Enhanced antitumor activity of irinotecan combined with propolis and its polyphenolic compounds on Ehrlich ascites tumor in mice.

The effects of the anticancer drug irinotecan combined with ethanolic extract of propolis (EEP), a water-soluble derivate of propolis (WSDP), quercetin and naringin on the growth of Ehrlich ascites tumor (EAT) and the life span of tumor-bearing Swiss albino mice were studied. Test components were given to mice intraperitoneally (i.p.) at doses of 100mg kg(-1) for three consecutive days before the i.p. injection of EAT cells (1x10(6)). Irinotecan was administered i.p. at dose of 50mg kg(-1) on days 1, 13, and 19 after tumor cell inoculation. The results clearly demonstrate the synergistic action of irinotecan and EEP on survival time. These results suggest that clinical trials using a propolis preparation EEP combined with irinotecan may be beneficial in maximizing antitumor activity and minimizing post-chemotherapeutic reactions to the cytostatic drug.     

Combined therapy with chemotherapeutic agents and herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) in human non-small cell lung cancer

A replication-selective herpes simplex virus type 1 ICP34.5 mutant (HSV-1716) has shown efficacy both in vitro and in vivo against human non-small cell lung cancer (NSCLC) cell lines but complete eradication of tumor has not been accomplished with a single viral treatment in our murine xenograft models. Therefore, strategies to enhance the efficacy of this treatment were investigated. We determined the oncolytic activity of HSV-1716 in NCI-H460 cells in combination with each of four chemotherapeutic agents: mitomycin C (MMC), cis-platinum II (cis-DDP), methotrexate (MTX), or doxorubicin (ADR). Isobologram analysis was performed to evaluate the interaction between the viral and chemotherapeutic agents. The oncolytic effect of HSV-1716 in combination with MMC was synergistic in two of five NSCLC cell lines. In the other three cell lines, the combined effect appeared additive. No antagonism was observed. The in vivo effect of this combination was then examined in a murine xenograft model. NCI-H460 flank tumors were directly injected with HSV-1716 (4 x 106 PFU) followed by intravenous MMC administration (0.17 mg/kg) 24 hr later. After 3 weeks, the mean tumor weight in the combined treatment group was significantly less than either individual treatment in an additive manner. The synergistic dose of MMC neither augmented nor inhibited viral replication in vitro and HSV-1716 infection did not upregulate DT-diaphorase, which is the primary enzyme responsible for MMC activation. In summary, the combination of HSV-1716 with common chemotherapeutic agents may augment the effect of HSV-based therapy in the treatment of NSCLC.     

酪氨酸激酶抑制剂HerbimycinA联合化疗药物对K562细胞凋亡…

探讨慢性髓细胞白血病细胞抗凋亡机制和诱导细胞凋亡的有效方法。方法：采用Ｋ５６２细胞培养，观察酪氨酸激酶抑制剂ＨｅｒｂｉｍｙｃｉｎＡ联合化疗药物对细胞凋主恨的影响，探讨ＨＭＡ对ＣＭＬ细胞的作用。结论ＨＭＡ通过抑制ＣＭＬ细胞内酪氨酸激酶活性促进细胞凋亡而增加对化疗药物的敏感性，表明酪氨酸激酶抑制剂作为治疗ＣＭＬ药物具有潜在应用价值。     

Angiogenesis inhibition in the treatment of colorectal cancer Part 3 of a 3-part series: targeting VEGF--current and future research directions

Treatment options for advanced colorectal have improved substantially in recent years as a number of agents have been developed that have different targets and mechanisms of action. Significant improvements in outcomes have been observed by combining multiple chemotherapeutic agents instead of the single-agent approach. Some debate still remains regarding which combination is most effective and in what order regimens should be given. In addition to cytotoxic chemotherapy drugs, targeted biologic agents have been developed to inhibit tumor angiogenesis, which may hamper the viability of the tumor. There may also be a synergistic effect between antiangiogenic agents and chemotherapy. Regulation of tumor angiogenesis may actually improve blood flow throughout the tumor, which could enhance delivery of chemotherapy through the circulation. One antiangiogenic agent currently approved for the treatment of advanced colorectal cancer is bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, a ligand known to be important for angiogenesis. The other currently approved biologic agent, cetuximab, targets the epidermal growth factor receptor. The combination of bevacizumab plus cetuximab has a biologic rationale. Randomized trials incorporating combination chemotherapy regimens plus both bevacizumab and cetuximab are currently underway, as are preliminary studies withnovel angiogenesis inhibitors.     

