Computational Modeling of Factor Xa Inhibition by Immobilized Tissue Factor Pathway Inhibitor

Coating surfaces of implanted devices with anticoagulants can reduce thrombosis and studies using a recombinant form of endogenous tissue factor pathway inhibitor (rTFPI) are promising. The anticoagulant function of immobilized rTFPI is thought to occur primarily by its inhibition of plasma clotting factor Xa (FXa); however the kinetics of this reaction at a surface are as yet unknown. To better understand the surface inhibition reaction under flow conditions, a theoretical model was developed delineating the roles of mass transport and reaction kinetics for an in vitro parallel plate device used in prior experimental studies [Hall et al., J. Biomech. Eng. 120:484–490, 1998]. As a first approximation, the kinetics of inhibition of FXa by rTFPI reported for static, homogeneous systems was considered. The unsteady convection–diffusion equation was solved for different wall-shear rates and inlet concentrations of FXa using the computational fluid dynamics software CFD-ACE (ESI Software Group). The results show that the heterogeneous inhibition reaction is diffusion controlled prior to saturation of the rTFPI. The experimental results compare favorably with the model at the lower shear rates (100–400 s⁻¹). At higher shear rates (>400 s⁻¹) the theoretical results follow the same trend as the experimental results but show a greater inhibition of FXa, implying an effect of flow or shear on the inhibition reaction.     

Serum copper levels in carcinoma of ovary and cervix

The role of serum copper level (SCL) as a diagnostic and prognostic tool in genital tract malignancies was evaluated. SCL was employed as a marker for response to treatment (surgical/radiotherapy). 129 women attending gynaecology outpatient department or admitted in the gynecology ward were studied. Of these 77 patients in the disease (study) group were proven cases of genital tract malignancies and 52 served as controls. Outcome measures studied were: SCL levels estimated before initiation of any treatment i.e. surgery/radiotherapy; thereafter, at two weeks after completion of treatment. Follow up of the study subjects was done between 4-8 weeks and 8-10 weeks, when the patients were evaluated for any recurrence of disease and SCLs were also estimated. Kruskal-Wallis one-way analysis of variance determined whether values varied significantly among the different groups studied. Mean SCLs were found to be significantly elevated in cases of Ca ovary (n = 15), early CaCx (n = 14) and late CaCx (n = 48), as compared to the control group, comprising of women with no signs and symptoms of malignancy (n = 52). SCLs decreases significantly (P < 0.001) after treatment of Ca ovary and CaCx. These results indicate a possible clinical usefulness of estimating serum copper levels in women with genital tract cancer and suggest a role for SCL in the evaluation of the disease activity and as a prognostic tool in the management of genital malignancies.     

Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients.

PURPOSE: To assess the Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in adult and pediatric oncohematologic patients. PATIENTS AND METHODS: The study was conducted in four patient groups: those with fever of unknown origin (FUO) during neutropenia, suspected pulmonary infection (PI), or nonpulmonary aspergillosis (NPA) and those undergoing surveillance (S) after hematopoietic stem-cell transplantation (HSCT). IA was classified as definite, probable, or possible, according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions. RESULTS: A total of 3,294 serum samples were collected during 797 episodes (FUO, 261; PI, 297; NPA, 28; and surveillance, 211), and 153 episodes of IA were diagnosed (31 definite, 67 probable, and 55 possible). Three episodes were first suspected from galactomannan ELISA; the remaining 150 cases were diagnosed from clinical or radiologic evidence. Sensitivity of the ELISA was 64.5%, 16.4%, and 25.5% in definite, probable, and possible episodes of IA, respectively, and was lower in patients positive for anti-Aspergillus antibodies than in antibody-negative patients. Most false-positive results occurred in children and in allogeneic HSCT (allo-HSCT) patients. Overall specificity of the ELISA was 94.8%. It was lower in children compared with adults (P <.0001) and in allo-HSCT patients compared with non-allo-HSCT adults (P =.0002). Lowering the ELISA cutoff value from 1.500 to 0.700 seemed more relevant for non-allo-HSCT adults (sensitivity, 73.1%, 44.3%, and 44.7% in definite, probable, and possible IA, respectively; specificity, 94%). CONCLUSION: Galactomannan ELISA seems less sensitive than previously described, and sensitivity can be further reduced by the presence of anti-Aspergillus antibodies. A new cutoff value for the ELISA of 0.700 is proposed for non-allo-HSCT adults.