Outcome for patients who relapse after allogeneic bone marrow transplantation for chronic myeloid leukemia. Chronic Leukemia Working Party. European Bone Marrow Transplantation Group

We studied the clinical course of 130 chronic myeloid leukemia (CML) patients (89 males and 41 females) in the European Bone Marrow Transplantation Group (EBMT) registry who received transplants before January 1, 1988 and who subsequently had evidence of recurrent leukemia. All patients had received a pretransplant conditioning regimen including total body irradiation (TBI). The first evidence of relapse was cytogenetic only in 74 (57%) patients and hematologic in 56 (43%). The overall actuarial survival from relapse was 36% at 6 years, with a significantly higher proportion of survivors among female patients (53% v 30%; P < .002). In univariate analysis, the 6-year probability of survival was 52% for patients with cytogenetic relapse and 30% for patients relapsing in chronic phase (CP), while no patient who relapsed in advanced phase (AP or BC) survived more than 3.5 years from relapse (P < .0001). The actuarial survival of patients relapsing before 6 months, between 6 and 12 months, and later than 12 months after transplant was 27%, 26%, and 45%, respectively (P < .002). Among patients with cytogenetic relapse, partial or complete disappearance of Ph-positive cells occurred in 40% of untreated patients and in 42% of those treated with interferon (IFN). However, IFN therapy significantly delayed progression toward hematologic disease. Cytogenetic responses were observed in 25% of patients who received IFN for relapse into CP, while only one minor cytogenetic response was reported in patients on conventional chemotherapy. For patients presenting with cytogenetic relapse as well as for those in hematologic relapse, IFN therapy significantly improved the 2-year probability of survival. However, long-term survival for IFN-treated patients in either group was not different from long-term survival in comparable patients not receiving IFN therapy. Twenty-nine patients of this series underwent a second bone marrow transplant (BMT) and the projected survival at 4 years after the second transplant is 28%. In multivariate Cox regression analysis, four factors remained significantly associated with survival: disease phase at relapse (P < .0001), duration of time interval from BMT to relapse (P = .0001), interferon therapy at relapse (P = .0024), and patient sex (P = .0032). This retrospective study provides evidence that some patients who relapse after BMT may benefit from treatment with IFN; a second BMT may offer the chance of cure. Data from this analysis may be useful in designing future prospective trials on posttransplant CML relapse.     

Bcl-x rather than Bcl-2 mediates CD40-dependent centrocyte survival in the germinal center

Both rapid B-cell proliferation and programmed cell death (PCD) occur during the differentiation and selection of B cells within the germinal center. To help elucidate the role of Bcl-x in B-cell antigen selection and PCD within the germinal center, we examined its expression in defined B-cell populations and by immunochemistry of tonsil tissue. Purified B-cell fractions enriched for centrocytes express high amounts of Bcl-x and relatively low amounts of Bcl-2, whereas fractions enriched for centroblasts lack significant levels of both proteins. Consistent with this observation, immunocytochemistry localized Bcl-x within cells scattered throughout the germinal center. Stimulation of tonsil B cells with either CD40 or Staphylococcus aureus Cowan increase bcl-x mRNA and protein levels. Treatment of a cell line with a germinal center phenotype (RAMOS) or the tonsillar B-cell centroblast fraction with CD40 rapidly increased Bcl-x levels and partially rescued B cells from PCD. These data suggest that Bcl-x rather than Bcl-2 may rescue centrocytes during selection in the germinal center.     

Collagen-induced arthritis in rhesus monkeys: evaluation of markers for inflammation and joint degradation

The objective of this study was to analyse parameters in rhesus monkey collagen-induced arthritis (CIA) with which the inflammation and destruction of the joints can be described in quantitative terms. CIA was induced in genetically susceptible and resistant monkeys, which can be distinguished on the basis of the dominant resistance marker Mamu- A26. The disease course was monitored daily using a semiquantitative scoring system. Plasma samples were collected once or twice weekly and analysed for C-reactive protein (CRP). Urines were collected overnight once a week and analysed for excretion rates of the collagen cross- links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP). The results show that periods of active CIA are characterized by substantial weight loss and increased plasma CRP levels, followed shortly thereafter by increased excretion rates of the collagen cross- links HP and LP. Remission of the disease can be recognized by a decline in plasma CRP levels and especially an increase in body weight. The highest CRP levels were found in the most severely arthritic monkeys, indicating a possible relationship of the absolute plasma CRP levels to the severity of inflammation. During periods of active arthritis, increased excretion rates of collagen cross-links HP and LP in the urine were found. In particular, the major collagen cross-link in articular cartilage, HP, showed a strong increase (9- to 15-fold). The excretion rates of LP, which is considered as a bone-specific degradation marker, only increased 4- to 6-fold, thus indicating predominant destruction of cartilage and less of bone. In conclusion, the severity of CIA can be monitored in a quantitative manner using plasma CRP levels, urinary excretion rates of HP and LP, and body weights, superimposed on semiquantitative clinical scores. The parameters also facilitate a more objective assessment of the effect of anti-arthritic drugs in the model than with the clinical scores alone.      

