Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: a randomized trial of busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen: a report from the French Society of Bone Marrow Graft (SFGM)

From March 1988 to March 1991, 19 French bone marrow transplant (BMT) centers participated in a prospective randomized trial comparing two conditioning regimens for patients with chronic myeloid leukemia transplanted in first chronic phase with an HLA identical sibling donor. A total of 120 consecutive patients were randomized to receive either 120 mg/kg of cyclophosphamide followed by total body irradiation (CY-TBI; n = 55) or 16 mg/kg of busulfan followed by 120 mg/kg of CY (BU-CY; n = 65). Two different TBI regimens were used. Thirteen patients received a 10-Gy single-dose TBI (SDTBI), and 42 received a fractionated TBI (FTBI). Median time between diagnosis and BMT was 315 days. Overall 5-year actuarial survival was 62.9% (65.8% +/- 12.5% for CY-TBI and 60.6 +/- 11.7% for BU-CY; P = .5), and overall disease-free survival was 55% (51% +/- 14% for CY-TBI and 59.1% +/- 11.8% for BU-CY; P = .75). All patients conditioned with CY-TBI experienced sustained engraftment; in contrast, 4 of 65 patients conditioned with BU-CY rejected the graft (P = .18). There was no significant statistical difference between the two groups regarding transplant-related mortality (29% for CY-TBI and 38% for BU-CY; P = .44). So far, with a median follow up of 42 months, 11 patients have relapsed; 9 relapses occurred after CY-TBI, mostly after FTBI (8 of 9) and 2 after BU-CY (P = .02). The actuarial risk of relapse was 4.4% +/- 6.7% after BU-CY, 11.1% +/- 20.8% after SDTBI, and 31.3% +/- 18.1% after FTBI (P = .039). In addition, independently of the conditioning regimen, the increase of posttransplant immunosuppression in 16 patients with an anti- interleukin-2 receptor monoclonal antibody (MoAb) in addition to a short course of methotrexate and cyclosporine was shown to increase the actuarial risk of relapse (57% +/- 30% with MoAb v 9% +/- 7.3% without MoAb; P = .001). We conclude that BU is an acceptable alternative to TBI for patients with chronic myeloid leukemia in first chronic phase receiving BMT from HLA identical sibling donors. Both BU-CY and CY-TBI regimens gave similar transplant-related mortality, and the antileukemic efficiency of BU-CY regimen was either similar or even higher than that of CY-TBI.     

Role of extracellular adenosine triphosphate in the cytotoxic T- lymphocyte-mediated lysis of antigen presenting cells

The lysis of antigen presenting cells (APCs) by cytotoxic T lymphocytes (CTLs) may be one mechanism whereby an immune response is downregulated by Staphylococcus superantigens. Disappearance of monocytes/macrophages from staphylococcal enterotoxin A (SEA)-activated peripheral blood mononuclear cell (PBMC) cultures, but not from control PBMC cultures was seen by flow cytometry. Recently, adenosine triphosphate (ATP) has been described as an effector molecule in CTL-mediated lysis of some murine tumor target cells. We have also shown that ATP caused the lysis of human macrophages, and that treatment of cells with interferon gamma (IFN gamma) rendered macrophages significantly more sensitive to ATP than untreated cells. To show that this purine nucleotide may play a role in modulating the immune system, we generated human CTLs that were stimulated with SEA, and used them as effector cells against SEA-pulsed autologous macrophages. CTLs were found to specifically lyse SEA-pulsed macrophages, while control, unpulsed, macrophages were unaffected. The addition of hexokinase, an enzyme that hydrolyzes ATP, significantly abrogated the killing of SEA-pulsed cells during the assay. In examining the mechanism of cytotoxicity, electron microscopy showed that macrophages incubated with both ATP and CTLs underwent necrosis, rather than apoptosis. From these results, it is suggested that ATP is released from CTLs during antigen presentation, and that IFN gamma- activated macrophages, which are inherently more sensitive to this mediator, are readily lysed and therefore removed from circulation, thus downregulating an immune response.     

