.66, P < 0.001) or IGFBP-3 SDS (r = 0.61, P < 0.001). The reproducibility during repeated testing (19 individuals, 6 prepubertal) was best with IGFBP-3 as compared to AUCb, GHb, or IGF-I which showed considerable variability. The data suggest: 1) that IGF-I and IGFBP-3 serum levels reflect spontaneous GH secretion in healthy individuals; 2) IGF-I levels are more sensitive to GH regulation than IGFBP-3; 3) in puberty, there may be increased sensitivity of IGF-I regulation by GH as compared to the prepubertal stage; 4) short children have low IGF-I and IGFBP-3 levels, whereas tall children have high levels, a fact which is likely to contribute to the understanding of height variability in a healthy population; 5) the good reproducibility of IGFBP-3 on repeated testing makes it an interesting parameter for the evaluation of the GH-IGF-axis. IGFBP-3 measurements may substitute for GH profiles in many cases, when the goal is an estimation of the GH secretion rate.

Adolescent↗
PubMed1993

Analysis of 24-hour plasma profiles of growth hormone (GH)-binding protein, GH/GH-binding protein-complex, and GH in healthy children.

Human blood contains a high affinity GH binding protein (GHBP) which corresponds to the extracellular domain of he GH-receptor. It has been suggested that GHBP can modify the biological actions of GH, and alter the distribution of GH in the body. To study the hormonal regulation of growth, it is therefore necessary to measure GHBP as well as GH. We recently developed a ligand-mediated immunofunctional assay (LIFA) which allows separate quantitation of total GHBP (free and GH-bound) and the complex formed by GH and GHBP (GH/GHBP-complex) in human blood. We have now used the ligand-mediated immunofunctional assay to measure GHBP levels in plasma profiles from healthy children. GH was measured by immunoradiometric assay. Fifteen 24-h plasma profiles from 12 healthy children (3 girls and 9 boys) of different ages (6-15 yr), heights (-2.5 to +3.0 SD scores) and pubertal stages (1-4) were examined. Blood was withdrawn continuously for 24 h and collected in 20-min fractions. Time series for GH, GHBP, and GH/GHBP-complex were analyzed by cross-correlation and Fourier analysis. GH was secreted in a pulsatile fashion in all subjects. The concentration of the GH/GHBP-complex varied during the sampling period, and the changes correlated significantly with the GH pulses with correlation coefficients reaching maximum at zero time lag. In contrast, the changes in the total GHBP concentration were minor (coefficients of variation approximately 10%), and not correlated to GH pulses. Fourier analysis showed similar spectral power patterns for GH and GH/GHBP-complex, suggesting a diurnal rhythm (12- to 24-h periods) as well as components of higher frequencies (around 4-h periods). Although there were only subtle fluctuations in the total GHBP concentration, Fourier transformation revealed a diurnal rhythm with nadir during the night, while components of higher frequencies were much less abundant. We conclude that variations in total GHBP as measured by LIFA during a 24-h sampling period are small and that the concentration can be estimated from a single random blood sample.

Adolescent↗
PubMed1993

Time-resolved immunofluorometric assay of human growth hormone.

We describe a time-resolved immunofluorometric assay (trIFMA) for human growth hormone (hGH), in which monoclonal antibody (mAb)-coated microtiter strip wells and a europium (Eu) chelate-labeled mAb are used. We compare the new trIFMA, in which two mAbs are used, with an immunoradiometric assay (IRMA) in which polyclonal antibodies are used. Serum samples (n = 185) from 36 children with various diagnoses were analyzed. In addition, 24-h profile samples (72 per child) from 39 children were analyzed. The trIFMA was more sensitive (detection limit, 0.03 mIU/L) than existing IRMAs. Both the intra- and interassay CVs were < or = 10.6% for hGH concentrations between 1 and 100 mIU/L. The trIFMA is technically simple and rapid, requires no centrifugation or separation reagent, and has a counting time of only 1 s per sample. In addition, the Eu label is nontoxic, presents no waste-disposal problems, and has a long shelf-life. Finally, the assay requires only small volumes of serum (25 muL), which is of considerable importance in pediatric use. The mAbs used for the trIFMA selectively bind the 22-kDa form of hGH, with the result that the assay detects about 80% of the amount detected by the polyclonal IRMA.

Antibodies, Monoclonal↗
PubMed1992

Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure. The International Board of the Kabi Pharmacia International Growth Study.

To assess the role of growth hormone in fetal and infant growth, we analyzed the pretreatment data on 52 patients with a diagnosis of congenital growth hormone deficiency before 2 years of age, obtained from the Kabi Pharmacia International Growth Study. These infants had reduced birth-length standard deviation scores, an excess of birth weight relative to length, and progressive growth failure. We conclude that congenital growth hormone deficiency may cause impaired growth in utero and early infancy, and that growth hormone plays an important role in perinatal and infantile growth.

