Platelet refractoriness and alloimmunization in pediatric oncology and bone marrow transplant patients

BACKGROUND: The purposes of this study were to determine the overall incidence of platelet refractoriness and alloimmunization among multiply transfused children on a medical oncology and bone marrow transplant service and to evaluate the effect of routine white cell reduction in blood components on that incidence. STUDY DESIGN AND METHODS : The platelet transfusion records of 128 consecutive children admitted to the hospital and requiring blood component support for the treatment of disease were evaluated retrospectively. Mean corrected count increments (CCIs) for each patient were calculated for all random- donor platelet transfusions given within 7 days of the routine weekly testings of the patient's serum for lymphocytotoxic antibodies (LCTAbs). Mean CCIs for HLA-matched platelet transfusions were calculated separately for the patients receiving them. RESULTS : Thirty- one patients (24%) had or developed persistently positive LCTAbs (patient's serum reacted with > or = 3/10 panel lymphocytes); 22 (71%) of these patients had a mean CCI < 7.5 to random-donor platelet transfusions. In contrast, of the 97 patients with negative or transiently positive LCTAbs, only 25 (26%) had a mean CCI < 7.5. The overall incidence of platelet refractoriness (CCI < 7.5) was 37 percent. Patients with acute myelogenous leukemia had a significantly (p < 0.01) reduced incidence (17%) of low CCIs, with or without positive LCTAbs, as compared to patients with other malignant or nonmalignant disorders (41%). No difference in the incidence of LCTAbs or low CCIs was seen in patients undergoing allogeneic or autologous bone marrow transplant or receiving drug therapy only. Among the 24 patients who received HLA-matched platelets, only those with positive LCTAbs showed a significant improvement in CCIs over that achieved with random-donor platelet transfusions. Routine white cell reduction in red cell and platelet components with third-generation white cell filters was performed prior to transfusion in 73 of the patients. There was no significant difference between the incidence of LCTAbs and/or low CCIs in this group and that in the 55 children receiving unfiltered transfusions. CONCLUSION : Alloimmunization and platelet refractoriness occur in pediatric oncology and bone marrow transplant patients, but the incidence-particularly in children with acute myelogenous leukemia- -appears to be low. The detection of LCTAbs predicts a poor response to random-donor platelet transfusion, but most such patients show improved CCIs with HLA-matched platelets. Routine use of white cell-reduction filters has thus far failed to eliminate alloimmunization in children requiring prolonged blood component support.     

Plateletpheresis in the management of thrombocytosis

Acute thrombotic and hemorrhagic manifestations of thrombocytosis associated with myeloproliferative disorders may be life threatening. Conventional therapy with radioisotopes and/or cytotoxic drugs may require weeks for effective control of platelet counts. In five patients, plateletpheresis by discontinuous-flow (Haemonetics) or continuous-flow (Aminco Celltrifuge) centrifugation was used as a means of reducing platelet counts acutely. With each procedure, approximately 2-9 X 10(12) platelets were removed, resulting in decrements in platelet counts and relief of symptoms. Plateletpheresis is a useful and safe acute means of controlling platelet counts in myeloproliferative disorders.     

Adjustable gastric banding as revisional bariatric procedure after failed gastric bypass—intermediate results

BackgroundAlthough gastric bypass is the most common bariatric procedure in the United States, it is has been associated with a failure rate of 15% (range 5–40%). The addition of an adjustable gastric band to Roux-en-Y gastric bypass has been reported to be a useful revision strategy in a small series of patients with inadequate weight loss after proximal gastric bypass.MethodsWe report on 22 patients who presented with inadequate weight loss or significant weight regain after proximal gastric bypass. All patients underwent revision with the placement of an adjustable silicone gastric band around the proximal gastric pouch. The bands were adjusted at 6 weeks postoperatively and beyond, as needed. Complications and weight loss at the most recent follow-up visit were evaluated.ResultsThe mean age and body mass index at revision was 41.27 years (range 25–58) and 44.8 ± 6.34 kg/m², respectively. Patients had experienced a loss of 19%, 27%, 47.3%, 42.3%, 43%, and 47% of their excess weight at 6, 12, 24, 36, 48, and 60 months after the revisional procedure, respectively. Three major complications occurred requiring reoperation. No band erosions have been documented.ConclusionThe results from this larger series of patients have also indicated that the addition of the adjustable silicone gastric band causes significant weight loss in patients with poor weight loss outcomes after gastric bypass. That no anastomosis or change in absorption is required makes this an attractive revisional strategy. As with all revisional procedures, the complication rates appear to be increased compared with a similar primary operation.     

