We hypothesized that in vitro treatment of peripheral blood mononuclear cells (PB-MNCs) from diabetic patients with ephrin-B2/Fc (EFNB2) improves their proangiogenic therapeutic potential in diabetic ischemic experimental models. Diabetes was induced in nude athymic mice by streptozotocin injections. At 9 weeks after hyperglycemia, 10(5) PB-MNCs from diabetic patients, pretreated by EFNB2, were intravenously injected in diabetic mice with hindlimb ischemia. Two weeks later, the postischemic neovascularization was evaluated. The mechanisms involved were investigated by flow cytometry analysis and in vitro cell biological assays. Paw skin blood flow, angiographic score, and capillary density were significantly increased in ischemic leg of diabetic mice receiving EFNB2-activated diabetic PB-MNCs versus those receiving nontreated diabetic PB-MNCs. EFNB2 bound to PB-MNCs and increased the adhesion and transmigration of PB-MNCs. Finally, EFNB2-activated PB-MNCs raised the number of circulating vascular progenitor cells in diabetic nude mice and increased the ability of endogenous bone marrow MNCs to differentiate into cells with endothelial phenotype and enhanced their proangiogenic potential. Therefore, EFNB2 treatment of PB-MNCs abrogates the diabetes-induced stem/progenitor cell dysfunction and opens a new avenue for the clinical development of an innovative and accessible strategy in diabetic patients with critical ischemic diseases.
A number of constitutively activated signaling pathways play critical roles in the survival and growth of primary effusion lymphoma cells (PELs) including NFkB and PI3/AKT kinase cascades. NFkBis constitutively activated in a number of malignancies, including multiple myeloma, Burkitt’s lymphoma and diffuse large cell B-cell lymphoma. However, its role in primary effusion lymphoma has not been fully explored.
The clinical importance of erythroid predominance in bone marrow of patients with acute myeloid leukemia (AML) is controversial. These cases represent a heterogeneous group of diseases that historically have been classified into different categories. We studied 313 AML patients and specifically compared the clinical, cytogenetic, and molecular features of cases of AML with erythroid predominance, arbitrarily defined as ≥50% erythroid precursors, to AML cases without erythroid predominance. We also assessed 51 patients with a high-grade myelodysplastic syndrome (MDS), refractory anemia with excess blasts (RAEB). All neoplasms were classified according to the World Health Organization classification. With the exception of therapy-related AML/MDS, the presence of erythroid predominance in variously classified categories of AML was associated with a survival advantage. In addition, AML with erythroid predominance had a lower frequency of cytogenetic abnormalities as well as a lower frequency of mutations involving NPM1, NRAS and FLT3 as compared with AML without erythroid predominance. We conclude that the clinical, cytogenetic, and molecular features of AML with erythroid predominance in the non-therapy-related setting are much closer to those of a high-grade myelodysplastic syndrome than they are to other types of AML.
Risk of Acute Leukemia and Myelodysplastic Syndromes in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS): a Population-Based Study of 17 315 Patients
- Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
- Published over 5 years ago
The purpose of this study was to determine if there is an increased risk of acute leukemia and myelodysplastic syndromes (MDS) in persons with monoclonal gammopathy of undetermined significance (MGUS). We utilized a large population-based cohort of individuals systematically screened for the presence or absence of MGUS. MGUS status was then linked to the diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and MDS. 17 315 patients age 50 and older (605 MGUS and 16 710 controls) with a cumulative 435 021 person-years of follow-up were studied. MGUS patients had a significantly higher risk of developing MDS compared with controls, hazard ratio 2.4 (95%CI 1.08,5.32), P=0.031. There was no statistically significant increase in the risk of AML (RR 1.36 P=0.675), and no increased risk of developing ALL.Leukemia accepted article preview online, 5 February 2013; doi:10.1038/leu.2013.34.
- Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række
- Published over 5 years ago
BACKGROUND Iron deficiency and iron deficiency anaemia are frequent problems in both the primary and the specialist health services. It is important to detect iron deficiency and to determine the causal relationship because iron deficiency may be secondary to a serious disease. The diagnosis of iron deficiency is largely based on biochemical and haematological laboratory findings, but there is no standardisation or consensus on the interpretation of these findings.METHOD Non-systematic search in the PubMed database with a discretionary selection of articles, based on the authors' knowledge of the field.RESULTS Ferritin measurement is the most important analysis in the study of iron deficiency, but there is no consensus on the diagnostic cut-off. It is usual in Norway today to use a ferritin level of < 12 - 20 μg/L, but at this low level the sensitivity for detecting iron deficiency is very low. A number of studies show that if the diagnostic cut-off is increased to the order of 30 μg/L the sensitivity is significantly higher for only a small reduction in specificity.INTERPRETATION When studying iron deficiency as a cause of anaemia, the diagnostic cut-off for detecting deficiency should be higher than that used today. The ferritin level increases with inflammation and ought in practice to be considered in conjunction with the CRP level. The level of transferrin receptor in plasma increases with iron deficiency without being influenced by inflammation and is therefore a good supplement to ferritin measurement. Measurement of iron, transferrin and transferrin saturation provides little information additional to that provided by ferritin in iron deficiency studies.
