Growth impairment in children with atopic eczema.

Growth was studied in 89 children with atopic eczema aged 1-16 years. Nine (10%) had a standing height below the 3rd centile. Both boys and girls had significantly reduced sitting height but normal subischial leg length, and both sexes had significantly delayed skeletal maturity scores. Impaired growth was particularly associated with widespread eczema, but also with the presence of asthma and the potency of topical corticosteroid. Six of the 15 patients with a corrected height centile below the 10th centile had been receiving potent (British National Formulary category I or II) topical corticosteroids. This study suggests that impaired linear growth is a feature of atopic eczema. While the causes of the growth impairment are unclear, there is a need for caution in the use of potent topical corticosteroids in children.     

Raised somatomedin activity in the serum of young boys with Perthes' disease revealed by bioassay. A disease of growth transition?

This paper reports a study of the serum somatomedin activity in 67 boys with Perthes' disease and in 43 control boys aged three to 11 years. It was undertaken to evaluate some abnormalities of growth in children with Perthes' disease that have been previously reported. A brief account is given of knowledge relating to somatomedins in postnatal and fetal life. Serum somatomedin activity was measured using a bioassay based on the principle that somatomedins stimulate the synthesis of both DNA and proteoglycans in porcine costal cartilage. In control boys, the serum somatomedin activity increased with age, which is consistent with previous reports for normal children. In affected boys, the normal increase in serum somatomedin activity with age did not occur. The somatomedin activity in affected boys is higher than in control boys at three to five years but not at six to 11 years of age. Findings support the hypothesis that some children with Perthes' disease have an abnormality of the growth hormone-dependent somatomedins. The serum findings together with those of both skeletal age delay and impaired skeletal growth distally in the limbs are consistent with the view that the general disorder of some children with Perthes' disease results from an imbalance in mechanisms that determine the postnatal transition from the "fetal" to the "basic" component of the normal human growth curve.     

The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3

The Lutheran blood group glycoprotein, first discovered on erythrocytes, is widely expressed in human tissues. It is a ligand for the alpha5 subunit of Laminin 511/521, an extracellular matrix protein. This interaction may contribute to vaso-occlusive events that are an important cause of morbidity in sickle cell disease. Using x-ray crystallography, small-angle x-ray scattering, and site-directed mutagenesis, we show that the extracellular region of Lutheran forms an extended structure with a distinctive bend between the second and third immunoglobulin-like domains. The linker between domains 2 and 3 appears to be flexible and is a critical determinant in maintaining an overall conformation for Lutheran that is capable of binding to Laminin. Mutagenesis studies indicate that Asp312 of Lutheran and the surrounding cluster of negatively charged residues in this linker region form the Laminin-binding site. Unusually, receptor binding is therefore not a function of the domains expected to be furthermost from the plasma membrane. These studies imply that structural flexibility of Lutheran may be essential for its interaction with Laminin and present a novel opportunity for the development of therapeutics for sickle cell disease.     

Vitamin D Concentrations at Birth and the Risk of Rheumatoid Arthritis in Early Adulthood: A Danish Population-Based Case-Cohort Study

Background: Low vitamin D in pregnancy may impair the development of the fetal immune system and influence the risk of later development of rheumatoid arthritis (RA) in the offspring. The aim was to examine whether lower 25-hydroxyvitamin D3 (25(OH)D) concentrations at birth were associated with the risk of developing RA in early adulthood. Methods: This case-cohort study obtained data from Danish registers and biobanks. Cases included all individuals born during 1981–1996 and recorded in the Danish National Patient Register with a diagnosis of RA with age >18 years at first admission. The random comparison consisted of a subset of Danish children. Vitamin D concentrations were measured in newborn dried blood. In total, 805 RA cases and 2416 individuals from the subcohort were included in the final analysis. Weighted Cox regression was used to calculate hazard ratio (HR). Results: The median (interquartile rage (IQR)) 25(OH)D concentrations among cases were 24.9 nmol/L (IQR:15.4;36.9) and 23.9 nmol/L (IQR:13.6;36.4) among the subcohort. There was no indication of a lower risk of RA among individuals in the highest vitamin D quintile compared with the lowest (HRadj.:1.21 (0.90;1.63)). Conclusion: The risk of RA in early adulthood was not associated with vitamin D concentrations at birth.     

Delayed skeletal maturation in Perthes' disease

We have studied skeletal maturation and carpal bone development in 27 girls with Perthes' disease by assessing consecutive radiographs during an observation time of 5 years. At the time of diagnosis of Perthes' disease, delayed skeletal maturation was both frequent and considerable and greater than at the end of observation. The mean age at appearance of carpal bones was delayed compared with controls. In bilateral disease, compared with unilateral disease, the onset of ossification in the carpals occurred later.