酪氨酸激酶抑制剂 Herbimycin A 联合化疗药物对 K562 细胞凋亡的影响

目的：探讨慢性髓细胞白血病（ＣＭＬ）细胞抗凋亡机制和诱导ＣＭＬ细胞凋亡的有效方法。方法：采用Ｋ５６２细胞培养，观察酪氨酸激酶抑制剂ＨｅｒｂｉｍｙｃｉｎＡ（ＨＭＡ）联合化疗药物对ＣＭＬ细胞凋亡的影响，探讨ＨＭＡ对ＣＭＬ细胞的作用。结果：ＨＭＡ或化疗药物单独应用可抑制Ｋ５６２细胞增殖，但不能明显诱导其凋亡。ＨＭＡ能明显增强化疗药诱导Ｋ５６２细胞凋亡。加入外源性巯基化合物阻断ＨＭＡ与酪氨酸激酶的结合可完全取消这种作用。结论：ＨＭＡ通过抑制ＣＭＬ细胞内酪氨酸激酶活性促进细胞凋亡而增加对化疗药物的敏感性，表明酪氨酸激酶抑制剂作为治疗ＣＭＬ药物具有潜在的应用价值。     

I-J+ suppressor cells are probably involved in regulation of spleen colony formation by hematopoietic stem cells (CFUs)

Treatment of murine bone marrow and spleen cell suspensions with anti-I-Jk alloantiserum and complement resulted in an increased number of CFUs (revealed by Till and McCulloch exocolonization technique) compared with controls. The stimulatory effect was observed with 7-8 day CFUs and was negligible or absent with 11-12 day CFUs. Normal thymus cells treated with anti-I-Jk antiserum plus complement would augment the colony-forming potential of normal marrow cells.     

The role of spermidine/spermine N1-acetyltransferase in determining response to chemotherapeutic agents in colorectal cancer cells

Polyamines have been shown to play a role in the growth and survival of several solid tumors, including colorectal cancer. We identified the polyamine catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) as being one of the most highly inducible genes in two DNA microarray screens to identify novel determinants of response to chemotherapeutic agents in colorectal cancer. SSAT was shown to be inducible in response to 5-fluorouracil (5-FU) or oxaliplatin in parental and drug-resistant HCT116 cell lines. It was also shown that SSAT mRNA was up-regulated in response to 5-FU or oxaliplatin in a panel of six colorectal cancer cell lines. The polyamine analogue N(1),N(11)-diethylnorspermine (DENSpm) depletes polyamine pools and potently induces SSAT. We evaluated the effect of combining DENSpm with chemotherapeutic agents in HCT116 p53(+/+) cells and in HCT116 drug-resistant daughter cell lines. Western blot analyses showed that SSAT protein expression was dramatically enhanced when DENSpm was combined with oxaliplatin or 5-FU in HCT116 p53(+/+) cells. Using cell viability assays and flow cytometry, synergistic induction of cell death was observed following cotreatment of HCT116 p53(+/+) cells with DENSpm and each chemotherapeutic agent. Of note, this combined therapy increased the chemosensitivity of cells rendered resistant to each of these chemotherapeutic agents. Small interfering RNA-mediated down-regulation of SSAT resulted in loss of synergy between DENSpm and these agents. These results show that SSAT plays an important role in regulating cell death following combined cytotoxic drug and DENSpm treatment. Furthermore, DENSpm sensitizes both sensitive and resistant cells to chemotherapeutic agents. Taken together, these results suggest that SSAT may be an important target for therapeutic intervention in colorectal cancer.     

