The Geneva prognostic score and mortality in patients diagnosed with pulmonary embolism by CT pulmonary angiogram

This study prospectively evaluates whether a previously established adverse outcome score (the Geneva prognostic score) predicts 3 and 12‐month overall mortality among the patients diagnosed with pulmonary embolism (PE) by a CT pulmonary angiogram (CTPA). Five hundred twenty‐three consecutive patients who had CTPA for suspected PE were recruited prospectively from March 2003 to October 2004. The Geneva prognostic score was calculated for all patients. Twelve‐month follow up was completed in all patients in December 2005. There were 105 patients diagnosed with PE. The mean score was 2.71 (standard deviation (SD) 1.25) for those patients who had died (n = 7) and 1.14 (SD 1.19) for those patients who were alive (n = 98) at 3‐month follow up (P < 0.001). The mean scores were 2.69 (SD 0.95) for those who had died (n = 13) and 1.04 (SD 1.15) for those patients who were alive (n = 92) at 12‐month follow up (P < 0.001). At 3‐month follow up, among the 88 patients with a score of 2 or less, three patients (3.4%) died and among 17 patients with a score of greater than 2, four patients (23.5%) died (P = 0.01). At 12‐month follow up, five patients (5.7%) with a score of 2 or less died and eight patients (47.1%) with a score of three or more died (P < 0.0001). The Geneva prognostic score stratifies patients with low and high risk for overall mortality at 3 and 12 months among patients diagnosed with PE by CTPA.     

Effect of slice thickness on liver lesion detection and characterisation by multidetector CT

The purpose of our study was to compare the effectiveness of 3.2 mm, 5 mm and 7.5 mm slice thicknesses in the detection and characterisation of liver lesions found on CT in patients with known or suspected malignant disease. 110 patients underwent portal phase imaging using four-slice MDCT. Two blinded observers independently read hard copy images at each slice thickness. The size and location of each lesion detected was recorded by each observer on a diagram of liver segmental anatomy. Each lesion was characterised as benign, malignant or indeterminate in nature. A diagnostic confidence score was allocated for each lesion on a scale of 1–4. The pathology or behaviour of lesions was assessed using surgery with intra-operative ultrasound (IOUS) and histology, or interval imaging with MRI, CT, or sonography. 294 lesions were detected, 64 (22%) of which were malignant. Both observers detected significantly more lesions on the 3.2 mm versus 7.5 mm slice thickness (p < 0.0001). Both observers detected more malignant lesions on 3.2 mm and 5 mm slice thicknesses versus 7.5 mm. As slice thickness decreased there was a significant increase in the sensitivity of malignant lesion detection for observer 1 (p < 0.001) and borderline significance for observer 2 (p = 0.07). As slice thickness decreased the proportion of lesions characterised as indeterminate by both observers fell. With thinner slices, both detection and characterisation of liver lesions were improved. A slice thickness no greater than 5 mm should be used to maximise both detection and correct characterisation of liver lesions.     

急性CO中毒患者激素干预对血清TNF-α,IL-8水平的影响

1 临床资料选择2002-11/2003-04急性CO中毒患者60(男37,女23)例,年龄15～78(平均40)岁. 常规治疗组给予常压高流量鼻导管吸氧,每日高压氧治疗1次(2ATA下经活瓣式面罩吸入纯氧1 h),脱水减轻脑水肿、改善脑代谢、促进脑细胞功能恢复等治疗;干预治疗组在常规治疗的基础上,地塞米松10 mg iv, 2次/d,分别于病例确诊后即刻(中毒后2 h以内)、12,24和48 h抽取肘静脉血3 mL,采用放免法(试剂盒由北京东亚免疫技术研究所提供),严格按说明书操作检测血清检测TNF-α,IL-8.     

