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  • 1
    Language: English
    In: Radiology, April 2016, Vol.279(1), pp.306-13
    Description: To define height- and sex-corrected normal values for spleen length and volume determined with ultrasonography (US). The authors performed a retrospective data review of stem cell donors who had provided written informed consent for stem cell donation and use of anonymized data and biologic materials for scientific and quality control purposes. Spleen length, spleen volume, and anthrophometric data were correlated in 1230 healthy volunteers to identify variables that affect spleen size. Multiple linear regression analysis was performed to weight effects of various variables on spleen size. Linear regression through the 95th percentile for men and women of different height cohorts generated the formula for the upper limit of normal for spleen length and volume. For validation, the upper limit of normal was calculated for each volunteer and compared with the observed value. Formulae to calculate the additional percentiles were similarly generated and validated. A cohort of 75 volunteers was analyzed twice to assess the stability of spleen length and volume over time. Spleen length and volume were significantly and independently associated with sex (length: P 〈 .001; volume: P = .012), body height (P 〈 .001 for both), and weight (P 〈 .001 for both), with men and taller and heavier individuals having longer and larger spleens. The spleen length of 20 of 324 women (6%) and 234 of 906 men (26%) exceeded the previously reported upper limit of normal of 12 cm. Repeat measurements indicated that spleen length (median difference, 0.10 cm; range, -1.8 to 1.7 cm) and volume (median difference, 3 cm(3); range, -106 to 142 cm(3)) were quite stable. A mobile application that performs these calculations is available for download. The authors define height- and sex-corrected normal values for spleen length and volume for women with a body height of 155-179 cm and men with a body height of 165-199 cm and propose validated algorithms to gauge the percentile of an individual's spleen size.
    Keywords: Spleen -- Anatomy & Histology
    ISSN: 00338419
    E-ISSN: 1527-1315
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  • 2
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(3), p.e0121859
    Description: The genetics responsible for the inter-individually variable G-CSF responsiveness remain elusive. A single nucleotide polymorphism (SNP) in the 3'UTR of CXCL12, rs1801157, was implicated in X4-tropic HiV susceptibility and later, in two small studies, in G-CSR responsiveness in patients and donors. The position of the SNP in the 3'UTR together with in-silico predictions suggested differential binding of micro-RNA941 as an underlying mechanism. In a cohort of 515 healthy stem cell donors we attempted to reproduce the correlation of the CXCL12 3'UTR SNP and mobilization responses and tested the role of miR941 in this context. The SNP was distributed with the expected frequency. Mobilization efficiency for CD34+ cells in WT, heterozygous and homozygous SNP individuals was indistinguishable, even after controlling for gender. miR941 expression in non-hematopoietic bone marrow cells was undetectable and miR941 did not interact with the 3' UTR of CXCL12. Proposed effects of the SNP rs1801157 on G-CSF responsiveness cannot be confirmed in a larger cohort.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 3
    In: STEM CELLS, August 2015, Vol.33(8), pp.2391-2399
    Description: Dominant, although nonexclusive roles of CXCR4 and its chief ligand CXCL12 in bone marrow (BM) retention and preservation of the relative quiescence of hematopoietic stem/progenitor cells (HSPCs), along with their involvement in human immunodeficiency virus infection, in trafficking of mature hematopoietic cells to sites of inflammation and in orderly migration of nonhematopoietic cells during embryogenesis, explain the significant interest of the scientific community in the mode of action of this receptor–ligand pair. In this focused review, we seek to distil from the large body of information that has become available over the years some of the key findings about the role of CXCR4/CXCL12 in normal immature hematopoiesis. It is hoped that understanding the mechanistic insights gained there from will help generate hypotheses about potential avenues in which cancer/leukemia cell behavior can be modified by interference with this pathway. S C
    Keywords: Adult Hematopoietic Stem Cells ; Chemokine Receptors ; Bone Marrow Stromal Cells ; Cell Adhesion Molecules ; Cell Cycle ; Cell Migration ; Cell Transplantation ; Chemokine
    ISSN: 1066-5099
    E-ISSN: 1549-4918
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  • 4
    In: Current Opinion in Hematology, 2016, Vol.23(1), pp.61-66
    Description: PURPOSE OF REVIEW: With the approval of the first biosimilar granulocyte colony-stimulating factor (G-CSF), biosimilars – copies of therapeutic biologicals whose patent protection has expired – have finally reached the US healthcare market. Its advent is an occasion for a closer look at recent insights into biosimilar G-CSF and an attempt at prognosticating the future (future role) of biosimilars in general. RECENT FINDINGS: Recent literature regarding biosimilar G-CSF orbits significantly around patient access and effects on healthcare expenditure. The advent of biosimilar G-CSF has induced unexpectedly large price reductions for short-acting G-CSF. On the clinical side, little excitement is tangible, probably appropriately so, since clinical data indicate nothing short of biological similarity. Although formal clinical trials are few, the plethora of case series and historic comparisons which have come forth offer reassurance about the appropriateness of the regulators’ assessment of biosimilar G-CSF as indeed in all respects biologically similar to the originator. SUMMARY: All evidence points to an overwhelming similarity of originator and biosimilar G-CSF in all indications. Overall clinical acceptance, albeit possibly significantly dictated by economic pressures, is good. Price reductions exceed predictions and may jeopardize the economic viability of biosimilar programs. A concurrent shift towards long-acting G-CSF (‘biobetters’) is observed in Europe.