Long-lasting anti-metastatic efficiency of interleukin 12-encoding plasmid DNA

Intramuscular injection of plasmid DNA encoding both subunits of the cytokine interleukin 12 (IL-12) exhibits strong antimetastatic activity against lung metastases induced by the malignant melanoma cell line B16-F10. The protective effect of IL-12 DNA is long-lasting, since administration of tumor cells 9 days after IL-12 DNA treatment prevented metastasis formation. No effects were observed with empty plasmid controls, DNA encoding the melanoma-associated antigen pmel17/gp100, the granulocyte-macrophage colony-stimulating factor GM-CSF, B7.1, or CpG-containing oligodeoxynucleotides. IL-12 DNA is required during early phases of metastasis formation and is ineffective when administered later. Its efficiency is dose dependent. The cytotoxic T cell response contributes to the antimetastatic effect as evidenced by genetically modified CD8- or perforin knockout mice. Depletion of natural killer (NK) cells by antibodies completely abrogated the effect. In contrast, the IL-12-induced antimetastatic effect was not mediated by interferon gamma (IFN-gamma) or tumor necrosis factor alpha (TNF-alpha) as shown with IFN-gamma receptor and TNF-alpha knockout mice, respectively. Toxic side effects by IL-12 were low. Our results suggest that plasmid DNA encoding IL-12 might have potential value as gene medicine against the initiation of metastasis formation.     

Validation of BacT/ALERT plastic culture bottles for use in testing of whole-blood-derived leukoreduced platelet-rich-plasma-derived platelets

BACKGROUND: Bacterial detection of platelet (PLT)-rich-plasma (PRP)-derived PLTs presents unique challenges for countries that do not allow pooling before storage. This study validated the BacT/ALERT for use in testing pooled PRP-derived PLTs with nine contaminating organisms. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes were inoculated into two PRP-derived PLT pools (target, 10 and 100 colony-forming units [CFUs]/mL; actual recovered concentrations, 5 and 90 CFUs/mL). Four milliliters of each postbacterial inoculation sample was inoculated into both plastic aerobic and anaerobic bottles and 0.5 mL was plated onto blood agar. RESULTS: All organisms (excluding P. acnes) were detected in 8.2 to 22.0 and 7.6 to 20.3 hours (10 and 100 CFUs/mL, respectively) and the mean time to detection was 15.0 and 13.1 hours (10 and 100 CFUs/mL, respective). P. acnes was detected with the anaerobic bottles in a mean of 74.9 and 64.3 hours (10 and 100 CFUs/mL, respectively). With E. cloacae, E. coli, K. pneumoniae, S. marcescens, and S. viridans detection with the anaerobic bottles was faster or equivalent to the detection with the aerobic bottles. This was most notable with S. viridans where the anaerobic bottle was reactive on average 21.6 and 10.8 hours (10 and 100 CFUs/mL, respectively) faster than the aerobic bottle. CONCLUSIONS: This study validates the use of the BacT/ALERT system for the detection of bacteria in PRP-derived PLTs in a pooled format. Overall, the use of the BacT/ALERT system allowed the detection of pooled PRP-derived PLTs inoculated with nine bacteria at 10 and 100 CFUs per mL in 7.6 to 22.0 hours (excluding P. acnes).     