P-selectin glycoprotein ligand-1 is broadly expressed in cells of myeloid, lymphoid, and dendritic lineage and in some nonhematopoietic cells

P-selectin glycoprotein ligand-1 (PSGL-1) is a muclin-like glycoportein ligand for P- and E-selectin on myeloid cells and a subset of lymphocytes. We used flow cytometry and immunohistochemistry to examine expression of PSGL-1 on minor leukocyte populations, differentiating hematopoletic cells, and nonhematopoietic tissues using two monoclonal antibodies to distinct protein epitopes on PSGL-1. In the bone marrow, PSGL-1 was expressed on myeloid cells from the myeloblast stage to the segmented neutrophil, but was not detected on erythroblasts or megakaryocytes. All types of circulating myeloid cells expressed PSGL- 1, and PSGL-1 was retained after extravasation of myetoid cells into tissues. PSGL-1 was also expressed on circulating dendritic cells, monocyte-derived dendritic cells, dendritic cells in lymphoid tissues and epidermis, and follicular dendritic cells. All types of lymphoid cells examined expressed PSGK-1, including immature and mature thymocytes, naive and memory T cells, gamma/delta T cells, netural killer cells, B cells and CD34+ progenitor cells. However, PSGL-1 levels were substantially lower on tonsillar lymphocytes than on circulating lymphocytes, suggesting that PSGL-1 expression is down regulated during or after entry of lymphocytes into secondary lymphoid tissue. Although PSGL-1 antigen was detected primarily on hamatopoietic cells, it was also present on time epithelium of the fallopian tube. Furthermore, PSGL-1 antigen gen was detected sporadically on microvascular endothelium in some pathologic tissues. This suggests that PSGL-1 may have functions other than mediating leukocyte adhersion.     

Treatment of acute nonlymphocytic leukemia: use of anthracycline- cytosine arabinoside induction therapy and comparison of two maintenance regimens

Patients with acute nonlymphocytic leukemia were given remission induction therapy consisting of cytosine arabinoside and an anthracycline. Those patients who experienced complete remission received two courses of consolidation therapy and were randomized to receive maintenance therapy consisting of either daily chemotherapy with reinforcements every 3 mo or reinforcement therapy only every 6 wk. The overall complete remission rate was 66%, with 80% complete remission for previously untreated patients less than 60 yr of age who did not have a prior history of malignancy. Remission durations were the same for patients treated with both maintenance regimens. The major determinant for successful remission induction therapy was patient age, with older patients frequently succumbing to intercurrent infection. Documented leukemic cell resistance to the therapy employed was only rarely encountered. Once remission was achieved, age was no longer a determinant of patient survival, since duration of remission was independent of age. Remission durations were directly related to leukemic cell retention of cytosine arabinoside triphosphate. Hence therapy for acute nonlymphocytic leukemia can be divided into two separate areas: remission induction and remission maintenance.     

Immunoglobulin gene rearrangements in remission bone marrow specimens from patients with acute lymphoblastic leukemia

Recombinant DNA probes for the joining (JH) segment of the immunoglobulin heavy chain gene were used to detect molecular rearrangements of this gene in the DNA of bone marrow cells obtained during remission of acute lymphoblastic leukemia (ALL). This molecular approach was optimized and found to exceed the sensitivity of conventional morphologic screening for detecting residual leukemia cells; one leukemic cell in 500 normal nucleated bone marrow cells was easily detected using this approach. In the present study, bone marrow from three of seven patients in complete clinical remission (defined morphologically) contained leukemic cells in these proportions. This analysis may be of use in evaluating the status of clinical remission in selected ALL patients.     

