Biomedical subjects

R Bjarnason

Publications and source records attributed to R Bjarnason.

30 records · Page 2Linked to original sources

PubMed1997

Hormonal status of short children born small for gestational age.

The present study was undertaken to evaluate the hormonal status in a subgroup of prepubertal children born small for gestational age (SGA) who lacked postnatal catch-up growth. In this subgroup, a reduced rate of growth hormone (GH) secretion was found, compared with reference groups of healthy children born appropriate for gestational age, of either normal or short stature at the time of investigation. In addition, an abnormal pattern of GH secretion was observed in short children born SGA, which was most pronounced in the younger children, and involved an increased frequency of GH peaks of low amplitude, combined with increased baseline secretion. Levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 were also reduced in short children born SGA, compared with the reference groups. These findings may explain, in part, the lack of postnatal catch-up growth in short children born SGA.

Adolescent↗

PubMed1997

Measurement of human growth hormone receptor messenger ribonucleic acid by a quantitative polymerase chain reaction-based assay: demonstration of reduced expression after elective surgery.

Studies of GH receptor (GHR) gene expression in human tissues have been hampered by the limited amount of tissue available for analysis and the low sensitivity of conventional methods. We have developed a quantitative reverse transcriptase-PCR assay for measurement of GHR messenger ribonucleic acid levels in small human tissue biopsies. To compensate for sample to sample variation, an internal RNA standard, which differs from the wild-type GHR transcript by only a few nucleotides, was reverse transcribed and amplified together with the GHR transcripts. PCR was carried out using one biotinylated primer to permit the purification of single stranded PCR products on streptavidin-coated microtiter plates. The ratio between the wild-type and mutated transcripts was determined by two separate minisequence reactions in which a primer, annealed immediately 3' of a variable nucleotide, was extended by a single 3H-labeled nucleotide, complementary to either the wild-type or mutated sequence. The assay range was 0.125-8 x 10(5) transcripts/sample, the mean intraassay coefficient of variation was 8.7%, and the lower limit of detection was 0.125 x 10(5) transcripts/sample. GHR messenger ribonucleic acid levels were detectable in small amounts (10-100 ng) of total RNA extracted from adipose tissue, skeletal muscle, and liver. The GHR gene expression in liver was approximately 10-fold higher than that in skeletal muscle, whereas intermediate levels were found in adipose tissue. In nine patients undergoing elective abdominal surgery, GHR gene expression in skeletal muscle was reduced on day 3 after surgery compared to the baseline level. The decrease in GHR gene expression was accompanied by a decrease in skeletal muscle glutamine. This suggests that the postoperative protein catabolism may be caused at least partly by acquired GH insensitivity due to reduced expression of the GHR gene.

Abdomen↗

PubMed1997

Growth hormone (GH)-binding protein in prepubertal short children born small for gestational age: effects of growth hormone treatment. Swedish Study Group for Growth Hormone Treatment.

This study was undertaken to characterize the serum levels of GH-binding protein (GHBP) before and during GH treatment in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters. Sixty-seven prepubertal short children (49 boys and 18 girls; height SD score, -5.4 to -2.0; age, 2.0-12.8 yr) born SGA, 8 of whom (6 boys and 2 girls) had signs of Silver-Russell syndrome, participated in the study. Total GHBP was measured by a ligand-mediated immunofunctional assay. The mean (SD) change in height SD score during the year before the start of GH treatment (0.1 IU/kg.day) was 0.11 (0.20) SD score, and this value increased to a 0.84 (0.43) SD score during the first year (P < 0.001) and to a 1.27 (0.63) SD score during the 2-yr period of therapy (P < 0.001). The baseline GHBP values ranged from 49-392 pmol/L, and no relationships were found among sex, chronological age, and maximal GH response to an arginine-insulin tolerance test. A positive correlation between GHBP and body composition, expressed as weight for height SD score, was found in the whole group (r = 0.28; P < 0.05) and in boys (r = 0.44; P < 0.01). No relationship was found between GHBP and spontaneous 24-h GH secretion, in terms of either GH secretion rate or pulsatile pattern, whereas GHBP was positively correlated with insulin-like growth factor I (IGF-I) SD score (r = 0.28; P < 0.05) and IGF-binding protein-3 SD score (r = 0.39; P < 0.01). Using a multiple stepwise linear regression analysis, the model using the IGF-binding protein-3 SD score and the weight for height SD score at the start of GH therapy accounted for 33% of the variance in the baseline GHBP values. A mean increase of 27 (51)% in GHBP levels was found after 1 yr of therapy. However, a high degree of variability in the response of individuals to GH treatment in terms of GHBP levels was observed: in some children GHBP levels increased, whereas in others they decreased. In conclusion, GHBP levels in short prepubertal children born SGA were mostly within the normal range previously reported and correlated directly with body composition. An increase in GHBP levels was observed during GH treatment in some SGA children. No correlation was found between pretreatment GHBP levels and growth response to GH treatment.