Adjuvant effect of clarithromycin on chemotherapy for murine lung cancer

Clarithromycin (CAM) increased the median survival of patients with unresectable non-small-cell lung cancer who had received chemotherapy and/or radiotherapy [Chemotherapy 1997;43:288-296]. The present study was performed to ascertain whether CAM alone exhibits an antitumor effect against Lewis lung carcinoma (LLC) and to analyze the nature of its adjuvant effect on LLC-inoculated C57BL/6 mice. CAM at 10 mg/kg/day retarded the growth of subcutaneously inoculated LLC cells; consequently, the mean survival time of mice with LLC increased. This treatment was also effective in reducing the number of tumor nodules in the lung after intravenous inoculation with LLC cells. When tumor-bearing mice received an intravenous injection of vindesine sulfate (7 mg/kg) and cisplatin (6 mg/kg) 7 days after tumor inoculation, the chemotherapeutic effect was significantly enhanced by CAM treatment when it started 7 days after chemotherapy, but not when it started the day after chemotherapy. The delayed initiation of CAM treatment resulted in the enhancement of natural killer cell activity and CD8+ T cell cytotoxicity and increased the number of interferon-gamma-producing T cells and interleukin-4-producing T cells. These findings indicate that CAM can exhibit an antitumor effect by itself and also induce the well-balanced expansion of helper T cell subsets in tumor-bearing mice recovering from the immunosuppression caused by chemotherapy. CAM may therefore be a promising adjuvant drug in anticancer chemotherapy, and treatment with this macrolide should be initiated at some interval after basic cancer therapy.     

Bradykinin modulation of tumor vasculature: I. Activation of B2 receptors increases delivery of chemotherapeutic agents into solid peripheral tumors, enhancing their efficacy

Delivery of chemotherapeutic agents to solid peripheral tumors is compromised because the impaired microvasculature within and surrounding tumors limits diffusion and convection of agents from the vasculature to the tumor. Using a variety of rat tumor models, we show that intravenous administration of a vasoactive bradykinin B2 receptor agonist (Cereport, or labradimil; formerly RMP-7) enhances by nearly 3 times the delivery of the chemotherapeutic agent carboplatin, as well as the larger 70-kDa marker dextran, into ectopic and orthotopic solid tumors. This effect was selective for tumor tissue, with little or no increase seen in nontumor tissues and organs. Additionally, the increased carboplatin levels observed in tumors persisted for at least 90 min (the longest time point measured). In contrast to the consistent effects with hydrophilic compounds, delivery of the lipophilic, high protein-binding chemotherapeutics paclitaxel and 1,3-bis[2-chloroethyl]-1-nitrourea (BNCU) was not enhanced. Administration of Cereport with either carboplatin or another hydrophilic chemotherapeutic agent, doxorubicin, significantly increased efficacy of both agents, manifested by suppression of tumor growth and prolonged survival in tumor-bearing rats. These data demonstrate that delivery of chemotherapeutics to tumors can be pharmacologically increased (by stimulating bradykinin B2 receptors) without increasing the systemic exposure, or therefore, the toxic liability associated with higher chemotherapeutic doses.     

Synthesis and application of a non-viral gene delivery system for immunogene therapy of cancer.

The synthesis and gene delivery application of a novel lipopolymer, PEG-PEI-CHOL (PPC), is described. PPC is composed of a low molecular weight branched polyethylenimine (PEI) covalently linked with functional groups methoxypolyethyleneglycol (PEG) and cholesterol (CHOL). The potential utility of PPC as a gene delivery polymer was evaluated by showing its ability to form stable nanocomplexes with DNA, protect DNA from degradation by DNase and mediate gene transfer in vitro and in vivo in solid tumors. The ratio of PEG/PEI/CHOL and nitrogen to phosphate (Polymer/DNA) was optimized for physico-chemical properties and gene delivery efficiency of PPC/DNA complexes. The gene therapy application of the polymer was shown following administration of a murine IL-12 plasmid (pmIL-12) formulated with PPC into tumors in mice which resulted in significant inhibition of tumor growth. The inhibitory effects of pmIL-12/PPC were enhanced when combined with specific chemotherapeutic agents, demonstrating the potential usefulness of pIL-12/PPC as an adjuvant therapy for cancer treatment.     

