SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer

The gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is located at the chromosomal region 18q21. In order to evaluate the clinical relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage using real-time quantitative PCR in 202 colorectal tumour biopsies from a previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4 diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy with a border line significance (overall survival: 3.23, P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with the previous observation that patients whose cancer had retention of the 18q21 region had a significantly higher benefit from 5-fluorouracil-based therapy. Moreover, these results may provide a refinement at the gene level of the clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive marker in colorectal cancer. This data also indicate that integrity of this component of the transforming growth factor-beta/bone morphogenetic protein signalling pathway may be a critical factor for benefit of chemotherapy in patients with colorectal cancer

Relationship between aeroallergen and food allergen sensitization in childhood

Background Previous studies measuring the prevalence of allergen sensitization have been relatively small and used small numbers of allergens. To effectively evaluate children with atopic disease, we need an accurate knowledge of which allergens are important.Objective To measure the prevalence of sensitization within a large unselected birth cohort, to examine the associations between sensitization to different allergens and determine whether atopy can be defined by a small panel of allergens.Methods The Avon Longitudinal Study of Parents and Children is a population-based birth cohort of 13 638 singletons surviving to 4 weeks of age. The cohort was skin tested at 7 years of age to house dust mite (Dermatophagoides pteronyssinus), grass pollens, cat, peanuts, mixed tree nuts and egg and one of three other panels: animal danders, foods or aeroallergens. Sensitization was defined as a weal diameter of 3 mm. The strength of associations between sensitization to different allergens was tested by calculating the odds ratio adjusted for sensitization to D. pteronyssinus and grass pollen and gender.Results Valid data were obtained from 6412 singletons. Sensitization was most common to aeroallergens: grass pollens (8.5%), D. pteronyssinus (7.8%), cat (4.9%), D. farinae (3.6%), dog (2.7%), horse (1.4%), rabbit (1.4%). Of the foods tested, the most common sensitization was to peanut (1.4%) and mixed tree nuts (1.0%). More than 95% of subjects with sensitization to any of the 29 allergens tested were sensitized to one of grass, D. pteronyssinus or cat allergen. There were strong associations of multiple sensitizations both within and between different allergen classes (pollens, animals, foods, peanut and tree nuts).Conclusions Seven-year-old children in the UK are primarily sensitized to aeroallergens, but also to peanuts and tree nuts. There are strong associations between sensitization within allergen groups as well as between allergen groups. Further studies are required to observe whether similar associations are seen with clinical allergy to these allergens

The Fight Against the Slime: Can We Ever Win?

Microorganisms universally attach to surface and produce extracellular matrix of polysaccharidic nature termed slime. This phenomenon is now regularly referred to as biofilm formation. Biofilm-associated infections pose a serious problem for public health because bacteria growing in a biofilm are more recalcitrant to the action of antibiotics and host defenses than cells growing in a planktonic state. In orthopedic surgery, such proprieties of biofilm made prosthesis-associated infection a devastating complication. In such a “war,” the prevention with adequate pharmacological prophylaxis, pathogen-specific treatment, and the combination antimicrobial regimens are of paramount importance. The better knowledge in PJI pathogenesis and biofilm formation, reached in these last years, is a new weapon in the armamentarium of physicians