In vitro and in vivo effects of prestorage filtration of apheresis platelets

BACKGROUND: The effect of prestorage filtration on the quality of apheresis platelet concentrates stored for transfusion is undetermined. STUDY DESIGN AND METHODS: Investigation of 11 plateletpheresis components used a concurrent paired-study design. On the day of collection, each component was equally divided into two suspensions; one half was filtered, and the other half was not. Each suspension was stored for 5 days. In vitro testing was performed on the day of collection (Day 0) for cell counts and on Day 5 for measurements of lactate, glucose, blood gases, pH, platelet ATP, hypotonic stress ratio, extent of shape change in response to ADP, tissue necrosis factor alpha, interleukin 8, interleukin 1 alpha, interleukin 1 beta, interleukin 6, and platelet surface glycoproteins by flow cytometry. At the end of the 5-day period, a sample was taken from each of the two suspensions, radiolabeled with either 51Cr or 111In, and transfused concurrently. Posttransfusion samples were drawn for measurements of recovery and platelet survival and for functional assessment of the ex vivo ability of the circulating radiolabeled platelets to aggregate in response to ADP. RESULTS: The apheresis component had a mean platelet yield of 3.2 +/? 0.4 × 10(11) and a white cell yield ranging from 1 × 10(5) to 1 × 10(8), with a median of 2 × 10(7). Filtration resulted in a platelet loss of approximately 10 percent and a variable 2 to 3 log10 reduction in white cell content. No significant differences between filtered and unfiltered suspensions in paired t tests that would likely have an impact on platelet quality were observed in the in vitro tests. The in vivo recovery and survival were highly similar and not statistically different in filtered and unfiltered paired suspensions: the mean difference was 1.2 +/? 4.0 percent for recovery and 7.0 +/? 15 hours for survival. The functional assessment by aggregation to ADP showed no difference between filtered and unfiltered suspensions. A small decrease in tumor necrosis factor alpha and interleukin 8 was evident in the filtered suspension as compared to levels in the unfiltered suspensions. CONCLUSION: Prestorage white cell reduction in apheresis components resulted in WBC reduction by several log10 with no evident adverse effect on platelet viability or function.     

Amifostine (WR-2721) shortens the engraftment period of 4- hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support

4-Hydroperoxycyclophosphamide (4-HC), a commonly used marrow-purging agent, is active against many tumors, but is also toxic to normal marrow progenitors. Amifostine (WR-2721) is a sulfhydryl compound with chemoprotectant activity. Preclinical studies using suspensions of bone marrow and breast cancer cells demonstrated that ex vivo treatment with amifostine followed by 4-HC resulted in protection of marrow progenitors, with no compromise in the antitumor effect of 4-HC. This fact stimulated the development of a clinical trial. Bone marrow was harvested from 15 poor-prognosis breast cancer patients and randomly assigned to ex vivo treatment with amifostine followed by 4-HC (amifostine + 4-HC), or treatment with 4-HC alone. High-dose chemotherapy was then administered followed by infusion of the purged autologous bone marrow support (ABMS). Leukocyte engraftment, defined as a white blood cell count > or = 1 x 10(9)/L, was achieved in an average of 26 days for patients whose marrow was purged with amifostine + 4-HC versus 36 days for patients whose marrow was purged with 4-HC alone (P = .032). The average number of platelet transfusions (12 v 29; P = .017) and days of antibiotic therapy (28 v 40; P = .012) were significantly less for patients whose marrow was exposed to amifostine + 4-HC, compared with 4-HC alone. Unpurged backup marrow fractions were infused into three patients whose marrow was purged with 4-HC alone, because of inadequate marrow recovery. None of the patients who received amifostine + 4-HC-purged marrow required a backup marrow fraction. Complete remissions were achieved in 83% of patients with measurable disease, with no difference between the two cohorts. Forty- three percent of patients remained alive and progression-free at a mean of 13 months posttransplant. There was no significant difference in the rate or pattern of relapse for patients whose marrow was purged with amifostine + 4-HC compared with those whose marrow was purged with 4-HC alone. Ex vivo treatment of marrow with amifostine significantly shortens the time to marrow recovery, thereby reducing the risk of myelosuppressive complications in breast cancer patients receiving high- dose chemotherapy and 4-HC-purged ABMS. Since supportive care requirements are also significantly decreased, amifostine may reduce the cost of such therapy.     