大肠癌患者年龄及性别与肿瘤细胞存活率的相关性

背景应用抗肿瘤药物治疗(简称化疗)已成为大肠癌患者的重要辅助治疗方法,然而对化疗药物的敏感性存在较大的个体差异,其差异是否与患者的年龄及性别有关?目的采用流行病学调查方法探讨根据肿瘤细胞存活率对药物在不同年龄以及不同性别之间大肠癌患者中的作用有否差异.设计以病理标本为研究对象的对照实验研究.单位一所医学院附属医院普外科.对象以2001-01/2003-01川北医学院附属医院普外科收治的169例大肠癌患者的癌肿标本为研究对象(均经手术切除和病理证实).患者男97例,女72例.所有病例术前均未使用抗癌药物.方法用体外肿瘤药敏试验四唑盐比色法对169例新鲜人大肠癌标本进行化疗药物敏感性检测,分析在患者不同年龄及不同性别之间的差异.主要观察指标肿瘤细胞经各种抗癌药物作用72 h后的吸光度值.结果大肠癌患者化疗药物的敏感性与不同年龄以及不同性别的差异均无显著性意义(P＞0.05).结论大肠癌患者对化疗药物敏感性的个体差异与患者的年龄及性别无关,针对大肠癌不同个体筛选敏感药物可不考虑年龄及性别因素.     

Potentiation of radioresponse by polymer-drug conjugates.

Although combined chemotherapy and radiotherapy has produced significantly improved response and survival rates among cancer patients, there is still a compelling need to establish the most effective way to deliver these agents. We hypothesize that the radiosensitizing effect of a chemotherapeutic agent can be further enhanced if the drug is delivered at an optimal concentration and is maintained in the tumor for a prolonged period. Using a water-soluble poly(L-glutamic acid)-conjugated paclitaxel (PG-TXL) as a model compound, we investigated whether paclitaxel delivered by means of polymeric carrier could increase the tumor's response to radiation. Mice bearing 8-mm syngeneic ovarian carcinoma OCa-1 tumors implanted intramuscularly were treated with i.v. injected PG-TXL alone or in combination with single doses of local radiation. The enhancement factors at 24 h interval, as measured by incremental tumor growth delay compared with radiation alone, ranged from 2.48 to 4.28. The values varied as a function of radiation dose. The enhancement of radioresponse is also a function of time interval between injection of PG-TXL and tumor irradiation. The enhancement factor increased with decreasing interval, suggesting that radiation may in turn mediate the sensitivity of tumor toward PG-TXL. Thus, the mechanism of PG-TXL's radiopotentiation activity is probably multifactorial. Remarkably, while combined radiation and TXL produced additive or even sub-additive interaction when radiation preceded TXL injection, combined radiation and PG-TXL produced synergistic interaction in a mammary MCa-4 tumor model. Radiation significantly increased tumor uptake of PG-TXL, suggesting a potential role of radiation-modulated antitumor activity of polymeric drugs. Our data support a treatment strategy combining radiation and polymeric chemotherapy that may have important clinical implications in terms of scheduling and optimization of the therapeutic ratio.     

Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, an essential precursor for isoprenoid compounds in mammalian cells. Recent studies have shown that mevinolin, a competitive inhibitor of the reductase, inhibits cell proliferation and induces differentiation in cultured C1300 (Neuro-2A) murine neuroblastoma cells. We now report that mevinolin can inhibit neuroblastoma growth in vivo. The specific activity of HMG-CoA reductase in subcutaneous neuroblastomas increased more than 20-fold between the fifth and eighth days after tumor inoculation, and remained elevated for the remainder of the tumor lifetime in mice. The increase in reductase activity was correlated with a marked increase in tumor DNA content and exponential increase in tumor weight. Using an in vitro assay to monitor the ability of mouse serum to suppress sterol synthesis, we determined that mevinolin was inactivated or cleared from the circulation within 3-6 h after a single subcutaneous injection. However, by using subcutaneous osmotic pumps to deliver a constant infusion of mevinolin, we were able to maintain adequate blood levels of the drug for 7 d. Mevinolin (5 mg/kg per h) suppressed tumor growth (wet weight) significantly when treatment was carried out between day 1 and day 8 or between day 5 and day 12 after tumor inoculation. Histopathological examination of tumors from mevinolin-treated mice revealed few or no mitotic figures and marked cellular degeneration. Measurements of incorporation of (3H)acetate into neuroblastoma sterols and ubiquinones 24 h after implantation of osmotic pumps showed that mevinolin produced a marked inhibition of isoprenoid synthesis in the tumors in vivo. The data suggest that, in addition to their demonstrated utility as cholesterol-lowering drugs, competitive inhibitors of HMG-CoA reductase may have considerable potential as novel antineoplastic agents.     