针刺疗法治疗功能性肠疾病的研究进展

针灸在中国已经经验性的应用了数千年,而且在全世界范围越来越广泛的被医生和患者所接受．功能性胃肠疾病是临床上常见疾病．依据罗马标准,普通人群中一种以上功能性胃肠病的患病率高达70％以上．由于其病因与发病机制仍不明确,所以治疗效果尚不能令人满意．在过去的几十年里,对于针灸对于功能性胃肠疾病的治疗及可能机制做了一些研究．对探求针刺疗法对功能性胃肠疾病的潜在治疗作用有着重要的临床意义．我们对已有的关于针刺疗法对于不同功能性肠疾病的治疗效果和机制研究作一综述．     

Human herpesvirus 6: infection and disease following autologous and allogeneic bone marrow transplantation

Human herpesvirus 6 activity (HHV-6) was studied in 15 allogeneic and 11 autologous marrow transplantation patients. After transplantation, HHV-6 was isolated from the peripheral blood mononuclear cells of 12 of 26 patients (6 allogeneic and 6 autologous). All isolates were variant B. Eleven of 26 and 12 of 19 patients showed salivary shedding of HHV-6 DNA before and after transplantation, respectively. The antibody titer increased in 7 of 26 patients. Thus, 23 of 26 patients showed evidence of active HHV-6 infection either by virus isolation, salivary shedding, or increases in antibody titers. The fraction of saliva specimens positive in 19 patients was negatively associated with their antibody titers (P= .005). The proportion of cultures positive increased after transplantation (P = .007). Sinusitis was associated with HHV-6 isolation in autologous recipients (P= .002). In allogeneic patients, active human cytomegalovirus infection was associated with HHV-6 isolation (P = .04). No association was observed between HHV-6 infection and GVHD, pneumonia, delay in engraftment, or marrow suppression. Of the 120 clinical events analyzed in 26 patients, HHV-6 was defined as a probable cause of 16 events in 9 patients based on the propinquity of HHV-6 activity and the clinical event plus the absence of other identified causes of the event.     

4-间氨基酚-4去甲表鬼臼醚诱导K562细胞凋亡

目的:鬼臼毒素具有抗炎作用,为限制其对机体产生不良反应,探讨经过结构改造的4-间氨基酚-4去甲表鬼臼醚对K562细胞生长抑制及诱导凋亡情况。方法:实验于2004-03/2005-01在兰州医学院完成。①实验材料:4-间氨基酚-4去甲表鬼臼酯由兰州大学应用有机化学国家重点实验室田暄教授惠赠,纯度98%。依托铂甙(连云港恒瑞药业产品,批号04060121,20g/L)临用前以5%二甲亚砜稀释至5g/L。K562细胞由兰州大学中药新药临窗前研究重点实验室传代保种。②细胞生长抑制率检测:取K562细胞,离心后调整浓度为1×108L-1,以100μL等量接种于96孔培养板。4-间氨基酚-4去甲表鬼臼醚组分别加入0.313,0.625,1.25,2.5,5,10,20,40mg/L的4-间氨基酚-4去甲表鬼臼醚药液10μL;依托铂甙组分别加入以上8种终浓度的依托铂甙药液10μL;正常对照组加入等量的溶媒;空白对照组不加细胞和任何药物,只加入等量的完全培养液。采用噻唑蓝法检测药物与细胞作用24,48,72h时K562细胞的生长抑制率。③细胞超微结构观察:取K562细胞,离心后调整浓度为1×109L-1,以2mL等量接种于24孔培养板。4-间氨基酚-4去甲表鬼臼醚组加入2.5mg/L的4-间氨基酚-4去甲表鬼臼醚药液200μL,正常对照组加入等量的溶媒。制作超薄切片,用醋酸双氧铀、柠檬酸铅染色,透射电镜观察细胞形态及细胞质、细胞核的变化。④细胞周期及凋亡检测:取K562细胞,离心后调整浓度为1×108L-1,以2mL等量接种于24孔培养板。4-间氨基酚-4去甲表鬼臼醚组分别加入1.25,2.5,5,10,20mg/L的4-间氨基酚-4去甲表鬼臼醚药液200μL,正常对照组加入等量的溶媒。在流式细胞仪上检测细胞周期,用Multicycle软件计算凋亡细胞百分率。结果:①4-间氨基酚-4去甲表鬼臼醚抑制K562细胞生长情况:在0.313～20mg/L范围内,其对K562细胞的抑制作用随浓度升高而增强,具有量效关系,同时抑制率随着作用时间的延长而升高,具有时效关系;超过20mg/L时抑制作用逐渐下降。依托铂甙对K562细胞的抑制情况与4-间氨基酚-4去甲表鬼臼醚类似。②细胞超微结构:正常对照组K562细胞核形状规则,核膜清晰可见,内质网丰富,内含大量线粒体,细胞表面微绒毛多,染色体分布于核中央。4-间氨基酚-4去甲表鬼臼醚组K562细胞出现明显的凋亡特征,微绒毛消失,细胞浆固缩,染色体凝集为团块状分布于核膜边缘,细胞内出现大量空泡,线粒体和内质网减少,细胞周围出现凋亡小体。③细胞周期及凋亡情况:1.25,2.5,5,10,20mg/L4-间氨基酚-4去甲表鬼臼醚作用24h,分别有19.4%,34.8%,34.0%,6.9%,4.5%的K562细胞发生凋亡,G0/G1期和S期K562细胞减少,于G2/M期明显增多。正常对照组凋亡率仅为0.3%。结论:①4-间氨基酚-4去甲表鬼臼醚能够抑制K562细胞的生长,呈时效、量效关系。②4-间氨基酚-4去甲表鬼臼醚可诱导K562细胞凋亡。