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  • JAMA February 17, 2015

    Figure 2: Changes in the Primary End Point of Spleen Volume in the Intention-to-Treat Population

    For absolute mean changes in spleen volume, error bars indicate 95% CIs. For individual baseline and 9-month values for each patient, patients are ordered in each graph from the lowest to the highest baseline value. Mean baseline values for spleen volume were as follows: for eliglustat, 13.9 multiples of normal, and placebo, 12.5 multiples of normal.aIndicates the single patient who withdrew from the trial; this patient in the eliglustat group withdrew for personal reasons at 3 months and had no 6-month or 9-month assessments. For the final efficacy assessments, change for this patient was determined by last observation carried forward; thus, for spleen volume, the baseline value was carried forward.
  • Effect of Oral Eliglustat on Splenomegaly in Patients With Gaucher Disease Type 1: The ENGAGE Randomized Clinical Trial

    Abstract Full Text
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    JAMA. 2015; 313(7):695-706. doi: 10.1001/jama.2015.459

    This international randomized clinical trial found that among adults with Gaucher disease type 1, treatment with eliglustat for 9 months resulted in significant improvements in spleen volume, hemoglobin level, liver volume, and platelet count compared with placebo.

  • JAMA December 21, 2011

    Figure 5: Immune Effector Cells in Spleen Tissue

    Spleen from sepsis patients (n = 22) or nonsepsis controls (n = 12) was stained for HLA-DR, CD4, or CD8 and examined by an investigator (P.E.S.) blinded to sample identity (eAppendix). 3,3′-diaminobenzidine 4-HCl was used as a chromogen to stain the cells of interest (brown), and a hematoxylin counterstain (blue) was used for background staining. A (HLA-DR immunostain; 200×), In a representative control sample, HLA-DR immunoreactivity is robust in all periarteriolar T- and B-cell zones, consistent with major histocompatibility complex (MHC) II pattern 2A (see reference 42 and eTable 7). There is marked loss of HLA-DR reactivity in B and T lymphocytes typical of nearly subtotal depletion of HLA-DR–reactive elements in sepsis (MHC II pattern 4). Note that sinusoidal endothelium staining is pronounced, a change seen only in sepsis. B (CD4 immunostain; 400×), Periarteriolar CD4 cells are quantitatively decreased in sepsis (right panel) relative to control (left panel). C (CD8 immunostain; 400×), Periarteriolar CD8 cells are also quantitatively decreased in sepsis (right panel) relative to controls (left panel). D, The dot plots are cell counts for CD4 and CD8 T cells, obtained by counting number of cells per field in periarteriolar lymphoid sheaths. Two fields were counted per slide and averaged. Statistical analysis was performed using a nonparametric 2-tailed Mann-Whitney U test. Each data marker represents an individual patient. Horizontal bars represent mean values.
  • Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure

    Abstract Full Text
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    JAMA. 2011; 306(23):2594-2605. doi: 10.1001/jama.2011.1829
  • JAMA December 21, 2011

    Figure 1: Cytokine Secretion in Stimulated Splenocytes

    Spleens were harvested from patients who died of sepsis (n = 24-26) or nonsepsis etiologies (n = 20-21). Cells were dissociated and washed and viability determined by trypan blue exclusion. Viable splenocytes (1 × 107) were stimulated with lipopolysaccharide or anti-CD3/anti-CD28 antibody. Supernatants were harvested at 5 and 22 hours and tumor necrosis factor (TNF), interferon γ (IFN-γ), and interleukins (IL) 6 and 10 were measured by enzyme-linked immunosorbent assay. There was a marked decrease in cytokine secretion in sepsis patients vs nonsepsis controls. Data were analyzed by 2-tailed nonparametric t test (Mann-Whitney U test). Each data marker represents an individual patient. Horizontal lines represent mean values. P <.001 for all plots, except P <.01 for TNF with lipopolysaccharide stimulation at 22 hours.
  • JAMA December 21, 2011