A humanized monoclonal antibody to carcinoembryonic antigen, labetuzumab, inhibits tumor growth and sensitizes human medullary thyroid cancer xenografts to dacarbazine chemotherapy

A variety of observations have shown that carcinoembryonic antigen (CEA) is associated with growth and metastasis of cancers, including correlation of CEA serum levels with poor clinical outcome, mediation of cell-cell adhesion by CEA, and involvement of CEA in the immune recognition of tumors and apoptotic pathways. The purpose of this study was to investigate the effect that an anti-CEA monoclonal antibody (MAb) may have on the growth of medullary thyroid cancer (MTC), a CEA-expressing tumor, alone and in combination with chemotherapy. Antitumor effects were evaluated in a nude mouse-human MTC xenograft model. Using the TT MTC cell line grown s.c., we compared tumor growth in untreated mice with that of mice given the humanized anti-CEA MAb labetuzumab or an isotype-matched control MAb. The effects of time of administration post-tumor injection, MAb dose response, specificity of response, and combination with dacarbazine (DTIC) chemotherapy were studied. The humanized anti-CEA MAb, labetuzumab, has direct, specific, antitumor effects in this model, without conjugation to a cytotoxic agent. In addition, labetuzumab sensitizes these tumor cells to chemotherapy with an effective drug in this model, DTIC, without increased toxicity. Significant delays in tumor growth were caused by the MAb therapy or chemotherapy alone; however, the combination of these agents was significantly more effective than either agent given as a monotherapy or use of an irrelevant MAb in this model. The superiority of the combined modality treatment argues for the integration of CEA MAb therapy into chemotherapeutic regimens for MTC management and possibly other CEA-expressing neoplasms.     

Effects of ethanol on pulmonary inflammation in postburn intratracheal infection

Infectious complications are a major cause of mortality in trauma patients. Burn patients with prior ethanol exposure have a worse prognosis than those who sustain injury but had not been drinking. We examined pulmonary infection and lung pathology in mice given ethanol (1.2 g/kg) 30 minutes before being subjected to 13 to 15% total body surface area scald burn followed by intratracheal inoculation with Pseudomonas aeruginosa (1-2 x 10(3) colony-forming units [CFUs]). Survival was monitored for up to 48 hours. Sham control groups had 100% survival after intratracheal infection regardless of ethanol exposure. Infected burned animals had 55% survival; however, survival of infected mice exposed to ethanol and burn injury was significantly lower (27%, P < .0001). When pulmonary infection was evaluated, the lungs of sham groups were negative for bacterial colonies. In addition, at 24 hours there were no significant differences in lung CFUs from infected burned animals regardless of ethanol exposure (3.0 x 10(4)). However, pulmonary bacterial content significantly decreased (1.2 x 10, P < .02) at 48 hours in mice given burn injury alone, where CFUs from the lungs of mice exposed to ethanol prior to burn did not decline (5.4 x 10(5)). At the same time point, lungs from animals given ethanol and burn injury had about a 2-fold (P < .02) increase in leukocyte infiltration and vascular congestion, as well as decreased pulmonary oxygen saturation (82.8%, P < .02), when compared with other treatment groups. In summary, ethanol exposure in postburn intratracheal infection results in the inability to clear pulmonary infection marked by a prolonged pulmonary leukocyte accumulation and a decrease in pulmonary function.     