Analysis of Variance↗
PubMed1992

Developmental changes in 24-hour profiles of luteinizing hormone and follicle-stimulating hormone from prepuberty to midstages of puberty in boys.

To establish the pubertal changes in gonadotropin secretion, 24-h secretory profiles of LH and FSH were studied in 10 healthy boys by ultrasensitive (sensitivity, 0.019 and 0.014 IU/L, respectively) time-resolved immunofluorometric assays 21 times. Five of the 10 boys were sampled on 2-6 occasions over a time interval of 0.95-6.4 yr. When sampled, 6 boys were prepubertal (testicular volume, less than 3 mL), 8 boys were early pubertal (testicular volume, 3-5 mL), and 7 boys were midpubertal (testicular volume, 10-25 mL). Plasma was taken every 20 min for 24 h. All boys had LH and FSH pulses. In prepuberty, the mean LH level was much lower than the mean FSH level, and neither showed significant diurnal variation. In early puberty, the mean LH level increased much more than that of FSH. For LH, the increase in mean levels was due to an increase in both pulse amplitude and frequency. During early and midpuberty, these changes were most marked at night, leading to the appearance of diurnal variation. For FSH, the mean levels increased progressively from prepuberty to midpuberty, with a slight increase in the mean pulse amplitude at the onset of puberty, whereas no change in pulse frequency was found. In contrast to LH, no diurnal variation was found for FSH at any of the pubertal stages. Thus, at the onset of puberty, gonadotropin secretion undergoes specific changes, which are different for LH and FSH, involving changes in pulse amplitudes and frequencies and development of diurnal variation for LH.

Adolescent↗
PubMed1992

Reproducibility of 24-h growth hormone profiles in children.

The rate of GH secretion and the pattern of GH peaks were compared in a group of nine prepubertal children during their prepubertal period in repeated 24-h GH profiles. At investigation, the children were 6-13 years old (at first profile 6-11 years old) and of normal height (+/- 2 SD). Two profiles were obtained per child, (with a mean time interval of 1.5 years, range 0.7 to 3.5 years. The calculated GH secretions of the first and second profiles were compared. As a group, no significant differences in secreted amount of GH, when expressed as data from the second profile as a percentage of data from the first profile (93 +/- 8%), number of peaks (98 +/- 7%) or mean peak amplitudes (92 +/- 11%), were obtained. Between the repeated curves of an individual child, maximal difference in secretion, number of peaks and mean peak amplitudes ranged around +/- 30%, with a mean intraindividual cv of 12%. The reproducibility in the peak distribution for all profiles was also analysed. The relative frequencies is a percentage of the GH peak amplitudes and peak widths were virtually identical in the repeated profiles. Reproducibility of the temporal pattern of profiles was analysed using time-series analysis (Fourier analysis) and showed no difference in rhythmicity between the different occasions. In conclusion, a high reproducibility of both GH secretion and GH pattern was found for the whole group of prepubertal children.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1991

A longitudinal study of growth and growth hormone secretion in children during treatment for acute lymphoblastic leukemia.

Diminished growth rate during treatment for acute lymphoblastic leukemia (ALL) is of the multifactorial etiology. Effects on GH secretion have been shown after discontinuation of treatment including prophylactic CNS irradiation. Seventeen children treated for ALL with three different CNS preventive schedules were followed longitudinally with repeated estimations of the spontaneous GH secretion during a 24-month period. No difference was found in GH secretion during this time between patients who had received no radiotherapy and those who had received 18 or 24 Gy as CNS prophylaxis. During dexamethasone treatment the GH secretion was completely suppressed, which can be a mediator for the diminished growth rate during the first 2 years of ALL treatment. We conclude that there is no clinical reason to perform GH analysis within the first 24 months of treatment for ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Growth in infancy and childhood in girls with Turner's syndrome.

We describe spontaneous longitudinal growth in girls with Turner's syndrome (TS), using the infancy-childhood-puberty (ICP) growth model. Length/height during the first 12 years of life was studied in 58 Swedish girls with TS. Their mean length at birth was 47.8 cm (SDS -1.4) and mean height at 12.0 years of age 127.3 cm (SDS -3.0). A clear age-dependent subnormality was observed in the change in length-height SDS (delta SDS). Mean delta SDS values at ages 0.0 to 0.5 and 3.0 to 6.0 years were normal. In contrast, the mean delta SDS at ages 0.5 to 3.0 and 6.0 to 12.0 years were subnormal. The onset of the childhood growth component (normally located between 0.5 and 1.0 year of age) was, on the average, delayed by 0.28 year. This accounts for the subnormality of delta SDS at 0.5 to 3.0 years of age. About 50% of the variation in height at 12.0 years of age, as determined by a multiple linear regression analysis, was significantly explained by length at 0.5 year of age, age at the onset of the childhood component, and delta SDS at 6.0 to 12.0 years of age.

Adolescent↗