Tissue Factor Pathway Inhibitor Gene Polymorphism -33T → C Predicts Improved Disease-Free Survival in Colorectal Cancer.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is an anticoagulant with antimetastatic properties. The homozygous CC polymorphism of TFPI (-33T â†’ C) is associated with higher TFPI levels and lower venous thromboembolism risk. This study was the first to evaluate the impact of this polymorphism on disease-free survival (DFS) in cancer patients after curative resection. METHODS: A prospectively maintained tumor bank with clinical data was used to identify patients who underwent curative surgery for colorectal cancer between 1994 and 2006. Germline DNA was extracted from formalin-fixed, paraffin-embedded normal colonic mucosa. Single nucleotide polymorphisms for TFPI (-33T â†’ C), factor V Leiden (G1691A), and prothrombin (G20210A) were determined by polymerase chain reaction. Survival analysis was described using the Kaplan-Meier method. Multivariable regression analysis was performed using the Cox proportional hazard model. RESULTS: Of the 127 patients identified, the CC genotype was found in 11 %. Venous thromboembolism incidence was 18 % in the TT/TC (wild type/heterozygous) genotypes and 7 % in the CC genotype (p = 0.46). The CC genotype was associated with superior DFS (hazard ratio 0.34, 95 % confidence interval 0.14-0.84; p = 0.02) with 5-year DFS of 63 vs. 24 % for CC vs. TT/TC, respectively. In multivariate analysis, CC polymorphism (hazard ratio 0.28, p = 0.008) was independently associated with improved DFS. The prevalence of factor V Leiden (0.8 %) and prothrombin (1.6 %) polymorphisms was too low to detect interaction with TFPI polymorphism or DFS. CONCLUSIONS: These findings indicate that the inherited anticoagulant homozygous -33T â†’ C TFPI polymorphism may protect against colon cancer recurrence and suggests a mediating role for the coagulation system in cancer outcomes.

Ly49 cluster sequence analysis in a mouse model of diabetes: an expanded repertoire of activating receptors in the NOD genome.

The mouse Ly49 and human killer cell immunoglobulin-like receptors (KIR) gene clusters encode activating and inhibitory class I MHC receptors on natural killer (NK) cells. A direct correlation between the presence of multiple activating KIR and various human autoimmune diseases including diabetes has been shown. Previous studies have implicated NK cell receptors in the development of diabetes in the non-obese diabetic (NOD) inbred mouse strain. To assess the contribution of Ly49 to NOD disease acceleration the Ly49 gene cluster of these mice was sequenced. Remarkably, the NOD Ly49 haplotype encodes the largest haplotype and the most functional activating Ly49 of any known mouse strain. These activating Ly49 include three Ly49p-related and two Ly49h-related genes. The NOD cluster contains large regions highly homologous to both C57BL/6 and 129 haplotypes, suggesting unequal crossing over as a mechanism of Ly49 haplotype evolution. Interestingly, the 129-like region has duplicated in the NOD genome. Thus, the NOD Ly49 cluster is a unique mix of elements seen in previously characterized Ly49 haplotypes resulting in a disproportionately large number of functional activating Ly49 genes. Finally, the functionality of activating Ly49 in NOD mice was confirmed in cytotoxicity assays.

Calcifying aponeurotic fibroma features seen on fine-needle aspiration biopsy: case report and brief review of the literature.

Calcifying aponeurotic fibroma is a rare benign soft tissue proliferation, which occurs in the distal extremities in children. We describe a case of calcifying aponeurotic fibroma of the hand in a 9 year-old male diagnosed by FNA. Clinically and radiographically this mass was felt to be suspicious for sarcoma, likely alveolar rhabdomyosarcoma. Cytologic examination revealed benign appearing spindled cells, chondroid cells, multinucleated giant cells and calcific debris. These features recapitulate the classic histologic features of calcifying aponeurotic fibroma. Conservative excision was performed and histologic exam confirmed the diagnosis. To the authors' knowledge, this is the first description of the cytologic features of this entity.

Stability of aqueous solutions of amoxicillin sodium in the frozen and liquid states.

The stability of aqueous admixtures of amoxicillin sodium in both the liquid and frozen (solid) states was studied. Admixtures of amoxicillin sodium were prepared in sterile water for injection to a theoretical concentration of 10 mg/mL. For each experimental run, 2-mL aliquots of the admixture were placed in stoppered glass volumetric flasks and stored at temperatures ranging from 19.5 degrees C to -30 degrees C; 16 flasks were stored at each temperature. After equilibration for approximately 20 minutes, duplicate flasks at each temperature were removed from storage conditions for time-zero assay. Subsequently, duplicate flasks were assayed at various times, depending on the storage temperature, for up to 13 days or until more than 80% of the drug had degraded. All samples were assayed at least in duplicate using high-performance liquid chromatography. When amoxicillin solutions were in the liquid state (at temperatures between 19.5 and 0 degrees C), the time required for the amoxicillin concentration to decrease to 90% of its initial value (t90) increased as temperature decreased. However, between 0 degree C and -7 degrees C, the t90 of frozen solutions decreased from two days to 1.08 hours. As temperature declined further, the rate of degradation decreased until the solution was completely frozen; at -30 degrees C, the t90 had increased to 13 days. Amoxicillin sodium is unstable in aqueous solutions stored between 0 degrees C and -20 degrees C. If admixtures of this drug are to be frozen for later use, the storage temperature should be below -30 degrees C.