ALBERT

Description: Recent studies have shown that flow cytometry immunophenotyping is a promising tool aiding in the diagnosis of myelodysplastic syndromes (MDS). However, the majority of these studies apply only qualitative pattern analysis in their interpretation of immunophenotypic data. The goal of this study was to analyze immunophenotyping results quantitatively, investigating the potential of this approach for providing additional information useful diagnosing MDS. Using flow cytometry immunophenotyping, we studied 56 bone marrow specimens from 13 patients with well-defined MDS by morphologic, clinical, and/or cytogenetic findings (5 RA, 3 RARS, 2 RAEB grade 1, 2 RAEB grade 2 and 1 secondary to chemotherapy), 15 cytopenic patients (controls, age-matched with MDS patients) with non-MDS/non-clonal hematologic disorders receiving marrow evaluation for other reason (ITP, fever of unknown origin, or lymphoma staging), 8 patients with AML transformed from MDS (t-AML), 6 patients with de novo AML, and 7 patients (14 specimens) with regenerating marrow after stem cell transplantation. These samples were analyzed qualitatively as reported in the literature as well as quantitatively for percentages of T-cells (CD3+), B-cells (CD20+), NK cells (CD3−/CD56+), granulocytes (moderate CD45 intensity and high side scatter characteristics), monocytes (CD14+/CD11c+), blasts (defined by dim CD45 and low side scatter, CD34+ or CD117+), erythroid precursors (CD71+/CD45−) and plasma cells (bright CD38), CD4/CD8 ratio, percentages of granulocyte subsets (CD10+, CD10−, CD36+/CD64+, CD36−/CD64+, CD11b−/CD16−, CD11b+/CD16− or CD11b+/CD16+ granulocytes per total granulocytes), percentage of CD56+ monocytes, and percentages of erythorid precursors subset (glycophorin A+ or glycophorin A- erythroid precursors per total erythroid precursors). In agreement with previous studies, qualitative analysis of these data demonstrated abnormal patterns of expression in myeloid and erythroid lineages in patients with MDS and t-AML. However, these patterns are also observed in age-matched controls and patients with de novo AML or with regenerating marrow. The quantitative analysis showed significantly increased T-cells and a significantly decreased granulocyte subset of CD11b+/CD16− in MDS patients when compared to age-matched controls (9.0 +/− 6.7% vs. 4.4 +/− 3.0 %, p = 0.023 and 28.1 +/− 14.9% vs. 44.5 +/−12.9%, p = 0.004, student t-test). There were also trends for increased NK cells and CD4:CD8 ratios and decreased total granulocytes in MDS patients as compared to the age-matched controls (p = 0.097, 0.094 and 0.059, respectively, student t-test). Other immunophenotypic parameters demonstrated no significant differences between these two groups. Furthermore, the changes observed in MDS patients were also seen in patients with t-AML. Patients with de novo AML or regenerating marrow post stem cell transplantation showed a quantitative immunophenotypic pattern between that of MDS patients and age-matched controls. These findings suggest that quantitative analysis of flow cytometry immunophenotyping data can aid in the diagnosis in MDS as well as the identification of AML arising from background MDS. The latter is clinically significant since these patients carry worse prognosis than those with de novo AML and may require novel therapies.

Description: Increasingly hemophiliacs are reaching ages where they acquire coronary artery disease (CAD) that necessitates consideration of coronary artery bypass grafting surgery (CABG). Treatment of vasculopathic hemophiliacs can be challenging in that there are no specific guidelines for this setting, particularly with respect to anticoagulant use. Detailed here are two cases of mild hemophilia who presented in 2003 with symptomatic, unstable CAD and who elected CABG. The first was a 48 year old man with CAD, unstable angina, hypertension, diabetes mellitus, hyperlipidemia, polycystic kidney disease, cigarette use, obstructive sleep apnea, obesity, and mild hemophilia-B that had manifested in his third decade as post-surgical hemorrhages. His factor IX activity had been measured at 20% and the inhibitor screening was negative. His body mass index was high (34). Cardiac catheterization demonstrated moderate to severe three-vessel stenoses with regional myocardial hypokinesis. Pre-CABG he was infused with a non-recombinant human factor IX dose [calculated at 80% of total body replacement (6,700 units)] per manufacturers infusion protocol. Within ten minutes of infusion the patient developed substernal chest pain radiating to the left arm, dyspnea, ischemic pattern on electocardiogram (EKG), bradycardia, hypotension, and unresponsiveness. Resuscitation attempts were immediately instituted but the patient expired. The second case was that of a 57 year old man with CAD, unstable angina, cigarette use, hyperlipidemia, obesity, rheumatoid arthritis, and mild hemophilia-A that had manifested in the past as easy bruisability and dental bleeding. His factor VIII activity was measured at 9% and the inhibitor screening was negative. Coronary catheterization revealed moderate to severe three-vessel stenoses. Pre-CABG the patient was infused simultaneously with recombinant human factor VIII {Caculated at 80% of total body replacement (5,000 units)] and unfractionated heparin (to keep partial thromboplastin time at 2.5 times the normal range) before being placed on the pump-oxygenator at surgery. A pentuple CABG (including an internal mammary artery graft) was performed without incident. Post-operatively factor VIII and unfractionated heparin infusion protocols were restarted. The heparin was discontinued prophylactically by the surgical team to prevent wound bleeding at three hours post-surgery. Within 90 minutes of heparin stoppage, the patient developed chest pain, ventricular arrhythmia, and EKG-troponin-creatine phosphokinase changes consistent with a sub-endocardial myocardial infarction. Heparin was immediately restarted and the remainder of the hospitalization was uneventful. In the two cases cited, mild hemophiliacs with unstable CAD suffered coronary thromboses when antihemophiliac factor therapy was unopposed by simultaneous anticoagulant therapy. We can find no previous approaches to this important scenario in the literature. Our experience here suggests that systematic, prospective study of anticoagulant protocol in vasculopathic hemophiliacs undergoing CABG is needed.

Description: We have analyzed GRACE Level 1-B data in 2003 and assessed a new approach for extracting time variable gravity that isolates the gravity signal in both time and space. The Level-1B satellite-to-satellite range rate (KBRR) data and accelerometry are processed in daily arcs using the precise orbit products produced by the GRACE team from GPS to calibrate both the accelerometer and KBRR data. We then adjusted select components of the intersatellite baseline vector for each data segment isolated to the region of interest. Herein, we solved for mass anomalies in 45 deg x 45 deg blocks over the Amazon and the nearby Atlantic Ocean and estimate mass flux in units of cm of water over each block. We show with this approach that we can recover mass anomalies on a submonthly basis with 10 to 15 day temporal resolution. We discuss the important issues related to this solution, including the size of the mascon blocks, the weight given to the temporal and spatial constraint used to stabalize the solutions, as well as the optimal correlation in time and distance. We compare the the mascon results with solutions obtained from the more standard approach using spherical harmonics and with independent hydrology models and lake data. This technique demonstrates that sub-monthly medium wavelength mass flux phenomena are well sensed by the hyper-precise line of sight velocity data produced from GRACE.