Thermal modulation for gas chromatography

A thermal modulator device for gas chromatography and associated methods. The thermal modulator device includes a recirculating fluid cooling member, an electrically conductive capillary in direct thermal contact with the cooling member, and a power supply electrically coupled to the capillary and operable for controlled resistive heating of the capillary. The capillary can include more than one separate thermally modulated sections

NYESO-1/LAGE-1s and PRAME Are Targets for Antigen Specific T Cells in Chondrosarcoma following Treatment with 5-Aza-2-Deoxycitabine

Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA) family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC) in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression.We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment.A minority (36%) of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic chondrosarcoma patients where no proven systemic therapies exist

Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure: a randomized crossover clinical trial

Patients with non-apposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with "open abdomens" would have bioavailability similar to that of matched patients with closed fascial edges. Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15. Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51% +/- 30% in the open abdomen and 63% +/- 19% (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30%-100% in both groups. Three patients developed rectal colonization with Candida krusei. The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy

The Need for Aggressive Nutritional Intervention in the Injured Patient: The Development of a Predictive Model

Early nutritional intervention has been advocated in trauma patients. We have developed a model to identify those patients who will most benefit from the invasive and costly measures that are required to provide injured patients with early enteral feedings. Four hundred forty-two patients admitted to a level I trauma center during a 2-month period were evaluated using 21 clinical variables. Time to tolerance of a regular diet was used as the dependent variable in a step-wise regression, and then the selected variables were used to build a classification and regression tree to predict tolerance of a regular diet within 5 days. Our findings demonstrate that intensive care unit disposition, Injury Severity Score, Abdominal Trauma Index, and the need for early surgical intervention are important predictors regarding the need for early nutritional intervention. When the model was applied to the study population, it had a sensitivity of 83%, a specificity of 84%, and an accuracy of 84%