Hairy cell leukemia is a mature B-cell non-Hogkin lymphoma characterized by unique clinical, morphological and immunhistochemical features. Patients with hairy cell leukemia usually present with splenomegaly, progressive pancytopenia and a relative indolent clinical course. The diagnosis does not always indicate immediate treatment, as treatment depends on the clinical stage of the leukemia. Asymptomatic disease without progression requires a watchful waiting policy, while other categories usually need treatment. The treatment of choice is purin nucleosid analogues (pentostatin, cladribine) which can achieve complete remission even for decades. Interferon and monoclonal CD20 antibodies can also significantly prolong tevent free survival. Unfortunately, only the latter two therapies are easily available in Hungary. Splenectomy, which was suggested as first line treatment before the era of purin nucleosid analogues, is only recommended as ultimum refugium. Although hairy cell leukemia is a well-defined lymphoproliferative disease, sometimes it is difficult to differentiate it from other similar entities such as hairy cell leukema variant, splenic marginal zone lymphoma, small lymphocytic lymphoma etc. Making the correct diagnosis is of utmost importance because of the great difference in treatment modalities. Recently, a somatic mutation was found in all analysed hairy cell leukemia samples, but not in other splenic B-cell lymphomas. This article reviews the significance of this observation and presents the different types of methods for the detection of this mutation. Orv. Hetil., 2013, 154, 123-127.
The quantity of circulating reticulocytes is an important indicator of erythropoietic activity in response to a wide range of haematological pathologies. While most modern laboratories use flow cytometry to quantify reticulocytes, most field laboratories still rely on ‘subvital’ staining. The specialist ‘subvital’ stains, New Methylene Blue (NMB) and Brilliant Crésyl Blue are often difficult to procure, toxic, and show inconsistencies between batches. Here we demonstrate the utility of Giemsa’s stain (commonly used microbiology and parasitology) in a ‘subvital’ manner to provide an accurate method to visualize and count reticulocytes in blood samples from normal and malaria-infected individuals.
Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology has not been characterized when repeated blood loss occurs. Hepcidin was measured in plasma samples obtained from 114 first-time/reactivated (no blood donations in prior 2 years) female donors and 34 frequent (≥3 red blood cell donations in prior 12 months) male donors as they were phlebotomized ≥4 or more times over 18-24 months. Hepcidin was compared to ferritin and hemoglobin using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin correlated well with each other (Spearman correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (≤45.7 ng/ml) or decreasing hepcidin and low ferritin (≤26 ng/ml), and was essentially zero for other subjects including those with high (>45.7 ng/ml) or increasing hepcidin and low ferritin (≤26 ng/ml) (p<0.001). Hepcidin rapidly changes in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of low ferritin suggests that plasma hepcidin may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone.
Paradoxical embolism (PDE) occurs after embolic material passes from the venous to the arterial circulation through a right-to-left shunt, which is frequently a patent foramen ovale (PFO). We describe the case of a patient with deep venous thrombosis and an intracardiac thrombus straddling a PFO and who was successfully treated with an emergency surgery.
Arterial spin labeling (ASL) techniques are gaining popularity for visualizing and quantifying cerebral blood flow (CBF) in a range of patient groups. However, most ASL methods lack vessel-selective information, which is important for the assessment of collateral flow and the arterial supply to lesions. In this study, we explored the use of vessel-encoded pseudocontinuous ASL (VEPCASL) with multiple postlabeling delays to obtain individual quantitative CBF and bolus arrival time maps for each of the four main brain-feeding arteries and compared the results against those obtained with conventional pseudocontinuous ASL (PCASL) using matched scan time. Simulations showed that PCASL systematically underestimated CBF by up to 37% in voxels supplied by two arteries, whereas VEPCASL maintained CBF accuracy since each vascular component is treated separately. Experimental results in healthy volunteers showed that there is no systematic bias in the CBF estimates produced by VEPCASL and that the signal-to-noise ratio of the two techniques is comparable. Although more complex acquisition and image processing is required and the potential for motion sensitivity is increased, VEPCASL provides comparable data to PCASL but with the added benefit of vessel-selective information. This could lead to more accurate CBF estimates in patients with a significant collateral flow.Journal of Cerebral Blood Flow & Metabolism advance online publication, 7 August 2013; doi:10.1038/jcbfm.2013.129.