Molecular genetics and transfusion management in a child with Bernard Soulier syndrome.

We present a case of Bernard Soulier syndrome in a 9-year-old boy caused by a novel genetic mutation. This child was shown to be homozygous for a single nucleotide deletion (c.1077delG) in the GP1BA gene not previously reported. Clinically, the boy has become refractory to platelet transfusions with both allo-antibodies and iso-antibodies and a massive transfusion requirement for ongoing haemorrhage. We describe the critical role that the blood product transfusion continues to play in the management of Bernard Soulier syndrome and discuss therapeutic options in these patients.     

Deformation behaviour of bovine cancellous bone.

Repetitive cyclic loading from daily activities is reported to induce fatigue damage and microcracking in bone structures. In terms of osteoporotic structures or in cases of serious damage of skeleton segments and the replacement by metallic implants the degree of damage due to cyclic loading will be even more pronounced. It is generally assumed that fatigue induced cracking and crack propagation essentially act as driving forces for complex physiological phenomena such as remodelling processes of bones and the adaptation to applied loads. In cases where the crack propagation rate exceeds the remodelling velocity, sudden and unexpected fracture of the bone is observed. Especially for implant reinforced structures the deviation in stiffness to the bone material can induce high peak stresses and accelerate crack propagation. Whereas, for cortical bone the mechanical behaviour under cyclic loading is sufficiently described, only rough data are available for trabaecular structures. In this study the deformation behaviour of bovine vertebra trabecular bone specimens is investigated under cyclic compressive loading. A powerlaw relationship was found between the applied load ratio and cycles to failure. A linear decrease of maximum, integral strains at failure with increasing applied load ratio was observed. Optical deformation measurement of the surface strains revealed that low strains (0-1 increasing applied load ratio whereby the higher strains behave directly opposite. This indicates that different failure mechanisms are acting at low cycle and high cycle fatigue, respectively.     

Within-gene interaction between c.135 G/A genotypes and RET proto-oncogene germline mutations in HSCR families.

Hirschsprung disease (HSCR) is considered a model for a complex inheritance disorder. Several genes, including the major HSCR-susceptibility RET proto-oncogene, play an aetiological role in the development of HSCR. Genetic linkage analysis in familial HSCR with both long- and short-segment phenotypes has demonstrated a tight linkage to the RET locus, while the phenotype within a HSCR family is characterised by an incomplete penetrance or a variable extension of the aganglionosis. Therefore, additional genetic alterations of RET are postulated in the aetiology or modification of the HSCR phenotype. In this study, the coding region of all 21 exons of the RET proto-oncogene, including the flanking intronic sequences, were investigated by direct DNA sequencing in a HSCR population. We genotyped the c.135 G/A polymorphism and resolved haplotypes comprising the mutation locus and the c.135 G/A polymorphism. Twenty different mutations were detected in 18 of 76 HSCR patients. In ten families the mutations were inherited from the parents, while only four patients had a positive family history for the disease. Moreover, in all ten families an incomplete penetrance of the HSCR phenotype was observed. We have investigated the effect of the non-mutated wild-type allele as well as the c.135 G/A polymorphism on the phenotype within the HSCR families. Our findings support the notion that both RET alleles are involved in the pathogenesis of a subgroup of HSCR patients in a dose-dependent fashion. Additionally, we have shown a modifying effect of the c.135 G/A polymorphism on the HSCR phenotype within HSCR families.     

Impact of asthma and air pollution on school attendance of primary school children: are they at increased risk of school absenteeism?

AIM: The aim of this study was to determine the impact of asthma and air pollution on school attendance of primary school children 6 to 12 years of age in Qatar. STUDY DESIGN: This was a cross-sectional population-based study. SUBJECTS: The total 31,400 Qatari school children at the primary school (16,130 boys and 15,270 girls) 6 to 12 of age were studied to investigate school absenteeism caused by asthma and wheezing during the academic year October 2003 to July 2004. METHODS: We have used the School Health Registry for obtaining the student information and school absenteeism due to asthma and wheezing. Again we had double confirmation on the data obtained on asthmatic children by using the modified version of the International Study of Asthma and Allergies in Childhood [ISAAC] questionnaire. RESULTS: A total of 3,270 (10.4%) pupils were diagnosed as having asthma and wheezing. Overall 2,516 (8.02%) pupils were absent from the school for at least one day during the year. There was a statistically significant difference between asthmatic and wheezing students in number of days absent from the school (p < 0.0001). Most absenteeism occurred during spring for both boys (45%) and girls (47%), followed by autumn for boys (33%) and girls (36%). The measured pollutants reached a peak during the spring season and then in autumn of the studied academic year. CONCLUSION: Children with known asthma miss more days of school than those who do not have asthma. This study finding shows that air pollution has an impact on asthma, which results in significant school absenteeism.