High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Identification of glycoprotein Ib as a target for autoantibody in idiopathic (autoimmune) thrombocytopenic purpura

An antibody (DIL) from a patient with idiopathic thrombocytopenic purpura (ITP) was shown to have autospecificity on the basis of reactions with autologous platelets that were identical to those obtained with platelets from normal subjects. DIL antibody also reacted strongly in an immunofluorescence test with platelets from a patient with Glanzmann's thrombasthenia, but failed to react with platelets from a patient with the Bernard-Soulier syndrome who was known to be deficient in glycoprotein Ib (GPIb). Purified GPIb and control platelets, but not Bernard-Soulier platelets, inhibited the lytic activity of DIL. Using the GPIb-specific monoclonal antibody AP1 and one-dimensional rocket electrophoresis into gels containing rabbit antihuman platelet membrane antibody, it was shown that staphylococcal protein A-Sepharose beads coated with DIL antibody selectively remove GPIb from solubilized platelet preparations. By crossed immunoelectrophoresis it was found that DIL recognizes a determinant on GPIb on the membrane side of the cleavage site of the platelet calcium- activated protease (calpain). These studies provide direct evidence for binding of a platelet autoantibody to a determinant on GPIb relatively close to the site of insertion of this protein into the platelet membrane.     

Recovery phase of acute experimental autoimmune encephalomyelitis in rats corresponds to development of endothelial cell unresponsiveness to interferon gamma activation

Activation of the vascular endothelium is important in the development of inflammation. Activated endothelial cells (EC) express surface markers not expressed by quiescent EC. These surface markers augment adhesion reactions and leukocyte migration. We examined microvessel EC activation longitudinally in experimental autoimmune encephalomyelitis (EAE) in Lewis rats. CNS microvessels were isolated at 0, 3, 7, 12, 20, and 30 days post-inoculation (PI). Normal and CFA-injected rat microvessels do not express activation antigens (Ag). Increased expression of major histocompatibility complex (MHC) class II molecule and intercellular adhesion molecule-1 (ICAM-1) were detected on CNS microvessels from immunized rats at 7 days PI, prior to development of clinical signs, and at 12 days PI. Enhanced MHC class I molecule was seen only at 12 days. MHC class II molecule expression was focally expressed along microvessel fragments. By 20 days PI, EC did not exhibit increased levels of any of the markers tested. Perivascular cells (possibly pericytes), however, were found to express MHC class II molecule and ICAM-1 up to 30 days PI. During the recovery phase isolated CNS microvessels from MBP-immunized rats were unresponsive to IFNγ-mediated endothelial activation. Unresponsiveness was independent of IFNγ concentration. These results suggest that the endothelium is restored to functional quiescence during the recovery phase of acute EAE. © 1996 Wiley-Liss, Inc.     

Radiotherapy for melanotic freckles

Five patients who received radiotherapy (RT) for 7 melanotic freckles (MF, also known as Hutchinson's freckles, lentigo maligna) were reviewed 8 to 37 months after their treatment by RT. Local control and a favourable cosmetic result occurred in all patients. Treatment toxicity was minimal. Few reports about the use of RT for MF exist. Many other treatments including observation alone have been associated with high rates of recurrence, and in some cases conversion to invasive melanoma has occurred. RT appears to be a safe and effective treatment for this condition, providing that doses equivalent to 44 Gy in 11 fractions or more are given.     

灰黄霉素中灰黄霉酸杂质及色泽的考查

目的：本文采用薄层色谱法考查了不同厂家灰黄霉素中灰黄霉酸杂质的存在。方法；以丙酮为溶媒，精制灰黄霉素，摸索分离条件，探讨杂质限度，考查产品色泽。结果：杂质均值为０．２７６％，ＲＳＤ为０．１６８％。结论：对改进产品检验方法，提高产品质量具有一定的参考价值。