7.0?T MRI detection of cerebral microinfarcts in patients with a symptomatic high-grade carotid artery stenosis

In the current study, the presence of cerebral cortical microinfarcts (CMIs) was evaluated in a series of 21 patients with a symptomatic high-grade >50% stenosis of the carotid artery. A T₂-weighted fluid-attenuated inversion recovery sequence and a T₁-weighted turbo field echo sequence of the brain were obtained at 7.0 Tesla magnetic resonance imaging. Primary study endpoint was the number of CMIs and macroinfarcts. In total, 53 cerebral infarcts (35 macroinfarcts; 18 CMIs) were found ipsilateral to the symptomatic carotid artery, in 14 patients (67%). In four of these patients, both CMIs and macroinfarcts were visible. In the contralateral hemisphere, seven infarcts (five macroinfarcts and two CMIs) were found in five patients (24%). In the ipsilateral hemispheres, the number of CMIs and macroinfarcts were significantly correlated (P=0.02). Unpaired comparison of medians showed that the number of CMIs in the ipsilateral hemisphere was significantly higher than the number of CMIs in the contralateral hemisphere (P=0.04). No significant correlation was found between stenosis grade and the number of any infarct. The current study shows that in symptomatic patients with significant extracranial carotid artery stenosis, CMIs are part of the total cerebrovascular burden and these CMIs prevail with a similar pattern as observed macroinfarcts.     

Unicellular or multicellular origin of human granulocyte-macrophage colonies in vitro

The assumption that human granulocyte-macrophage colonies have a unicellular origin and thus are true clones has been directly tested. Cells from seven females heterozygous for the common glucose-6- phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA were cultured in semisolid medium for granulocyte-macrophage colony growth and the enzyme type of individual colonies was determined. When the colony density was less than 20/dish, more than 95% of colonies had either type A or type B G-6-PD, but not both. At colony densities greater than 30/dish, between 15% and 75% of colonies had both enzyme types and therefore arose from more than one cell. These results are consistent with a unicellular origin for the colonies only when they are cultured at low densities. With increasing colony density, there was a greater frequency of colonies with both type A and type B activity, suggesting that accurate enumeration of committed stem cells can only be performed at low colony concentrations.     

Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry

The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma cells were located in a unique position in the correlation of forward light scattering, orthogonal light scattering, and immunofluorescent-labeled CD38. The identity of the sorted cell populations was confirmed by microscopic examination of Wright's stained slides and slides stained for cytoplasmic immunoglobulin using polyclonal antibodies reactive with light chains; ie, anti-kappa fluorescein isothiocyanate and anti lambda phycoerythrin (PE). The purity of the sorted plasma cells was greater than 97% (n = 4). The average frequency of plasma cells in normal bone marrow aspirates was low--0.25% of the nucleated cells (n = 7)--but surprisingly consistent between individuals (SD = .05; range 0.14% to 0.30%). A detailed analysis showed two distinct populations of plasma cells: (1) A population relatively smaller by forward light scattering expressed CD22, CD35, and sigE and was identified as early plasma cells (ie, lymphoplasmacytoid), and (2) a population larger by forward light scattering lacked these markers and was identified as mature plasma cells. The antigenic profile of the normal plasma cells was determined in two-color immunofluorescence studies. The expression of cell surface immunoglobulin G (IgG), IgA, IgE, IgD, IgM, and the cell surface antigens CD10, CD11b, CD13, CD11c, CD14, CD15, CD16, CD19, CD22, CD20, CD33, CD35, CD45, and HLA-DR was determined on the plasma cells. A significant heterogeneity in cell surface antigen expression was observed within the plasma cell population. Unexpectedly, myeloid- specific cell surface antigens such as CD33 and CD13 and the early B- cell antigen identified by CD10 were expressed on a proportion of plasma cells. These observations imply that the association of myeloid and early B-cell markers described in multiple myeloma may not be associated with the neoplasia but is a normal phenomenon.     