Body Composition↗

PubMed1997

Leptin levels are strongly correlated with those of GH-binding protein in prepubertal children.

OBJECTIVE: Nutritional status is an important determinant of growth, and previous studies have indicated that this is due, at least in part, to an increased target-tissue sensitivity to GH. An attractive candidate for mediating this effect is leptin, a hormone secreted by the adipose tissue. The aim of this study was to investigate if there was a connection between GH-binding protein (GHBP) and leptin. DESIGN AND METHODS: We investigated the relationship between serum levels of leptin and those of GHBP in 229 prepubertal children. These included 107 healthy children with normal GH secretion, 55 GH-deficient (GHD) children and 55 children born small for gestational age (SGA) sampled on one occasion for GHBP and leptin, and 12 healthy children followed longitudinally at monthly interval for 1 year. RESULTS: In the healthy children and in those born SGA, the serum concentration of GHBP was positively correlated with that of leptin (r = 0.65, P < 0.001; r = 0.74, P < 0.001 respectively). There was no correlation between GHBP and leptin in the group of children with GHD (r = 0.27, not significant). This means that leptin alone explained 42% of the variation of GHBP in the healthy group and 55% in the SGA group. The correlation remained after adjustment for body mass index and age in the healthy children (r = 0.57, P < 0.0001, r2 = 0.33) and for children born SGA (r = 0.74, P < 0.0001, r2 = 0.55). There was a positive correlation between the intra-individual monthly changes in GHBP and changes in leptin respectively, in the 12 healthy children followed longitudinally, the mean of the correlation coefficients was 0.38 (median = 0.29; range 0.03 to 0.86; P < 0.05). CONCLUSIONS: There was a highly significant correlation between serum levels of leptin and those of GHBP, except in children with GHD. The possibility that leptin could mediate the effects of body fat mass on GH sensitivity, therefore, merits further investigation.

Adolescent↗

PubMed1997

Serum leptin in short children born small for gestational age: relationship with the growth response to growth hormone treatment. The Swedish Study Group for Growth Hormone Treatment.