Dose-response effect of fetal cocaine exposure on newborn neurologic function

BACKGROUND: Studies of fetal cocaine exposure and newborn neurologic function have obtained conflicting results. Although some studies identify abnormalities, others find no differences between cocaine-exposed and cocaine-unexposed infants. To determine the effects of prenatal cocaine exposure on intrauterine growth and neurologic function in infants, we prospectively evaluated 253 infants shortly after birth. METHODS: Women who delivered a live singleton >36 weeks by dates were eligible for enrollment. Maternal exclusionary criteria were known parenteral drug use, alcoholism, and acquired immunodeficiency syndrome; infant exclusionary criteria were Apgar scores 相似文献   

肠球菌医院感染特征及新型抗菌药物耐药性研究

目的探讨肠球菌属细菌分布及耐药性特征,为指导临床合理用药及控制医院感染提供依据。方法对该院2011年1月至2013年12月年临床送检标本进行细菌分离培养、鉴定和药敏试验。结果共检出肠球菌属细菌140株,屎肠球菌71株(50.7%),粪肠球菌60株(42.9%),其他肠球菌9株(6.4%),其中尿液99株(70.7%);粪肠球菌对青霉素、氨苄西林、红霉素的耐药率为15.0%、12.5%和75.0%,屎肠球菌对青霉素、氨苄西林、左氧氟沙星、环丙沙星、红霉素耐药率大于80.0%,粪肠球菌和屎肠球菌对万古霉素(5.0%、4.2%)、利奈唑胺(8.4%、1.4%)极度敏感,喹奴普丁/达福普丁对粪肠球菌耐药率(100.0%)高于屎肠球菌(26.7%),达托霉素无耐药菌株。结论肠球菌属以泌尿系统感染为主,屎肠球菌检出率略大于粪肠球菌,屎肠球菌对大多数抗菌药物耐药率高于粪肠球菌,喹奴普丁/达福普丁仅对屎肠球菌有较高敏感性,万古霉素、利奈唑胺、达托霉素对肠球菌属细菌保持极高敏感性。     

CD4+CD25+调节T细胞与肿瘤免疫治疗策略

随着分子生物技术的不断发展,肿瘤的生物治疗在临床应用中的地位日渐突出,其中CD4+CD25+Foxp3+调节T细胞(CD4+CD25+Foxp3+regulatory T cell,Treg)在抑制肿瘤免疫方面起着重要作用,文章就其近年来在肿瘤免疫领域的研究进展作一综述.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

不同标准空腹血糖受损人群葡萄糖负荷后血糖代谢特征

目的：分析两种标准空腹血糖受损人群葡萄糖负荷后血糖代谢特点。方法：对3828名40岁以上居民进行流行病学调查,对空腹血糖≥5.6mmol/L者行75g葡萄糖负荷试验,据不同空腹血糖受损诊断标准分析负荷后2h血糖代谢情况。结果：在以空腹血糖为6.1mmol/L为切点诊断的245例空腹血糖受损（IFG）人群中,糖耐量减低（IGT）的患病率为41.22%,女性（25.71%）高于男性（15.51%）;2型糖尿病（T2DM）患病率为20.82%,女性（11.84%）高于男性（8.98%）。在以空腹血糖为5.6mmol/L为切点诊断的627例空腹血糖受损人群中,糖耐量减低的患病率为37.00%,女性（23.76%）高于男性（13.23%）;2型糖尿病患病率为13.88%,女性（9.52%）高于男性（4.63%）。结论：以空腹血糖为5.6mmol/L和6.1mmol/L为切点诊断的空腹血糖受损人群葡萄糖负荷后2h血糖代谢异常率分别为50.88%和62.04%,患病率女性均高于男性。     

于氨双唑钠对局部晚期非小细胞肺癌放射增敏作用的疗效观察

目的：探讨甘氨双唑钠（CMNa）对III期肺癌的放射增敏作用及不良反应。方法：采用随机分组的方法将经病理学确诊的Ⅲ期非小细胞肺癌（NSCLC）患者分为实验组（A组,放疗加甘氨双唑钠）及对照组（B组,单纯放疗）。两组放疗方法均一样。A组在放疗同时,加用CMNa（800mg／m^2）,每周3次,至疗程结束;B组为单纯放疗,评价两组疗效及观察不良反应。结果：A组的CR＋PR为82．6％（19／23）,显著高于B组的52．2％（12／23）,P〈0．05,差异有统计学意义。两组的不良反应比较,P〉0．05,差异无统计学意义。结论：甘氨双唑钠对局部晚期非小细胞肺癌有放射增敏作用．可提高有效率（CR＋PR）,但不增加不良反应。