Peripheral blood harvest of unaffected CD34+ CD38- hematopoietic precursors in paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) arises from somatic mutation of a bone marrow progenitor that disrupts glycosylinositol phospholipid (GPI) anchoring of cell surface proteins. We recently characterized the expression of GPI-anchored decay acclerating factor (DAF) and CD59 during hematopoietic development in PNH marrow. We found that, although a subset of early hematopoietic precursors identified by the CD34+CD38- phenotype exhibits normal DAF and CD59 expression, DAF and CD59 are absent on the majority of CD34+CD38- cells. Pluripotent CD34+CD38- hematopoietic stem cells normally circulate in the peripheral blood and can be collected by apheresis, cryopreserved, and later used for reconstitution of hematopoiesis. In this study, we examined the phenotypes of CD34+ cells that are released into the blood of PNH patients. Analyses of apheresis samples from three affected individuals showed discrete populations of circulating DAF+CD59+CD34+ and DAF-CD59- CD34+ cells. Variable proportions of CD34+CD38- cells were present within the peripheral blood CD34+ cells of each patient, but in all three cases the DAF+CD59+CD34+CD38- cell subset subset. Because CD34+ cells lacking CD38 antigen are highly enriched for self-renewing hematopoietic stem cells, these findings indicate that apheresis samples can serve as a source of unaffected stem cells for autologous marrow transplantation of PNH patients.     

Harvesting and enrichment of hematopoietic progenitor cells mobilized into the peripheral blood of normal donors by granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF: potential role in allogeneic marrow transplantation

To explore the use of stem/progenitor cells from peripheral blood (PB) for allogeneic transplantation, we have studied the mobilization of progenitor cells in normal donors by growth factors. Normal subjects were administered either granulocyte-macrophage colony-stimulating factor (GM-CSF) at 10 micrograms/kg/d, or G-CSF at 10 micrograms/kg/d, or a combination of G- and GM-CSF at 5 micrograms/kg/d each, administered subcutaneously for 4 days, followed by leukapheresis on day 5. Mononuclear cells expressing CD34 (CD34+ cells) were selectively enriched by affinity labeling using Dynal paramagnetic microspheres (Baxter Isolex; Baxter Healthcare Corp, Santa Ana, CA). The baseline CD34+ cells in peripheral blood before mobilization was 0.07% +/- 0.05% (1.6 +/- 0.7/microL; n = 18). On the fifth day after stimulation (24 hours after the fourth dose), the CD34+ cells were 0.99% +/- 0.40% (61 +/- 14/microL) for the 8 subjects treated with G-CSF, 0.25% +/- 0.25% (3 +/- 3/microL, both P < .01 v G-CSF) for the 5 subjects administered GM-CSF, and for the 5 subjects treated with G- and GM-CSF, 0.65% +/- 0.28% (41 +/- 18/microL, P < .5 v GM-CSF). Parallel to this increase in CD34+ cells, clonogenic assays showed a corresponding increase in CFU- GM and BFU-E. The total number of CD34+ cells collected from the G-CSF group during a 3-hour apheresis was 119 +/- 65 x 10(6) and was not significantly different from that collected from the group treated with G- and GM-CSF (101 +/- 35 x 10(6) cells), but both were greater than that from the group treated with GM-CSF (12.6 +/- 6.1 x 10(6); P < .01 for both comparisons). Analysis of the CD34+ subsets showed that a significantly higher percentage of cells with the CD34+/CD38- phenotype is found after mobilization with G- and GM-CSF. In the G-CSF group, immunomagnetic selection of CD34+ cells permitted the enrichment of the CD34+ cells in the apheresis product to 81% +/- 11%, with a 48% +/- 12% yield and to a purity of 77% +/- 21% with a 51% +/- 15% recovery in the G- and GM-CSF group. T cells were depleted from a mean of 4.5 +/- 2.0 x 10(9) to 4.3 +/- 5.2 x 10(6) after selection, representing 99.9% depletion. We conclude that it is feasible to collect sufficient numbers of PB progenitor cells from normal donors with one to two leukapheresis procedures for allogeneic transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multislice 1H MRSI of the human brain at 7 T using dynamic B0 and B1 shimming