The product of the obese (ob) gene, leptin, is an adipocyte-derived hormone that is involved in the regulation of appetite and body weight. This study was undertaken in order to describe the basal serum levels of leptin in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters, before and during growth hormone (GH) treatment. Eighty-nine prepubertal short children (66 boys, 23 girls; height standard deviation score (SDS), -5.4 to -2.0; age, 2.0 to 12.8 years) born SGA, 12 of whom (9 boys, 3 girls) had signs of Silver-Russell syndrome, were included in the study. Serum leptin concentrations were measured by radioimmunoassay. Leptin levels in the children born SGA were compared with those in a reference group of 109 prepubertal healthy children born at an appropriate size for gestational age (AGA). The mean (S.D.) change in height SDS was 0.11 (0.22) during the year before the start of GH therapy (0.1 IU/kg/day) and increased to 0.82 (0.44) during the first year (P < 0.001) and to 1.28 (0.59) during the 2-year period of GH therapy (P < 0.001). The children born SGA were significantly leaner than the reference group. An inverse correlation was found between leptin and chronological age in the SGA group (r = -0.31, P < 0.01). The mean serum level of leptin in the children born SGA who were older than 5.5 years of age was 2.8 micrograms/l which was significantly lower than the mean value of 3.7 micrograms/l found in the children born AGA of the same age range. The difference remained after adjustment of leptin levels for sex, age, body mass index (BMI) and weight-for-height SDS (WHSDSSDS). Leptin correlated with WHSDSSDS (r = 0.32, P < 0.001) and BMI (r = 0.36, P < 0.01) in the reference population, but not in the SGA group. No correlation was found between leptin and spontaneous 24-h GH secretion, insulin-like growth factor (IGF)-I or IGF-binding protein-3 levels, or with fasting insulin or cortisol levels. Leptin levels at the start of GH treatment were correlated with the growth response over both 1 year (r = 0.46, P < 0.001) and 2 years (r = 0.51, P < 0.001) of GH therapy. Using multiple regression analysis, models including leptin levels at the start of GH therapy could explain 51% of the variance in the growth response after 1 year and 44% after 2 years of GH treatment. In conclusion, serum leptin levels are reduced in short children born SGA and are inversely correlated with chronological age. Leptin concentrations correlate with the growth response to GH treatment and might be used as a marker for predicting the growth response to GH treatment.

Aging↗

PubMed1996

Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults: I. Effects on insulin-like growth factor-I (IGF-I), GH and IGF binding proteins, and glucose homeostasis.

Recombinant human growth hormone (GH) is routinely administered as daily subcutaneous injections to patients with GH deficiency (GHD). However, in the hypophysectomized rat, pulsatile and continuous infusion of GH has been shown to differ in terms of the magnitude of effect on longitudinal bone growth, serum insulin-like growth factor-I (IGF-I) concentrations, and hepatic metabolism. The aim of the present study was to compare the effects of daily injections and continuous infusion of GH in GHD adults on previously well-documented GH-dependent factors. Recombinant human GH (0.25 U/kg/wk) was administered to nine men with GHD for 14 days in two different ways, ie, as a daily subcutaneous injection at 8 PM and as a continuous subcutaneous infusion, with 1 month of washout between treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatment (day 0) and on day 2 and day 14 of treatment. An oral glucose tolerance test (OGTT) was performed on day 0 and day 14. Daily injections and continuous infusion of GH exerted similar effects in terms of body weight and body composition. The two modes of administration resulted in similar daily urinary GH excretion and similar serum GH concentrations in the morning. GH binding protein (GHBP) concentrations did not change significantly during the various treatment periods. Serum IGF-I and IGF-I binding protein (IGFBP)-3 concentrations increased to a greater degree during continuous infusion of GH versus daily injections. Serum IGFBP-I concentrations decreased to a similar degree during the two modes of administration. Serum concentrations of free triiodothyronine and total triiodothyronine (T3) increased and free thyroxine (T4) decreased to a similar degree, independent of the mode of administration. However, total T4 concentrations were unchanged during both modes of treatment. Serum thyrotropin (TSH) concentrations decreased during continuous infusion, and there was a similar nonsignificant decrease during daily injections of GH. Fasting free fatty acid (FFA) levels increased during treatment with only daily injection of GH, but there was no significant effect from continuous infusion. Results of measurements of fasting concentrations of blood glucose and oral glucose tolerance (OGT) indicated a more impaired glucose tolerance after daily injections of GH versus continuous infusion. In conclusion, continuous infusion and daily injections of GH have similar effects on the variables described, but the magnitude of the effects differs.

Adult↗

PubMed1996

Boy with a ring 7 chromosome: a case report with special reference to dermatological findings.

A ring chromosome 7 was found in an 8-year-old boy investigated on account of short stature and facial dysmorphism. He had a fair skin, almost white hair, cafe-au lait spots and many black atypical pigmented naevi. Electron microscopy of his skin revealed structural changes in melanocytes and keratinocytes, suggesting disturbed cell growth and differentiation.

Cafe-au-Lait Spots↗

PubMed1996

The individual responsiveness to growth hormone (GH) treatment in GH-deficient adults is dependent on the level of GH-binding protein, body mass index, age, and gender.