Topoisomerase II levels and drug sensitivity in adult acute myelogenous leukemia

The topoisomerase (topo) II-directed agents etoposide, daunorubicin (DNR), and amsacrine (m-AMSA) are widely used in the treatment of acute myelogenous leukemia (AML). In the present study, multiple aspects of topo II-mediated drug action were examined in marrows from adult AML patients. Colony-forming assays revealed that the dose of etoposide, DNR, or m-AMSA required to diminish leukemic colony formation by 90% (LD90) varied over a greater than 20-fold range between different pretreatment marrows. Measurement of nuclear DNR accumulation in the absence and presence of quinidine revealed evidence of P-glycoprotein (Pgp) function in 8 of 82 samples at diagnosis and 5 of 36 samples at first relapse, but the largest quinidine-induced increment in DNR accumulation (< 2-fold) was too small to explain the variations in drug sensitivity. Restriction enzyme-based assays and sequencing of partial topo II alpha and topo II beta cDNAs from the most highly resistant specimens failed to demonstrate topo II gene mutations that could account for resistance. Western blotting of marrow samples containing greater than 80% blasts revealed that the content of the two topo II isoenzymes varied over a greater than 20-fold range, but did not correlate with drug sensitivity in vitro or in vivo. In addition, levels of topo II alpha and topo II beta in 46 of 47 clinical samples were lower than in human AML cell lines. Immunoperoxidase staining showed that these low topo II levels were accompanied by marked cell-to- cell heterogeneity, with topo II alpha being abundant in some blasts and diminished or absent from others. There was a trend toward increasing percentages of topo II alpha-positive cells in pretreatment marrows that contained more S-phase cells. Consistent with this observation, treatment of patients with granulocyte-macrophage colony- stimulating factor for 3 days before chemotherapy resulted in increases in topo II alpha-positive cells concomitant with increases in the number of cells traversing the cell cycle. These observations have implications for the regulation of topo II in AML, for the use of topo II-directed chemotherapy, and for future attempts to relate drug sensitivity to topo II levels in clinical material.     

Treatment of acute graft-versus-host disease with humanized anti-Tac: an antibody that binds to the interleukin-2 receptor

Humanized anti-Tac is a genetically engineered human IgG1 monoclonal antibody specific for Tac, the alpha subunit of the interleukin-2 (IL- 2) receptor, and blocks IL-2-dependent activation of human T lymphocytes. The safety, pharmacokinetics, and immunosuppressive activity of humanized anti-Tac were evaluated in 20 patients who developed acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. Patients had developed acute GVHD at 5 to 26 (median, 14) days after transplantation and had failed to respond to primary therapy with glucocorticoids. Sequential groups of 4 patients each received a single 1-hour infusion of antibody in escalating doses of 0.5, 1.0, or 1.5 mg/kg; 8 additional patients were then treated with 1.5 mg/kg. A second infusion of antibody was administered after 11 to 48 (median, 16) days in 8 patients who had transient improvement of GVHD after the first infusion. Acute side effects, limited to chills in 1 patient and diaphoresis in another, were observed during or shortly after the antibody infusion. Overall improvement of acute GVHD occurred in 8 patients, 6 of whom were treated with a single antibody infusion and 2 with two infusions. Four responses were complete and 4 were partial. Three additional patients had improvement in one organ but progression in another. Responses occurred in 9 of 16 cases with skin disease, 3 of 15 with liver disease, and 6 of 12 with gastrointestinal disease. Two patients survive at 529 and 645 days after antibody treatment. Two patients died after relapse of leukemia. Sixteen patients died of infection or organ failure between 5 and 211 (median, 55) days. The terminal elimination half-life of the antibody was 44 to 363 hours, with a harmonic mean of 79, 88, and 94 hours, respectively, for the three doses studied. Absolute peripheral blood T-lymphocyte counts remained unchanged during the 56 days after infusion of the antibody. A fraction of circulating T cells expressed the alpha chain of the IL-2 receptor that, in some patients, was bound by antibody in vivo up to 28 days after treatment. No patient developed a measurable antibody response to humanized anti-Tac. Humanized anti-Tac has a long half-life after intravenous injection in humans, superior to any rodent monoclonal antibody specific for human T cells, and does not appear to induce antibody formation in recipients of marrow transplants. Improvement of steroid-refractory GVHD in 40% of patients after only one or two antibody infusions indicates that humanized anti-Tac is immunosuppressive.