Detection of serum TNF-α,IFN-γ,IL-6 and IL-8 in patients with hepatitis B

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Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure

Fifteen elderly patients with normal left ventricular (LV) systolic function and New York Heart Association functional class II-III were studied. The effect of verapamil on LV diastolic function was assessed by congestive heart failure (CHF) score, treadmill exercise test, and Doppler echocardiography at baseline, and after each three-month treatment period (placebo or verapamil 120 mg once daily), separated by a one-week washout period before crossover. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. Verapamil treatment significantly improved CHF score at 3 months (3.5 +/- 0.5, p<0.05) compared with baseline (5.6 +/- 0.5) or placebo (5.5 +/- 0.5). The exercise time was similar at baseline (7.4 +/- 1.2 min) and after placebo (7.4 +/- 1.3 min) treatment but significantly (p<0.05) increased after verapamil (8.3 +/- 1.2 min) treatment. The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil (1.11 +/- 0.08) treatment compared with placebo (0.91 +/- 0.07, p<0.05) and baseline (0.89 +/- 0.08) which had similar durations. The isovolumic relaxation time was significantly (p<0.05) decreased from 84 +/- 12 ms at baseline and 86 +/- 13 ms with placebo to 73 +/- 9 ms with verapamil. The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF, three months treatment with verapamil can improve CHF, increase exercise tolerance and improve LV diastolic function.     

In vitro evaluation of a calcium phosphate cement root canal filler/sealer

An in vitro dye leakage study was performed to compare the apical leakage of a fill with injectable calcium phosphate cement (CPC) filler/sealer and a master silver cone with leakage from a fill of Sealapex sealer and laterally condensed gutta-percha. Ten instrumented, extracted, single-rooted human teeth were obturated with either laterally condensed gutta-percha and Sealapex as the sealer or with a single master cone and the CPC paste sealer. Additional teeth were included in the study to serve as controls. The teeth were placed in 1% poly-R dye solution (pH 7.0) for 5 days. After the teeth were longitudinally sectioned apical leakage of dye was measured. There were no significant differences between the CPC and Sealapex groups. The single cone CPC procedure provided an adequate apical seal against dye penetration. Should retreatment become necessary the single cone may be removed to provide access for instrumentation.     

Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor

Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL- 10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.     

综合干预措施控制人群肠道传染病的效果

张家港市位于苏南水网地区,全市85余万人口,面积998 km2,人口密度高达860人·km-2.全市工商经济和服务行业发达,外来流动人口达6000人·d-1,外来常住人口达10万人·a-1,而且本地人口流动量大,经对该市塘桥镇8000人调查,30%以上人口每天至少有一次不在家内用餐.农村人口以前普遍饮用河塘水及浅井水,其中饮用4 m～6 m深的井水者近40万人.     

药物诱导细胞凋亡治疗肝癌

细胞凋亡(apoptosis)是细胞自然衰老、死亡的一种形式,是一切生物正常胚胎发生过程和人类发育过程细胞清除的正常途径。这一过程的紊乱,将导致人类发生多种疾病。许多研究资料表明,肿瘤的发生与细胞凋亡有密切关系,细胞凋亡异常在肿瘤发生和发展过程中具有非常重要的病理生理意义,细胞凋亡参与肿瘤的起始过程,并对癌症的发生起负相调控作用,Dive认为肿瘤的化疗、放疗的目的就是诱导肿瘤细胞凋亡。因此,在肝癌的治疗中不断地探讨新方法新途径,包括化疗药物、放射线、细胞因子、激素和基因编码等。近年来大量实验研究发现,肝癌细胞可以通过人为地触发细胞凋亡而被清除。其中药物诱导细胞凋亡对今后肝癌治疗研究提供了诱人的前景。不同种类的化学药物,生物药物和中药对不同种类肿瘤敏感细胞有促进凋亡作用。部分化疗药物、生物药在体外实验中能诱导肝癌细胞凋亡,如顺铂、环磷酰胺、阿霉素、细胞因子等。下面就药物诱导细胞凋亡治疗肝癌研究简要综述如下。