The aim of the present trial was to study the individual responsiveness to GH treatment in terms of body composition and to search for possible predictors of the response in GH-deficient adults. Sixty-eight patients (44 men and 24 women) with a mean age of 44.3 (1.2) yr and verified GH deficiency participated in a 2-phase treatment trial with an initial randomized, double blind, placebo-controlled, 6-month period, followed by an open treatment period, thereby ensuring all patients 12 months of GH treatment. Recombinant human GH was administered sc daily at bedtime, with a target dose of 12 micrograms/kg x day. GHBP was measured by ligand-mediated immunofunctional assay, and serum insulin-like growth factor I (IGF-I) was determined by RIA after acid-ethanol extraction, using a truncated IGF-I analog as the radioligand. Lean body mass (LBM) and body fat (BF) were determined by dual energy x-ray absorptiometry, and total body water (TBW) was determined by bioelectrical impedance. During the placebo control period, serum IGF-I,LBM, and TBW increased (P < 0.001), whereas BF decreased (P < 0.001) and serum GHBP was unchanged in the group treated with GH compared with the patients treated with placebo. After 12 months of GH treatment, the individual changes in BF ranged from -12.5 to 4.3 kg and from -4.5 to 10.1 kg in LBM. Age (P < 0.05) and baseline GHBP level (P < 0.01) were inversely correlated with the increase in LBM. The GH-induced increment in IGF-I and TBW was greater in men than in women (P < 0.01), whereas the decreases in BF were similar in men and women. This trial demonstrates the variability in responsiveness to GH administration in GH-deficient adults. The best response to GH was obtained in younger patients with low GHBP levels. Furthermore, men responded better than women.

Absorptiometry, Photon↗

PubMed1995

Acute and chronic effects of subcutaneous growth hormone (GH) injections on plasma levels of GH binding protein in short children.

A ligand-mediated immunofunctional assay was used to measure levels of GH binding protein (GHBP) in plasma from children on GH treatment. Blood was drawn at the time of sc injection of GH and thereafter every 2 h for 16 or 24 h in the acute group. The samples were analyzed for GHBP and GH. To study changes in GHBP levels after onset of GH treatment, samples were taken at the start and after 10, 30, and 90 days of treatment (short-term group) and at the start and after 1 and 2 yr of treatment (long-term group). All children in the short-term and long-term groups were prepubertal throughout the study. For the study of short-term and long-term effects of GH treatment, the children were divided into two groups according to the maximal GH response (GHmax) in an arginine-insulin tolerance test and, if available, the maximum peak on 24-h secretion. Children with a GHmax below 20 mU/L(10 micrograms/L) were classified as GH deficient (GHD), and children with a GHmax above 20 mU/L were classified as children of short stature (SS). In the acute group, GH was injected either at 1800 h (n = 73) or at 1000 h (n = 12). In the group given GH at 1800 h there was a decrease in GHBP levels, with the lowest values occurring after 8-10 h, i.e. between 0200 and 0400 h. We have previously reported that there was no correlation between endogenous GH peaks and changes in GHBP levels, but there was a small but significant diurnal variation in GHBP levels (coefficient of variation of about 10%), with a nadir between 0000 and 0400 h. In the group given GH at 1000 h, GHBP levels decreased to a minimum at 10 h after injection (at 2000 h, P < 0.01), with a further decrease at 16 h after injection (P < 0.05), corresponding to the nadir seen in normal children. The mean GHBP levels fell to 71.2% of the baseline value after 90 days in children with GHD (P = 0.004), but was unchanged in children with SS (P = 0.92). In children with GHD, the GHBP levels were unchanged at 1 yr (100.5% +/- 10.7) and 2 yr (97.1% +/- 6.6) after start of treatment. In children with SS, there was no significant increase after 1 yr (125.6% +/- 10.9, P = 0.16) and 2 yr (120.3% +/- 6.4, P = 0.17).(ABSTRACT TRUNCATED AT 400 WORDS)

Body Height↗

PubMed1995

Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls.