    Keywords: Biosimilar Pharmaceuticals–Pharmacology ; Clinical Studies As Topic–Therapeutic Use ; Cost-Benefit Analysis–Pharmacology ; Granulocyte Colony-Stimulating Factor–Therapeutic Use ; Humans–Therapeutic Use ; Licensure–Therapeutic Use ; Treatment Outcome–Therapeutic Use ; Biosimilar Pharmaceuticals ; Granulocyte Colony-Stimulating Factor;
    ISSN: 1065-6251
    E-ISSN: 15317048
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  • 5
    Language: English
    In: Transfusion and Apheresis Science, October 2018, Vol.57(5), pp.628-634
    Description: Leukapheresis is like any other preparative apheresis, except it isn’t: Leukapheresis typically takes much longer, larger blood volumes are processed and, consequently, larger ACD-A volumes are administered. Blood component donors and leukapheresis subjects are also quite different populations. Allogeneic donors tend to be younger and many are first-time donors, both of which are risk factors for adverse reactions during blood donation. Moreover, more than half of all leukapheresis collections are performed in patients. Here it is the age distribution, including patients at the extremes of age, as well as the underlying disease and co-morbidities which may expose them to higher, or different, risks compared to donors. Both groups thus have good reasons why adverse effects to leukapheresis might be more frequent, more severe, or even different in nature altogether. Compared to other preparative apheresis types like platelet or plasma apheresis, the risks of leukapheresis have been studied less extensively, as it is in comparison a relatively low-frequency intervention. Often leukapheresis remains a domain of hematologists who have a different sense of procedural safety than transfusionists. Furthermore, G-CSF mobilized “stem cell” aphereses by a wide margin outnumber unmobilized aphereses, so that the very strong signal from adverse reactions to G-CSF all but drowns out signals from the apheresis proper. This focused review assesses observations from leukapheresis as well as extrapolation of observations from other forms of preparative apheresis in an attempt to gauge the safety of leukapheresis and identify potential approaches to its further improvement. In short, the overall impression is one of a very satisfactory safety record of leukapheresis, with occasional issues with venous access or vasovagal problems, and frequent, but highly responsive and rarely limiting ACD-A toxicity.
    Keywords: Leukapheresis ; Apheresis Safety ; Apheresis Risks ; Component Donor ; Blood Donor ; Medicine
    ISSN: 1473-0502
    E-ISSN: 1878-1683
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  • 6
    In: Cerebral Cortex, 2016, Vol. 26(4), pp.1539-1557
    Description: Choosing and implementing the rules for contextually adequate behavior depends on frontostriatal interactions. Observations in Parkinson's disease and pharmacological manipulations of dopamine transmission suggest that these corticobasal loops are modulated by dopamine. To determine, therefore, the physiological contributions of dopamine to task-rule–related processing, we performed a cue–target fMRI reading paradigm in 71 healthy participants and investigated the effects of COMT Val158Met, DAT1 VNTR 9/10, and DRD2/ANKK1 polymorphisms. The DRD2/ANKK1 polymorphism did not affect results. Intermediate prefrontal dopamine concentrations in COMT Val158Met heterozygotes facilitated preparatory interactions between the mesial prefrontal cortex and the left striatum during preparation for overt reading. To our knowledge, this is the first report of an inverted U-shaped curve modulation of cognition-related brain activity by prefrontal dopamine levels. In contrast, a linear effect of COMT Val158Met and DAT1 VNTR 9/10 polymorphisms on preparatory activity in the left inferior frontal gyrus pointed to a negative interaction between tonic lateral prefrontal and phasic subcortical dopamine. The COMT Val158Met polymorphism affected also feedforward and feedback processing in the sensorimotor speech system. Our results suggest that dopamine modulates corticobasal interactions on both the cortical and subcortical level but differently depending on the specific cognitive subprocesses involved.