Maintenance of murine long-term repopulating stem cells in ex vivo culture is affected by modulation of transforming growth factor-beta but not macrophage inflammatory protein-1 alpha activities

Transforming growth factor-beta (TGF-beta) and macrophage inflammatory protein-l alpha (MIP-1 alpha) are both well-described inhibitors of committed and multipotential hematopoietic progenitors. The effect of these cytokines; on true stem cell activity in ex vivo culture systems as assayed by murine long-term repopulating activity (LTRA) has not been examined. We studied the stem cell effects of the addition of these cytokines to ex vivo cultures containing interleukin-3 (IL-3), IL- 6, and stem cell factor (SCF), using the murine competitive repopulation assay. We also tested the impact of adding an anti-TGF- beta neutralizing antibody, to ask whether abrogation of autocrine/paracrine TGF-beta may protect or enhance the survival of LTRA during ex vivo culture. TGF-beta 1 had significant suppressive effects on both short- and long-term repopulating activities, and anti- TGF-beta antibody had enhancing effects compared with control cultures containing IL-3, IL-6, and SCF alone. MIP-1 alpha had no significant effects on either short- or long-term repopulating ability. These data suggest that abrogation of TGF-beta during suspension culture may allow enhanced survival or even expansion of primitive cells ex vivo, with implications for many applications, including gene therapy.     

某综合医院医院感染现况调查与分析

目的：调查并分析医院感染的发生情况,指导医院感染预防与控制工作。方法：对2011年11月10日所有住院患者采用床旁调查表和病历查阅相结合的方法进行现况调查分析。结果：2006例患者中,医院感染48例,医院感染现患率2．39％,例次感染率2．54％,感染率最高科室是ICU;感染部位主要是下呼吸道;培养出病原菌14株;抗菌药物使用率是40．13％,使用率最高的科室是ICU和儿科。结论：对感染率较高科室进行重点监测及干预,预防和控制医院感染的暴发。     

打造“公建民营多元化服务”的老年康复医院

目前,我国面临着前所未有的人口老龄化的严峻挑战。仅拿杭州市为例,预计到2015年60岁以上的老年人口达148万,约占总人口的20%,高龄老人将达23万,约占老年人口的16%左右。在如此庞大的老年群体中,他们的养护、医疗、康复等需求难以满足。因此,"医养结合"型老年康复医院的建设与发展,将是今后卫生事业发展的重大课题。     

声脉冲辐射力成像技术对子宫腺肌病的诊断价值

目的观察子宫腺肌病（AM）患者月经周期中病变肌层声触诊组织量化VTQ值变化规律与特点,探讨应用声脉冲辐射力成像（ARFI）技术提高该病早期诊断率的可行性。方法应用超声声脉冲辐射力成像（ARFI）模式声触诊组织量化（VTQ）功能分别于月经周期的卵泡早期和黄体中期观测子宫腺肌病患者病变肌层声触诊组织量化VTQ值,分析对比观察组2个时期间及两组相应时期间VTQ值。结果黄体中期病变肌层VTQ值高于卵泡早期VTQ值,且差异有统计学意义（P〈0．05）。结论超声声脉冲辐射力成像（ARFI）技术能实时、敏感检测子宫腺肌病VTQ值,而且可重复性好．同时能体现子宫腺肌病肌层病变随月经周期性改变,有望成为子宫腺肌病诊断手段之一,从而为提高该病的早期诊断率提供有效依据。     

伽玛刀联合紫杉醇/卡铂同步加巩固治疗局部晚期非小细胞肺癌临床观察

目的观察体部伽玛刀联合紫杉醇/卡铂同步加巩固治疗局部晚期非小细胞肺癌的临床疗效及毒副反应。方法将62例局部晚期非小细胞肺癌患者随机分为A(30例)、B(32例)两组;均给予伽玛刀同步联合紫杉醇/卡铂方案化疗(紫杉醇45 mg/m2+卡铂AUC=2,第1天,1次/周,共6次);B组在与A组相同治疗后,再给予巩固化疗(紫杉醇175 mg/m2+卡铂AUC=5,第1天,1次/3周,共2周期)。比较临床疗效和毒副反应。结果近期有效率(CR+PR):A组76.67%,B组81.25%;1、2年生存率及中位生存期:A组分别为63.33%、30.00%和14.6个月,B组分别为68.75%、37.50%和16.9个月;两组比较,无统计学差异(P>0.05);毒副反应:B组明显高于A组。结论体部伽玛刀联合紫杉醇/卡铂同步治疗局部晚期非小细胞肺癌安全、有效,而在此基础上加予巩固化疗未能明显提高此类患者的生存率。