    Figure 2: Expression of Cell Surface Receptors on Splenic CD4 and CD8 T Cells

    See Figure 3 legend for explanation of geo-mean fluorescence intensity units, laboratory methods and statistical analysis. Compared with nonsepsis controls (n = 24-26), sepsis patients (n = 28-31) had activated T cells (increased CD69 in CD4 and CD8 T cells as well as increased CD25 [interleukin {IL} 2 receptor α] in CD4 T cells). Despite an activation phenotype, sepsis induced down-regulation of positive costimulatory receptors (CD28 in CD4 and CD8 T cells) as well as increased inhibitory receptors (programmed cell death 1 [PD-1] for CD4 T cells and cytotoxic T-lymphocyte antigen 4 [CTLA-4] for CD8 T cells). The IL-7 receptor α chain (CD127) was decreased in CD4 and CD8 T cells in sepsis.
  • JAMA December 21, 2011

    Figure 3: Expression of Cell Surface Receptors on Splenic Antigen-Presenting Cells and Tissue Macrophages

    Splenocytes (2 × 106) were stained with fluorescently conjugated antibodies or isotype-matched control antibodies and analyzed by flow cytometry (eAppendix). A positive gate was established based on isotype control staining. The percentage positive for each marker was defined by subtracting the percentage within the positive gate in the isotype control from the percentage within the positive gate in the specific stain. The geo-mean fluorescence intensity was determined by subtraction of the nonspecific fluorescence of the isotype control antibody from the fluorescence of the specific conjugated antibody and is expressed in units, which are an average of fluorescence intensity of the data collected within the selected gate after subtracting fluorescence intensity of isotope control. Antigen-presenting cells, ie, dendritic cells and macrophages/monocytes, as well as tissue-specific macrophages, showed an immunosuppressive phenotype in sepsis as evidenced by decreased expression of CD86 and HLA-DR. In addition, antigen-presenting cells from sepsis patients had increased expression of PD-L1, the ligand for the inhibitory receptor programmed cell death 1 PD-1 on T cells. Each data marker represents an individual patient. Statistical analysis was performed by 2-tailed nonparametric t test (Mann-Whitney U test). Horizontal lines represent mean values.
  • The Spleen

    Abstract Full Text
    JAMA. 2005; 294(20):2660-2660. doi: 10.1001/jama.294.20.2660
  • JAMA July 14, 2004

    Figure 2: Computed Tomographic Scan of Liver With and Without Contrast

    A, Noncontrast computed tomographic scan of the patient that was performed to look for fatty infiltration of the liver, which is associated with nucleoside analogue hepatotoxicity. With fatty infiltration, the liver is diffusely low in density compared with the spleen. In this patient, region-of-interest measurements in the liver have a density of 57, similar to that of the spleen, which measures 57 Hounsfield units. These results are inconsistent with substantial fatty infiltration of the liver, suggesting that the nucleoside analogues were not playing a major role in the increase in this patient's alanine aminotransferase and aspartate aminotransferase levels. B, The postcontrast scan, obtained during arterial and portal phases of flow, showed no evidence of a mass lesion.
  • JAMA November 23, 2005

    Figure: The Spleen

  • JAMA August 26, 1998

    Figure: Spleen (No. 78)

  • JAMA May 27, 1998

    Figure: Spleen (No. 77)

  • JAMA May 20, 1998

    Figure: Spleen (No. 76)

  • JAMA March 18, 1992

    Figure: The Spleen

  • Spleen (No. 78)

    Abstract Full Text
    JAMA. 1998; 280(8):674B-674B. doi: 10.1001/jama.280.8.674
  • Spleen (No. 77)

    Abstract Full Text
    JAMA. 1998; 279(20):1590B-1590B. doi: 10.1001/jama.279.20.1590
  • Spleen (No. 76)

    Abstract Full Text
    JAMA. 1998; 279(19):1508Q-1508Q. doi: 10.1001/jama.279.19.1508
  • The Flowers of Evil and Paris Spleen

    Abstract Full Text
    JAMA. 1992; 268(12):1603-1603. doi: 10.1001/jama.1992.03490120117043