Patient-derived acute myeloid leukemia (AML) bone marrow cells display distinct intracellular kinase phosphorylation patterns

Multiparametric analyses of phospho-protein activation in patients with acute myeloid leukemia (AML) offers a quantitative measure to monitor the activity of novel intracellular kinase (IK) inhibitors. As recent clinical investigation with FMS-like tyrosine-3 inhibitors demonstrated, targeting IK with selective inhibitors can have a modest clinical benefit. Because multiple IKs are active in patients with AML, multikinase inhibitors may provide the necessary inhibition profile to achieve a more sustained clinical benefit. We here describe a method of assessing the activation of several IKs by flow cytometry. In 40 different samples of patients with AML we observed hyper-activated phospho-proteins at baseline, which is modestly increased by adding stem cell factor to AML cells. Finally, AML cells had a significantly different phospho-protein profile compared with cells of the lymphocyte gate. In conclusion, our method offers a way to determine the activation status of multiple kinases in AML and hence is a reliable assay to evaluate the pharmacodynamic activity of novel multikinase inhibitors

Psychiatric Disorders in Patients Presenting to the Emergency Department for Minor Injury

BACKGROUND: Thirty-five percent of all Emergency Department (ED) visits are for physical injury. OBJECTIVES: To examine the proportion of patients presenting to an ED for physical injury with a history of or current Axis I/II psychiatric disorders and to compare patients with a positive psychiatric history, a negative psychiatric history, and a current psychiatric disorder. METHODS: A total of 275 individuals were selected randomly from adults presenting to the ED with a documented anatomic injury but with normal physiology. Exclusion criteria were: injury in the previous 2 years or from medical illness or domestic violence; or reported treatment for major depression or psychoses. Psychiatric history and current disorders were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual Disorders, 4th edition (DSM-IV), a structured psychiatric interview. Three groups (positive psychiatric history, negative psychiatric history, current psychiatric disorder) were compared using Chi-square and analysis of variance. RESULTS: The sample was composed of men (51.6%) and women (48.4%), with 57.1% Black and 39.6% White. Out of this sample, 103 patients (44.7%) met DSM-IV criteria for a positive psychiatric history (n = 80) or a current psychiatric disorder (n = 43). A past history of depression (24%)exceeded the frequency of a history of other disorders (anxiety, 6%; alcohol use/abuse, 14%; drug use/abuse, 15%; adjustment, 23%; conduct disorders, 14%). Current mood disorders (47%) also exceeded other current diagnoses (anxiety, 9%; alcohol, 16%; drug, 7%; adjustment, 7%; personality disorders, 12%). Those with a current diagnosis were more likely to be unemployed (p CONCLUSIONS: Psychiatric comorbid disorders or a positive psychiatric history was found frequently in individuals with minor injury. An unplanned contact with the healthcare system (specifically an ED) for treatment of physical injury offers an opportunity for nurses to identify patients with psychiatric morbidity and to refer patients for appropriate therapy

Collection Of Field Data Using Wireless Instrumentation For Pump And System Evaluation

LectureThis paper outlines the benefits of utilizing a temporary data acquisition system with wireless instrumentation to collect field data for analysis and troubleshooting of pumps and pumping systems. It also discusses the basics of signal transmission with wireless system architecture and associated equipment. Two studies are given where a portable wireless data acquisition system was employed to support an analysis of a pumping system

Innovative Analyses Support a Role for DNA Damage and an Aberrant Cell Cycle in Myelodysplastic Syndrome Pathogenesis

We used flow cytometry to analyze the cell cycle, DNA damage, and apoptosis in hematopoietic subsets in MDS marrow. Subsets were assigned using CD45, side scatter, CD34, and CD71. Cell cycle fractions were analyzed using DRAQ 5 (DNA content) and MPM-2 (mitoses). DNA damage was assessed using p-H2A.X, and apoptosis using Annexin V. Compared to controls, MDS patients demonstrated no increased mitoses in erythroid, myeloid, or CD34+ cells. Myeloid progenitors demonstrated increased G2 cells, which with no increased mitoses suggested delayed passage through G2. Myeloid progenitors demonstrated increased p-H2A.X, consistent with DNA damage causing this delay. Annexin V reactivity was equivalent in MDS and controls. Results for each parameter varied among hematopoietic compartments, demonstrating the need to analyze compartments separately. Our results suggest that peripheral cytopenias in MDS are due to delayed cell cycle passage of marrow progenitors and that this delayed passage and leukemic progression derive from excessive DNA damage