The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Pulmonary oxidative stress response in young children with cystic fibrosis

BACKGROUND: It has been suggested that oxidative stress contributes to lung injury in cystic fibrosis. There is, however, no direct evidence of increased pulmonary oxidative stress in cystic fibrosis nor of the effects of inflammation on the major pulmonary antioxidant, glutathione. A study was undertaken to measure these parameters in infants and young children in the presence or absence of pulmonary inflammation. METHODS: Thirty two infants and young children with cystic fibrosis of mean (SD) age 21.4 (15.3) months (range 2-54) and seven non-cystic fibrosis control subjects of mean (SD) age 21.0 (21.2) months (range 2-54) were studied using bronchoalveolar lavage (BAL). On the basis of the BAL findings the cystic fibrosis group was divided into those with (CF-I) and those without pulmonary inflammation (CF- NI). Levels of lipid hydroperoxide, total glutathione, and gamma- glutamyl transpeptidase (gamma-GT) were then measured in the BAL fluid. RESULTS: The concentrations of lipid hydroperoxide and gamma-GT in the epithelial lining fluid were significantly increased in the CF-I group compared with the control and CF-NI groups, each of which had similar values for these parameters (ratio of geometric means for CF-I group versus control for lipid hydroperoxide 5.4 (95% confidence interval (CI) 1.8 to 15.8) and for gamma-GT 5.2 (95% CI 1.4 to 19.4)). The glutathione concentration tended to be lower in the CF-I subjects but the difference did not reach statistical significance. CONCLUSIONS: These results demonstrate that the airways in patients with cystic fibrosis are exposed to increased oxidative stress which appears to be a consequence of pulmonary inflammation rather than part of the primary cystic fibrosis defect. The increase in gamma-GT in the CF-I group suggests a mechanism by which extracellular glutathione could be utilised by airway epithelial cells.