Results of a Double Blind Placebo Controlled Study of Ondansetron as an Antiemetic During Total Body Irradiation in Patients Undergoing Bone Marrow Transplantation

Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.     

年龄对大鼠肝脏生物转化功能及膜流动性的影响

通过与青年(3～4月)及中年(14月)组比较,研究了老年(24月)大鼠肝脏生物转化酶活性改变及膜流动性变化。结果表明,老年大鼠肝微粒体P-450含量、NADPH-细胞色素C还原酶活性无明显改变,但氨基比林N-脱甲基酶、苯胺羟化酶活性明显降低,且微粒体及胞浆GST、胞浆GSH-Px活性也明显下降;同时肝微粒体膜脂区流动性明显降低,膜Ch/PL值显著增大。研究提示,微粒体膜脂质环境及流动性变化与上述生物转化功能改变可能有一定的联系。     

苯巴比妥诱导下大鼠肝微粒体药酶活性与膜流动性变化的相关性

本文用ANS和DPH为荧光探剂,研究苯巴比妥(PB)诱导下大鼠肝微粒体膜脂区流动性与膜药酶活性变化的相关性。结果表明,经PB诱导后在增加肝微粒体蛋白质含量,P-450含量及NADPH-细胞色素C还原酶等酶活性的同时,肝微粒体膜流动性明显增大,且膜深层流动性的增大与膜氨基比林N-脱甲基酶、细胞色素C还原酶活性增加有明显的直线正相关。膜胆固醇/碑脂比值明显降低。此结果提示,肝微粒体膜流动性的适当增大与PB增加单胺氧化酶系统活性之间可能存在着某种联系。     

灵芝多糖对混合淋巴细胞培养反应中白细胞介素2生成和T细胞亚类的影响(英文)

利用混合淋巴细胞培养反应研究了灵芝多糖的免疫作用机理。结果表明培养12h,灵芝多糖(25,50,100,200μg/ml)可促进白细胞介素2的分泌,且具有剂量依赖关系。培养4d后,可增加总的细胞回收量以及Lyt 2~+和L3T4~+细胞的回收量。灵芝多糖还明显增强细胞毒T细胞的功能,在浓度为200μg/ml时,其杀伤活性增加100％。     

Cells expressing human glucocerebrosidase from a retroviral vector repopulate macrophages and central nervous system microglia after murine bone marrow transplantation

Gaucher disease is an inherited lysosomal storage disease in which the loss in functional activity of glucocerebrosidase (GC) results in the storage of its lipid substrate in cells of the macrophage lineage. A gene therapy approach involving retroviral transduction of autologous bone marrow (BM) followed by transplantation has been recently approved for clinical trial. Amelioration of the disease symptoms may depend on the replacement of diseased macrophages with incoming cells expressing human GC; however, the processes of donor cell engraftment and vector gene expression have not been addressed at the cellular level in relevant tissues. Therefore, we undertook a comprehensive immunohistologic study of macrophage and microglia replacement after murine BM transplantation with retrovirus-marked BM. Serial quantitative PCR analyses were employed to provide an overview of the time course of engraftment of vector-marked cells in a panel of tissues. Following reconstitution of hematopoietic tissues with vector- marked donor cells at early stages, GC+ cells began to infiltrate the liver, lung, brain, and spinal cord by 3 months after transplant. Immunohistochemical analyses of PCR+ tissues using the 8E4 monoclonal antibody specific for human GC revealed that macrophages expressing human GC had partially reconstituted the Mac-1+ population in all tissues in a manner characteristic to each tissue type. In the brain, 20% of the total microglia had been replaced with donor cells expressing GC by 3 to 4 months after transplant. The finding that significant numbers of donor cells expressing a retroviral gene product immigrate to the central nervous system suggests that gene therapy for neuronopathic forms of lysosomal storage diseases as well as antiviral gene therapy for AIDS may be feasible.     

Acute Myeloid Leukaemia Following Matched Allogeneic Bone Marrow Transplantation for T-Cell Lymphoblastic Lymphoma

It is now commonly acknowledged that cells from some acute leukaemias may bear both myeloid and lymphoid markers at diagnosis, or that relapse following initial treatment may occur, with blast cells phenotypically different from those seen at initial diagnosis. Patients showing evidence of bi-linear disease seem to carry a worse prognosis for cure. Here, a case of T-cell lymphoblastic lymphoma is reported, who relapsed with acute myeloblastic leukaemia, following allogeneic bone marrow transplantation.

Early diagnosis of disease with lymphoid and myeloid features is therefore warranted, so that intensive treatment programmes may be offered, in anticipation of permanent cure.     

Collection of peripheral blood progenitor cells after the administration of cyclophosphamide, etoposide, and granulocyte-colony- stimulating factor: an analysis of 497 patients

BACKGROUND: There is great interpatient variability in the number of peripheral blood stem cells collected, as measured by CD34+ cell content, after the administration of chemotherapy and a growth factor. The ability to predict patients who fail to yield adequate quantities of CD34+ cells would be of value. However, very few reports include large numbers of patients treated in an identical fashion. STUDY DESIGN AND METHODS: Between 1991 and 1995, 497 consecutive patients with a variety of malignant diseases received cyclophosphamide (4 g/m2), etoposide (600 mg/m2), and granulocyte-colony-stimulating factor (6 micrograms/kg/day) for mobilization and collection of a target dose > or = 2.5 × 10(8) CD34+ cells per kg. Multivariate analyses were performed to determine the factors associated with failure to achieve this target harvest. RESULTS: A median of 14.71 × 10(6) CD34+ cells per kg (range, 0.08-137.55) was harvested with a median of 2 (range, 1–11) apheresis procedures. Ninety-one percent of patients yielded > or = 2.5 × 10(5) CD34+ cells per kg. Patients with Stage II-III breast cancer, who had pretreatment platelet counts > or = 150 × 10(9) per L and patients who underwent < or = 1 prior chemotherapy regimen had improved CD34+ cell yields. However, most patients with adverse risk factors yielded > or = 2.5 × 10(6) CD34+ cells per kg. CONCLUSION: A regimen of cyclophosphamide, etoposide, and granulocyte-colony-stimulating factor led to the successful collection of adequate numbers of CD34+ cells in most patients without excessive toxicity. These observations confirm previous reports that intense prior therapy adversely affects the quantity of CD34+ cells harvested. Pretreatment and posttreatment variables did not predict with any certainty the small fraction of patients who fail to yield > or = 2.5 × 10(6) CD34+ cells per kg via multiple apheresis procedures.