Laboratory diagnosis of thrombophilic states: where do we stand?

Until recently the laboratory diagnosis of thrombophilia consisted on investigation of the plasmatic anticoagulant pathways and the search for dysfibrinogenemia and antiphospholipid antibodies/lupus anticoagulants. More recently, the laboratory investigation has been expanded by including activated protein C (APC) resistance, due or not to the presence of the factor V Leiden mutation; hyperprothrombinemia, due to the presence of the prothrombin mutation G20210A and hyperhomocysteinemia, due to impairment of the relevant metabolic pathway because of enzymatic and/or vitamin deficiency. Testing for thrombophilia may be useful for many reasons. First, the results of testing may provide valuable information to assess the risk of recurrence in the proband. Second, testing family members is useful for prophylactic and diagnostic purposes. Third, the identification of patients bearing combined defect helps to identify those at increased risk for thrombosis. Testing is recommended for patients with a past history of thrombosis and should be extended to their first-degree family members. Since most of the tests are not reliable during anticoagulation, it is preferable to postpone laboratory testing until after discontinuation of the treatment. Whenever possible testing should be performed by means of functional assays. DNA analysis is required for the prothrombin mutation G20210A. Laboratory diagnosis for antiphospholipid antibodies/lupus anticoagulant should be performed by a combination of tests including phospholipid-dependent clotting assays and solid phase anticardiolipin antibodies. Hyperhomocysteinemia may be assessed by high-pressure liquid chromatography methods, or by fluorescence polarization immunoassays.     

Comparative in vitro study on a ultra-high roughness and dense titanium coating

A new implant surface has been developed with the purpose of avoiding as much stress shielding as possible, and thus prolong the prosthesis lifespan. The aim of this study was to investigate the in vitro effect of this new ultra-high roughness and dense Titanium (Ti) surface (PG60, Ra = 74 microm) in comparison with medium (TI01, Ra = 18 microm) and high (TI60, Ra = 40 microm) roughness and open porous coatings; all the coatings were obtained by vacuum plasma spraying. MG63 osteoblast-like cells were seeded on the tested materials and polystyrene, as control, for 3 and 7 days. Cells proliferated on the material surfaces similarly to the control. Alkaline phosphatase activity had lower values for TI60 than TI01 (p < 0.0005) and PG60 (p < 0.005). Osteocalcin levels measured on TI60 were significantly (p < 0.0005) lower in comparison with TI01 and PG60 at 7 days. Procollagen-I synthesis reduced with increasing roughness and the lowest data was found for PG60. While at 3 days Transforming Growth Factor beta1 levels augmented with increasing roughness, at 7 days TI60, the high roughness surface, was significantly lower than PG60 (p < 0.005) and TI01 (p < 0.001). All tested materials showed significantly higher Interleukin-6 levels than those of polystyrene at both experimental times. Nitric Oxide activity on TI01 was significantly (p < 0.05) higher than on TI60 and polystyrene. In conclusion, the new ultra-high roughness and dense coating PG60 provided a good biological response, even though, at least in vitro, it behaved similarly to the coatings already used in orthopaedics.     

Comparative Disease Assessment: a multi-causal approach for estimating the burden of mortality

Journal of Public Health - The Comparative Risk Assessment (CRA) framework comprehensively evaluates the impact of exposure to risk factors on health populations using the counterfactual causal...     

Alterations in Breast Cancer Biomarkers Following Neoadjuvant Therapy

Annals of Surgical Oncology - Biomarker changes in patients with residual disease (RD) after neoadjuvant systemic therapy (NAT) have unclear consequences. This study examined the prevalence of...     

Comparison of multiple oncotype DX® from the same patient

For women with breast cancer in whom multiple Oncotype DX^® Recurrence Scores (RS) are obtained, RS concordance utilizing current NCCN recommendations has not been evaluated. Patients with two or more RS were identified. RS were stratified by NCCN guidelines and compared for concordance. Twenty-four patients were evaluated. RS concordance varied by tumor type: 100% in the same tumor, 91.7% in multiple ipsilateral tumors, 71.4% in contralateral tumors, and 66.7% in in-breast recurrent tumors. RS concordance for multiple assays in the same patient is not high enough to omit Oncotype DX^® testing for each tumor.     

Mental health services and the city: a neighbourhood-level epidemiological study

Journal of Public Health - Neighbourhood composition is considered a social determinant of mental health that can be addressed by policymakers to improve outcomes. Deprived neighbourhoods typically...     

Dolichol-bound oligosaccharides and the transfer of distal monosaccharides in the synthesis of glycoproteins by normal and tumor mammary epithelial cells

Summary The main dolichol diphosphate-bound oligosaccharides present in primary cultures of both normal and tumor mouse mammary epithelial cells had the same size, yielded the same pattern after acetolysis and paper chromatography, had the same number of mannose residues susceptible to-mannosidase degradation, and were composed of the same monosaccharide residues. This is the first demonstration that normal and tumor mammary cells have dolichol diphosphate-bound oligosaccharides with very similar, if not identical, structures. These compounds are intermediates in the synthesis of asparagine-linked oligosaccharides. On the other hand, normal and tumor cells showed differences in the specific activities of the enzymes involved in the transfer of the distal monosaccharides from the sugar nucleotides to glycoproteins. Sialyl- and fucosyl-transferases were elevated and galactosyl- and N-acetylglucosaminyltransferases were diminished in mammary tumor cells. The intact tumor cells showed an increased fucosylation of glycoproteins of the asparagine-linkage type. Address for reprints: Roberto L. Ceriani, M.D., Ph.D., Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, 51st and Grove Streets, Oakland, CA 94609, USA.