Proton MR spectroscopic imaging of the human brain at ultra-high field (≥7 T) is challenging due to increased radio frequency power deposition, increased magnetic field B(0) inhomogeneity, and increased radio frequency magnetic field inhomogeneity. In addition, especially for multislice sequences, these effects directly inhibit the potential gains of higher magnetic field and can even cause a reduction in data quality. However, recent developments in dynamic B(0) magnetic field shimming and dynamic multitransmit radio frequency control allow for new acquisition strategies. Therefore, in this work, slice-by-slice B(0) and B(1) shimming was developed to optimize both B(0) magnetic field homogeneity and nutation angle over a large portion of the brain. Together with a low-power water and lipid suppression sequence and pulse-acquire spectroscopic imaging, a multislice MR spectroscopic imaging sequence is shown to be feasible at 7 T. This now allows for multislice metabolic imaging of the human brain with high sensitivity and high chemical shift resolution at ultra-high field.     

Improving SNR and B1 transmit field for an endorectal coil in 7 T MRI and MRS of prostate cancer

Higher magnetic field strengths like 7 T and above are desirable for MR spectroscopy given the increased spectral resolution and signal to noise ratio. At these field strengths, substantial nonuniformities in B(1)(+/-) and radiofrequency power deposition become apparent. In this investigation, we propose an improvement on a conventionally used endorectal coil, through the addition of a second element (stripline). Both elements are used as transceivers. In the center of the prostate, approximately 40% signal to noise ratio increase is achieved. In fact, the signal to noise ratio gain obtained with the quadrature configuration locally can be even greater than 40% when compared to the single loop configuration. This is due to the natural asymmetry of the B(1)(+/-) fields at high frequencies, which causes destructive and constructive interference patterns. Global specific absorption rate is reduced by almost a factor of 2 as expected. Furthermore, approximately a 4-fold decrease in local specific absorption rate is observed when normalized to the B(1) values in the center of the prostate. Because of the 4-fold local specific absorption rate decrease obtained with the dual channel setup for the same reference B(1) value (20 μT at 3.5 cm depth into the prostate) as compared to the single loop, the transmission power B(1) duty cycle can be increased by a factor 4. Consequently, when using the two-element endorectal coil, the radiofrequency power deposition is significantly reduced and radiofrequency intense sequences with adiabatic pulses can be safely applied at 7 T for (1)H magnetic resonance spectroscopy and MRI in the prostate. Altogether, in vivo (1)H magnetic resonance spectroscopic imaging of prostate cancer with a fully adiabatic sequence operated at a minimum B(1)(+) of 20 μT shows insensitivity to the nonuniform transmit field, while remaining within local specific absorption rate guidelines of 10 W/kg.     

注射用右兰索拉唑治疗急性胃和/或十二指肠溃疡引起的上消化道出血的有效性及安全性

目的：以注射用兰索拉唑为对照,评价注射用右兰索拉唑15 mg q12 h治疗急性胃和/或十二指肠溃疡引起的上消化道出血的有效性及安全性。方法：选取全国31家研究中心的急性胃和/或十二指肠溃疡引起的上消化道出血患者共202例,按照1∶1随机分配至试验组（注射用右兰索拉唑组）和对照组（注射用兰索拉唑组）。主要疗效终点为72 h有效止血率。对主要疗效终点采用非劣效评价,非劣效性界值δ是10%。结果：有效性方面,全分析数据集分析结果显示：用药72 h后,注射用右兰索拉唑组有效止血率为96.08%(98/102);注射用兰索拉唑组有效止血率为98.00%(98/100),两组率差为-1.92%(95%CI-6.58,2.74)。两组72 h有效止血率差异无统计学意义（P=0.682 9）。两组率差的双侧界值均低于δ(10%),注射用右兰索拉唑非劣于注射用兰索拉唑。安全性方面,试验组的不良事件及不良反应发生率与对照组差异无统计学意义,无非预期不良反应和严重不良反应。主要的不良反应为白细胞计数降低、中性粒细胞计数降低等。结论：注射用右兰索拉唑15 mg q12 h在治疗急性胃和/或十二指肠溃疡引起的...