OBJECTIVE: To study the occurrence of bronchial obstructive symptoms and immunoglobulin (Ig) E antibodies after respiratory syncytial virus (RSV) bronchiolitis in infancy. Previous studies of this subject have mostly been retrospective or without controls, or the controls have not been followed prospectively. DESIGN: This was a prospective cohort study with matched controls. PARTICIPANTS: Forty-seven infants had experienced RSV bronchiolitis severe enough to cause hospitalization at a mean age of 3 1/2 months. For each child with RSV infection, two controls were acquired from the local Child Health Center and matched for date of birth, sex, and residence. Only one control was obtained for one RSV child, and the control group thus contained 93 children. METHODS: All the children underwent two follow-up examinations, the first one at a mean age of 1 year and the second at a mean age of 3 years. At the first follow-up, a skin-prick test against egg white was performed, and serum IgG antibodies against RSV were measured. At the second follow-up, serum IgE antibodies were measured using screening tests for common food and inhalant antibodies, and skin-prick tests against egg white, cat, birch, and mite allergen were performed. Hereditary and environmental factors (passive smoking, indoor furred animals) and duration of breast-feeding were recorded. RESULTS: At the first follow-up, 89% in the RSV group and 27% in the control group had IgG antibodies against RSV (P < .001). At the second follow-up, asthma, defined as three episodes of bronchial obstruction verified by a physician, was found in 11 of 47 children (23%) in the RSV group and in 1 of 93 children (1%) in the control group (P < .001). A positive test for IgE antibodies was noted in 14 of 44 (32%) RSV children and in 8 of 92 (9%) children in the control group (P = .002). An analysis of risk factors for the development of asthma and IgE antibodies on the whole group of 140 children showed that RSV bronchiolitis was the most important risk factor, and a family history of atopy or asthma further increased the risk. CONCLUSIONS: Respiratory syncytial virus bronchiolitis during the first year of life apparently is an important risk factor for the development of asthma and sensitization to common allergens during the subsequent 2 years, particularly in children with hereditary for atopy/asthma.

Asthma↗

PubMed1994

Eosinophil cationic protein in nasal secretion and in serum and myeloperoxidase in serum in respiratory syncytial virus bronchiolitis: relation to asthma and atopy.

Eosinophil cationic protein (ECP) in nasal secretions was determined in 34 infants with respiratory syncytial virus (RSV) bronchiolitis during the acute infection stage and one and six months later. ECP in serum was determined in 19 of these children at the same time. Myeloperoxidase (MPO) was determined in the same 19 children at the acute infection stage and after one month. All children were followed prospectively for two years after the infection with regard to the development of bronchial obstructive symptoms. Asthma, defined as three or more episodes of bronchial obstruction verified by a physician, developed in 18% of children and less severe obstructive symptoms in 29%. A screening test for food IgE antibodies in serum was performed six months and a skin prick test two years after the acute infection. Nasal ECP/albumin ratios after six months were significantly higher than during the acute RSV infection. MPO, but not ECP, levels in serum were significantly elevated at the time of acute infection compared with levels after one month. Nasal ECP/albumin ratios at the acute infection were compared to a control group of 27 infants with non-RSV upper respiratory tract infections and did not differ. It was not possible to predict, either from ECP/albumin ratios in nasal secretion or from ECP and MPO in serum, which children would develop asthma, other bronchial obstructive symptoms or positive IgE tests.

Acute Disease↗

PubMed1991

Transplantation of cultured autologous epithelium after meningococcal septicaemia in a 4-year-old with 35% skin loss.

A 4-year-old girl with scattered full-thickness skin and soft tissue wounds mainly on the extremities and corresponding to roughly 35% of the total body surface area was treated with early excision and transplantation of cultured autologous epidermal grafts. The transplantation was accomplished in one stage, three weeks after admission. The epidermal cells were cultured in Stockholm, Sweden and the time of transportation of the grafts to Reykjavik, Iceland (seven hours) did not seem to affect the quality, as 85% had taken one week after transplantation. The patient healed completely without further transplantation, but a few local skin flaps were needed to cover exposed articular surfaces. The patient was discharged from hospital with stable grafts five weeks after transplantation.

Cells, Cultured↗