Lymphocytes anticancer chemosensitivity testing in vitro--an approach to predict immunosuppressive effect of anticancer agents

In an attempt to predict immunosuppression by chemotherapy, an in vitro lymphocytes chemosensitivity assay was developed. The effect of mitomycin C (MMC), carboquone (CQ), adriamycin (ADR) and 5-fluorouracil (5-FU) on spleen cells of BALB/c mice were assessed by phytohemagglutinin (PHA) response inhibition assay. ADR and 5-FU highly suppressed PHA response, whereas MMC or CQ had only a slight influence. The administration of ADR or 5-FU to mice resulted in a significant decrease of peripheral blood lymphocytes and cortical thymocytes in number, and pretreatment with ADR or 5-FU prior to tumor inoculation shortened the survival time of the mice. All these four agents highly suppressed in vitro DNA synthesis of MOPC-104E plasmacytoma, but ADR or 5-FU did not induce complete regression of the tumor. MMC or CQ induced complete regression of MOPC-104E, but they did not induce complete regression of the tumor transplanted in athymic nude mice. These results suggest that T cells participate in tumor regression and immunosuppression reduces antitumor activity of the host and that PHA response inhibition assay may be useful to predict immunosuppressive effect of anticancer agents.     

盐酸利多卡因和地塞米松磷酸钠在预防化疗药物外渗中的应用

目的探讨盐酸利多卡因和地塞米松磷酸钠在预防化疗药物外渗中的作用。方法选择142例血管细、弹性差、多次静脉输液治疗的患者，随机分成治疗组和对照组。治疗组在输入化疗药物前先用2％盐酸利多卡因1ml、地塞米松磷酸钠5mg（2ml）加7ml生理盐水稀释缓慢静脉推注后，再输入化疗药物；对照组在化疗前静脉注入10ml生理盐水。结果治疗组Ⅰ期、Ⅱ期药物外渗发生率分别为8．5％和0，而对照组分别为26．8％与4．2％，两组差异有统计学意义（P〈0．05）；治疗组疼痛发生率分别为15．5％和1．4％，对照组分别为36．6％与9．9％，两组间差异有统计学意义（P〈0．05）。结论对于血管细、弹性差以及多次应用化疗药物的患者，化疗前应用盐酸利多卡因和地塞米松磷酸钠缓慢静脉推注，能显著减少化疗药物外渗和静脉炎的发生；同时，应加强观察及护理。     

Enhancement of a culture-based bacterial detection system (eBDS) for platelet products based on measurement of oxygen consumption

BACKGROUND: An enhanced bacterial detection system (Pall eBDS) was developed that distinguishes itself from its predecessor (Pall BDS) by removal of the platelet (PLT)-retaining filter allowing for optimal bacterial transfer, modification of the culture tablet to reduce the confounding effects of respiring PLTs while enhancing bacterial growth, and facilitation of nutrients and gas exchange by agitating the sample pouch during incubation at 35 degrees C. The objective was to evaluate the performance of the new eBDS. STUDY DESIGN AND METHODS: Leukoreduced whole blood-derived PLT concentrates (LR-PCs) and LR single-donor PLTs (LR-SDPs) were inoculated with 1 to 15 colony-forming units (CFUs) of bacteria per mL in studies of each of 10 bacterial species associated with fatal transfusion-transmitted bacterial infection. Immediately after inoculation and after 24 hours of storage at 22 degrees C, samples of inoculated LR-PCs were aseptically transferred into the eBDS pouches. Pouches were then incubated for 24 hours at 35 degrees C with agitation and oxygen concentration was then measured. RESULTS: Median inoculation levels ranged from 5 to 13 CFUs per mL for each species studied. No significant differences in oxygen concentration were found when comparing LR-PCs with LR-SDPs. When sampling occurred from the PLTs 24 hours after inoculation, all 280 cases (24-33 replicates of each species) were detected as contaminated by the device (100% sensitivity). No false-positives were obtained with 713 uninoculated PLT units. CONCLUSIONS: The eBDS demonstrated improved detection sensitivity in the range of 1 to 15 CFUs per mL with no observed false-positives compared to the original BDS (detection range 100 to 500 CFUs/mL) with no false-positives.