A randomized, placebo-controlled trial of prednisone in early Henoch Schönlein Purpura [ISRCTN85109383]

BACKGROUND: Henoch Schönlein Purpura (HSP) is the most common systemic vasculitis of childhood. There is considerable controversy over whether children with HSP should be treated with corticosteroids. The goal of this study was to investigate whether early corticosteroid administration could reduce the rate of renal or gastrointestinal complications in children with HSP. METHODS: Forty children with HSP, seen in the emergency room of a tertiary-care, paediatric centre, entered a randomized, double-blind, placebo controlled study. The treatment group (n = 21) received oral prednisone, 2 mg/kg/day for one week, with weaning over a second week, while the placebo group (n = 19) received an identical appearing placebo. Co-primary outcomes were the rate of renal involvement at one year and the rate of acute gastrointestinal complications. Co-primary outcomes were analysed using Fisher's Exact test. RESULTS: At one year, there was no difference in the rate of renal involvement (3/21 prednisone group vs. 2/19 placebo group, P = 1.0). There was also no statistically significant difference in the rate of acute gastrointestinal complications (2/21 prednisone group vs. 3/19 placebo group, P = 0.7). Two children in the placebo group did experience intussusceptions compared with none in the prednisone group (P = 0.2). CONCLUSIONS: Early prednisone therapy in HSP does not appear to reduce the risk of renal involvement at one year, or the risk of acute gastrointestinal complications. There may be a reduced risk of intussusception. The routine, early use of prednisone in uncomplicated HSP cannot be recommended at this time

Review of Matrix Metalloproteinases’ Effect on the Hybrid Dentin Bond Layer Stability and Chlorhexidine Clinical Use to Prevent Bond Failure

This review describes the relationship between dentin collagen hybrid bond layer degradation and the Matrix Metalloproteinases (MMPs) after their release by acid etch and rinse adhesives and self etching bonding adhesives that can reduce the bond stability over time. MMP-2, MMP-8 and MMP-9 are indicated as the active proteases that breakdown the collagen fibrils in the hybrid bond layer. Phosphoric acid in the acid etch and rinse bonding process and acid primers in the self etch process are implicated in the release of these proteases and their activation by several non-collagen proteins also released from dentin by the etching. MMPs are released in saliva by salivary glands, by cells in the gingival crevices to crevicular fluid and by pulpal odontoblasts cells to the dentinal fluids. These sources may affect the hybrid layer also. Evidence of the bond strength deterioration over time and the ability of Chlorhexidine to prevent bond deterioration by inhibiting MMP action are discussed. Dentin Bonding procedure utilizing Chlorhexidine for different application times and concentrations are being developed. The application of 2% Chlorhexidine to the phosphoric acid etch surface after rinsing off the acid is the only procedure that has been clinically tested for a longer period of time and shown to prevent bond strength degradation so far. The adoption of this procedure is recommended as means of improving bond stability at this time

Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations

Background: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. Methods: The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. Results: Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. Conclusions: The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations

A YAC contig in Xp21 containing the adrenal hypoplasia congenita and glycerol kinase deficiency genes

The gene loci for adrenal hypoplasia congenita (AHC) and glycerol kinase deficiency (GK) map in Xp21 distal to Duchenne muscular dystrophy (DMD), and proximal to DXS28 (C7), by analysis of patient deletions. We have constructed a yeast artificial chromosome (YAC) contig encompassing a 1.2 Mb region extending distally from DMD, and containing DXS708 (JC-1), the distal junction clone of a patient with GK and DMD. A pulsed-field gel electrophoresis map of the YAC contig identified 3 potential CpG islands. Whole YAC hybridization identified cosmids both for construction of cosmid contigs, and isolation of single copy probes. Thirteen new single copy probes and DXS28 and DXS708 were hybridized on a panel of patients; the deletion mapping indicates that the YAC contig contains both GK and at least part of AHC, and together with the physical map defines a GK critical region of 50-250 kb. In one AHC patient with a cytogenetically detectable deletion we used the new probes to characterize a complex double deletion. Non-overlapping deletions observed in other unrelated AHC patients indicate that the AHC gene is large, extending over at least 200-500 kb. This mapping provides the basis for the identification of the AHC and GK gene

EFFECTS OF LH-RH ON SERUM GONADOTROPINS IN CHILDREN AND ADOLESCENTS

International audienc

Insufficiency of penis development (micropenis). Etiological data in a series of 25 cases.

The diagnosis of micropenis was made in 25 boys aged 1 month to 16 years. This abnormality was associated with hypothalamic-pituitary deficiency in 12 boys (hypogonadotrophic hypogonadism, hypopituitary growth failure, Prader-Willi syndrome), with testicular disorders in 5 boys (anorchia, testicular dysgenesis). In the other 8 the micropenis was an isolated finding but the testicular response to HCG and the LH response to LHRH was significantly reduced (p less than 0.005). The results suggest there may be isolated gonadotrophia deficiency. The variety of conditions that are responsible for micropenis suggest that testosterone deficiency is an important causative factor. HGH may also be important as the penis may be small in HGH deficiency and growth occurs with treatment