    Keywords: Comt Val158met ; Dat1 Vntr 9/10 ; Fmri ; Inverted U - Shaped Curved Cortical—Subcortical Interactions ; Speech Production
    ISSN: 1047-3211
    E-ISSN: 1460-2199
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  • 7
    In: PLoS ONE, 2016, Vol.11(8)
    Description: High hydrostatic pressure has been used to inactivate pathogens in foods for decades. There is a great potential to adapt this technology to inactivate pathogens in plasma and derivatives. To better evaluate the potential of this method, pathogen inoculated plasma samples were pressurized under different pressure application modes and temperatures. The inactivation efficacy of pathogens and activities of plasma proteins were monitored after treatment. The CFUs of E . coli was examined as the indicator of the inactivation efficiency. The factor V and VIII were chosen as the indicator of the plasma function. Preliminary experiments identified optimized treatment conditions: 200-250MPa, with 5×1 minute multi-pulsed high pressure at near 0°C (ice-water bath). Under this conditions, the inactivation efficacy of EMCV was 〉8.5log. The CFUs of E . coli were reduced by 7.5log, B . cereus were 8log. However, PPV and S . aureus cannot be inactivated efficiently. The activities of factor II, VII, IX, X, XI, XII, fibrinogen, IgG, IgM stayed over 95% compared to untreated. Factor V and VIII activity was maintained at 46–63% and 77–82%, respectively.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Physical Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 8
    In: PLoS ONE, 2017, Vol.12(5)
    Description: Febrile neutropenia (FN) is a medical emergency and can represent a life-threatening complication for hematology patients treated with intensive chemotherapy regimens. In clinical practice, the diagnostic yield of blood cultures and other investigations which aim to identify a causative organism or site of infection is low. We have retrospectively examined all blood cultures collected in a “real world” cohort of patients receiving chemotherapy for acute leukemia and patients with aggressive lymphoma treated with Hyper-CVAD/MTX-cytarabine, at a single tertiary center over a five-year period. In this cohort, the 30-day mortality following confirmed blood stream infection (BSI) was 5.9%, which is lower than most reports in the recent literature. We compared the blood culture results of inpatients undergoing induction chemotherapy and outpatients presenting with fevers and found a significantly higher rate of proven BSI in the outpatient group. In all settings, gram-negative organisms were most common. The rate of resistance to first-line empiric antibiotics among pathogenic isolates was 11.6% in the whole cohort, independent of blood culture circumstances. There was a trend to higher resistance rates among inpatients undergoing induction chemotherapy compared to patients presenting to the emergency department (17.4% vs 7.5%) but this did not reach statistical significance. We also report low rates of ciprofloxacin resistance (5% of isolates), in a center where universal fluoroquinolone prophylaxis is not employed. Our low resistance and mortality rates support our current therapeutic strategies, however presence of resistant organisms across the spectrum of indications for BC collection highlights the importance of surveilling local patterns, escalating antimicrobial therapy in the deteriorating patient, and considering advanced techniques for the rapid identification of resistance in this patient population.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; People And Places ; Medicine And Health Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences ; Medicine And Health Sciences
    E-ISSN: 1932-6203
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  • 9
    Article
    Article
    In: Transfusion, October 2014, Vol.54(10), pp.2585-2586
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/trf.12810/abstract Byline: Miriam Schulz, Halvard Bonig ***** No abstract is available for this article. *****
    Keywords: Blood Component Removal -- Methods ; Leukapheresis -- Methods;
    ISSN: 0041-1132
    E-ISSN: 1537-2995
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  • 10
    Language: English
    In: Cytotherapy, October 2016, Vol.18(10), pp.1345-1347
    Keywords: T-Cell Depletion ; Stem Cell Transplantation ; Graft Manipulation ; Immunomagnetic ; Bone Marrow ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 1465-3249
    E-ISSN: 1477-2566
    Source: ScienceDirect Journals (Elsevier)
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