A surveillance tool to support quality assurance and research in personalized medicine.

Developing effective methods to enable the practice of personalized medicine is a national priority for translational science. By leveraging modern genotyping technology and health information technologies, prescribing therapies based on genotype becomes an achievable goal. Within this manuscript, we describe the development, implementation, and piloting of a surveillance tool to assure the quality of clinical decision making in the context of new pharmacogenetic information. The surveillance tool allows a quality assurance (QA) team to review significant genotyping results and deliver focused educational interventions to providers. We report on the first eight patients undergoing genotyping to support antiplatelet therapy selection after drug-eluting stent placement. The collected pilot data supports an informatics approach to QA process management, as our tool delivered actionable patient information. It also enabled providers to tailor antiplatelet therapy to individual patients' genotypes. Our expectation is to continue collecting surveillance reports to perform an in-depth analysis of our tool.

P53 mutations in carcinoma breast--a clinicopathological study.

OBJECTIVES: To find out the incidence of p53 mutations and their possible correlation with clinicopathological presentation in females with breast carcinoma. SETTINGS: Department of Surgery, Pakistan Institute of Medical Sciences, Islamabad. PATIENTS AND METHODS: Seventy four patients with operable carcinoma breast that underwent mastectomy were included in this prospective study. Tumour tissue specimens and peripheral blood samples were examined for p53 mutations. Age, tumour size, nodal status and histopathology was assessed in patients with and without p53 mutations. RESULTS: Ten (13.5%) patients showed p53 mutations in their tumour specimens while 64 (86.48%) had normally functioning p53 gene. Patients were divided into two groups, A (normally functioning p53), and B (mutated p53). Intraductal carcinoma was the most frequent histological variant(A = 57, B = 10), while lymph nodes were involved in 67.19% (A = 47) and 60% (B = 6) cases respectively. The age of patients and clinical parameters (tumour size, nodal status and histopathological diagnosis) were compared between the two groups and no statistically significant correlation between p53 mutations and clinicopathological parameters was found. CONCLUSIONS: It was concluded that p53 mutation is present in carcinoma breast in Pakistani population but there was no significant correlation between p53 mutation and tumour aggressiveness (size, nodal status and histopathology).

Determination of parameters for enzyme therapy using L-asparaginase entrapped in canine erythrocytes.

The antitumor agent L-asparaginase was entrapped in canine erythrocytes by a single dialysis encapsulation (efficiency mean = 30%). Concentration of asparaginase in carrier cells was about 240 IU/ml, with an average of 62% cell recovery. Use of a double dialysis procedure increased the L-asparaginase concentration within carrier cells to 530 IU/ml, with an overall cell recovery of 53.9%. In vitro efflux experiments showed L-asparaginase-loaded canine carriers were stable at both 4 and 37 degrees C for an 18-h period. In vivo cell survival studies showed that carrier cells did circulate and that L-asparaginase had a half-life of 6.5 days. No evidence suggesting that the enzyme left the cell was found. Carrier cells prepared with [3H]inulin and [14C]sucrose were stored at 4 degrees C for 2 weeks and began to show signs of deterioration after 2 days.

Targeting of mycotoxins to reticuloendothelial system of mice with carrier erythrocytes.

The tricothecene mycotoxin, T-2 toxin, was encapsulated in bovine erythrocytes for in vivo delivery of T-2 toxin to macrophages. Intraperitoneal injection of bovine carrier erythrocytes (5 X 10(8) cells) containing T-2 toxin saturated mouse liver uptake of erythrocytes by 6 h postinjection. At 24 h postinjection, 20% of the injected carrier cells containing toxin were localized in the liver of mice. Saturation of the liver uptake of bovine carrier cells was independent of encapsulated or free T-2 toxin. A dose of T-2 toxin sufficient to inhibit 50% of the macrophage protein synthesis was targeted to the liver via the carrier erythrocytes. A methodology for delivery of highly toxic molecules to liver macrophages is described.

Interaction of T-2 toxin with bovine carrier erythrocytes: effects on cell lysis, permeability, and entrapment.

Hemolysis, morphological changes, binding, and effect on encapsulation of exogenous substances were used as a basis to study the interaction of the trichothecene mycotoxin, T-2 toxin, with erythrocytes. T-2 toxin did not cause hemolysis of bovine erythrocytes but readily hemolyzed rat erythrocytes. T-2 toxin interaction with bovine erythrocytes was minimal because T-2 toxin did not bind appreciably to the erythrocytes. Entrapment of T-2 toxin in carrier erythrocytes was independent of toxin concentration, and interaction of T-2 toxin with erythrocytes did not affect the entrapment of the markers sucrose or inulin. T-2 toxin rapidly diffuses from carrier erythrocytes with less than 20% remaining after 4 hr of incubation. Cross-linking of the erythrocyte membrane with glutaraldehyde prevents T-2 toxin efflux from carrier erythrocytes.