Measuring socio-economic inequalities in the presentation of injuries to a paediatric A&E department: the importance of an epidemiological approach

OBJECTIVES: To contrast the socio-economic pattern of childhood injuries presenting to a paediatric accident and emergency (A&E) department revealed by using both a numerator-based and a denominator-based approach to the analysis of injury surveillance data. METHODS: Injury surveillance data collected during 1997-1998 at a Glasgow children's hospital A&E department were analysed. Socio-economic status was measured using Carstairs' deprivation index. Data from West Glasgow postcode sectors only were analysed in order to optimize epidemiological validity. Socio-economic patterning of injury was investigated in two ways-numerator-based and denominator-based. RESULTS: A total of 12,762 children (0-14 years) living in West Glasgow attended the A&E department of the Royal Hospital for Sick Children over the study period. Both analytical approaches showed a clear and statistically significant excess of injury presentations in children from more deprived postcode sectors, but the variation appeared much greater in the numerator-based rather than the denominator-based approach. In regression analysis, however, only the denominator-derived rates showed a statistically significant linear trend across deprivation categories. CONCLUSION: The most appropriate and accurate means of measuring the extent of socio-economic (and other) inequalities in injury risk is to adopt a population-based rather than numerator-based perspective on the data collected by injury surveillance systems.     

Lattice corneal dystrophy associated with familial systemic amyloidosis (Meretoja's syndrome)

A 79-year-old white man of Irish descent presented with lattice corneal dystrophy, blepharochalasis, and peripheral seventh cranial nerve palsies. Family studies revealed that his 23-year-old daughter had early lattice cornea dystrophy. The corneal button removed by penetrating keratoplasty exhibited characteristic amyloid accumulation by light and electron microscopy. Biopsy of the patient's normal appearing conjunctiva and skin of the lower lid revealed amyloid. Biopsy of the daughter's conjunctiva was negative for amyloid, but her lid skin had characteristic amyloid deposits by light and electron microscopy. Immunoperoxidase strains were negative for AA and AP and serum prealbumin and SAA proteins were normal. Meretoja's syndrome has rarely been described outside a small geographic region in Finland. The clinical and histopathologic findings of this entity are discussed and contrasted to isolated "lattice corneal dystrophy."     

Mapping of a Gene for Alopecia with Mental Retardation Syndrome (APMR3) on Chromosome 18q11.2-q12.2

Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder characterized by total or partial absence of hair from the scalp and other parts of the body and associated with mental retardation. Previously, we have reported the mapping of two alopecia and mental retardation genes ( APMR1 and APMR2 ) on human chromosome 3. In the present study, after excluding both of these loci through linkage analysis, a whole genome scan was performed by genotyping 396 polymorphic microsatellite markers located on 22 autosomes and the X and Y chromosomes. A disease locus was mapped to a 10.9 cM region, flanked by markers D18S866 and D18S811, on chromosome 18q11.2–q12.2. A maximum two-point LOD score of 3.03 at θ= 0.0 was obtained with marker D18S1102. Multipoint linkage analysis resulted in maximum LOD scores of 4.03 with several markers in the candidate region. According to the Rutgers combined linkage-physical map of the human genome (build 36) this region covers 12.17 Mb. DNA sequence analysis of nine candidate genes including DSC3 , DSC1 , DSG1 , DSG4 , DSG3 , ZNF397 , ZNF271 , ZNF24 and ZNF396 did not reveal any sequence variants in the affected individuals of the family presented here.     

A cysteine protease activity from Plasmodium falciparum cleaves human erythrocyte ankyrin

The malaria parasite Plasmodium falciparum undergoes distinct morphologic changes during its 48-h life cycle inside human red blood cells. Parasite proteinases appear to play important roles at all stages of the erythrocytic cycle of human malaria. Proteases involved in erythrocyte rupture and invasion are possibly required to breakdown erythrocyte membrane skeleton. To identify such proteases, soluble cytosolic extract of isolated trophozoites/schizonts was incubated with erythrocyte membrane ghosts or spectrin-actin depleted inside-out vesicles, which were then analyzed by SDS-PAGE. In both cases, a new protein band of 155 kDa was detected. The N-terminal peptide sequencing established that the 155 kDa band represents truncated ankyrin. Immunoblot analysis using defined monoclonal antibodies confirmed that ankyrin was cleaved at the C-terminus. While the enzyme preferentially cleaved ankyrin, degradation of protein 4.1 was also observed at high concentrations of the enzyme. The optimal activity of the purified enzyme, using ankyrin as substrate, was observed at pH 7.0-7.5, and the activity was strongly inhibited by standard inhibitors of cysteine proteinases (cystatin, NEM, leupeptin, E-64 and MDL 28 170), but not by inhibitors of aspartic (pepstatin) or serine (PMSF, DFP) proteinases. Furthermore, we demonstrate that protease digestion of ankyrin substantially reduces its interaction with ankyrin-depleted membrane vesicles. Ektacytometric measurements showed a dramatic increase in the rate of fragmentation of ghosts after treatment with the protease. Although the role of ankyrin cleavage in vivo remains to be determined, based on our findings we postulate that the parasite-derived cysteine protease activity cleaves host ankyrin thus weakening the ankyrin-band 3 binding interactions and destabilizing the erythrocyte membrane skeleton, which, in turn, facilitates parasite release. Further characterization of the enzyme may lead to the development of novel antimalarial drugs.     

Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families

Background  Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. Affected male individuals have normal beard hair.
Objectives  To search for pathogenic mutations in the human P2RY5 gene in Pakistani families with autosomal recessive hereditary hypotrichosis.
Methods  In the present report, 16 unrelated consanguineous Pakistani families having multiple affected individuals with autosomal recessive hypotrichosis were investigated. Linkage in these families was searched by genotyping microsatellite markers linked to autosomal recessive hypotrichosis loci LAH1, LAH2 and LAH3. Thirteen of the families showed linkage to the LAH3 locus on chromosome 13q14.11–q21.32. These families were then subjected to direct sequencing of the P2RY5 gene, which encodes a G protein-coupled receptor.
Results  Sequence analysis of the P2RY5 gene revealed two novel missense mutations (c.742A>T; p.N248Y and c.830C>T; p.L277P) in three families. Five previously described mutations including three missense (c.188A>T; p.D63V, c.436G>A; p.G146R, c.562A>T; p.I188F), one insertion (c.69insCATG; p.24insHfsX52) and one complex deletion (c.172–175delAACT; 177delG; p.N58–L59delinsCfsX88) were detected in the other 10 families.
Conclusions  Mutations revealed in the present study extend the body of evidence implicating the P2RY5 gene in the pathogenesis of human hereditary hair loss.