Lethal interaction between heat and methylene blue in Escherichia coli.

Hyperthermia treatment is shown to act synergistically with methylene blue (MB), from the end point of lethality in Gram-negative Escherichia coli bacteria. That this lethality is correlated to the damage produced in DNA by the dye is deduced from the fact that bacteria differing in capacity for repair are almost equally sensitive to heat, but differ considerably in sensitivity to concomitant heat and dye treatment. It is demonstrated that the damage is repairable by the excision-repair system. The role of temperature seems to be that of facilitating the incorporation of the dye, which enables the latter to intercalate into the DNA. Ability of the outer membrane of E. coli AB1157 bacteria to act as a barrier to the penetration of MB remains almost intact up to 46 degrees C, but above this temperature it seems to disrupt abruptly (but reversibly), leading to inactivation of the cells by the dye. Since hyperthermia is in current use for the treatment of cancer, it is suggested that if this synergism also exists in mammalian cells, MB could eventually be used independently of its photodynamic action as an adjuvant in cancer therapy.     

亚甲蓝染色内镜诊断Barrett食管的研究进展

近年来西方国家食管贲门交界部腺癌的发病率显著升高。研究认为,Barrett食管是食管腺癌最重要的癌前病变。准确的早期诊断和有效随访是提高Barrett食管患者生存率的重要环节。目前对Barrett食管的诊断主要依靠内镜和病理,即内镜下任何长度的食管黏膜出现柱状上皮样改变并经病理确诊为特异性肠化上皮。但由于早期病灶的微小性和局灶性,内镜下准确的识别特异性肠化上皮及不典型增生在临床上仍比较困难。亚甲蓝染色内镜利用亚甲蓝可以被吸收活跃的细胞吸收着色的原理,通过内镜下喷洒对胃肠道黏膜进行染色,提高内镜对胃肠道黏膜结构的观察能力,有助于内镜医师对肠化上皮的鉴别,但是否可以提高Barrett食管的检出率还存在争议。     

Encephalopathy after cyclophosphamide with response to methylene blue

We present two cases of encephalopathy occurring after chemotherapy containing cyclophosphamide. Patient 1 was receiving vincristine, cisplatin and cyclophosphamide for recurrent medulloblastoma, whilst patient 2 received cyclophosphamide‐containing chemotherapy as adjuvant treatment for early breast cancer. After cumulative doses of 2.8 and 6 g/m² of cyclophosphamide both patients developed a gradual onset of fluctuating attention, slowed mentation and decreased consciousness. Extensive investigations excluded other causes of this altered conscious state. Given the similarity of presentation to ifosfamide encephalopathy, methylene blue (50 mg i.v.) was administered. Patient 1 experienced an immediate improvement that was not sustained, with a subsequent deterioration over several weeks and became unresponsive before death. Patient 2 experienced a dramatic improvement within 3 h and received a second dose of methylene blue with further improvement. To our knowledge, cyclophosphamide has not previously been implicated as a cause of encephalopathy. A review of the literature is presented. We hypothesize that cyclophosphamide may rarely cause encephalopathy and may also contribute to the cognitive dysfunction reported in association with chemotherapy for breast cancer and non‐Hodgkin’s lymphoma.     

蓝染法定位切除无肿块乳腺病灶的意义

背景与目的：随着乳腺影像技术的进步和推广,临床触诊未发现乳腺肿块而影像学检查发现高度可疑恶性病灶者越来越多。本研究旨在探讨乳腺钼靶立体定位美蓝染色引导切除活检对诊治这一类病灶的意义。方法：选取2002年8月至2006年10月中山大学肿瘤防治中心在临床触诊不到肿块而影像学检查发现高度可疑恶性乳腺病灶的患者138例。术前,在钼靶立体定位引导下注射少量美蓝到可疑病灶。以乳头为参照确定活检切口,将蓝染的乳腺组织切除。标本切除后,行标本钼靶照片并与原乳腺片对照,以确定切除的准确性。然后,按病理结果作相应处理。结果：全组138例患者通过上述方法均将可疑病灶准确切除。经病理检查84例（60．9％）诊断为乳腺癌,54例（39．1％）为良性病变。手术切口平均长度4．3cm,切除标本平均重量为42g。全组病例的切口均I期愈合。结论：对临床上无乳腺肿块而影像学检查发现高度可疑恶性的病灶应行切除活检。钼靶立体定位美蓝染色引导切除活检是一种准确率高、创伤性小且简单、价廉的方法,值得推广。     

Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature

Ifosfamide is an alkylating agent used in the treatment of a variety of solid tumours. Ten to 15% of patients treated with ifosfamide develop an encephalopathy. Methylene blue (MB) may be used in the treatment of this encephalopathy. The purpose of this study was to evaluate the neuroprotective effect of MB in these patients and to review the literature. Between 1993 and 1997, 52 patients (age 16-77 years) with solid tumours were treated with ifosfamide in dosages ranging from 3 to 5 g m(-2) q3w when given in combination schedules and up to 12 g m(-2) q4w when given as a single agent. Twelve patients developed central nervous system (CNS) depression, defined as National Cancer Institute Common Toxicity Criteria (NCI-CTC) neurocortical toxicity grade 2 or higher. Eight were treated with MB at a dose of 6 x 50 mg day(-1) intravenously (i.v.). Four recovered fully within 24 h, two recovered partially after 24 h and completely after 48 h while two recovered only after 72 h. Four patients did not receive MB and all recovered only after 48 h. Three patients received prophylaxis with MB at a dose of 4 x 50 mg day(-1) i.v. for the subsequent chemotherapy cycles. Two developed milder encephalopathy; one had no CNS depression at all. We conclude that MB is an effective treatment for ifosfamide-induced encephalopathy. Our findings suggest that it may also be used as a prophylactic agent.     

Photodynamic fungicidal efficacy of hypericin and dimethyl methylene blue against azole‐resistant Candida albicans strains

Antimicrobial photodynamic therapy (aPDT) is an emerging alternative to treat infections based on the use of photosensitisers (PSs) and visible light. To investigate the fungicidal effect of PDT against azole‐resistant Candida albicans strains using two PSs with a different mechanism of action, hypericin (HYP) and 1,9‐dimethyl methylene blue (DMMB), comparing their efficacy and the reactive oxygen species (ROS) species involved in their cytotoxicity. Azole‐resistant and the azole‐susceptible C. albicans strains were used. Solutions of 0.5 and 4 McFarland inoculum of each Candida strain were treated with different concentrations of each PS, and exposed to two light‐emitting diode light fluences (18 and 37 J cm^?2). Mechanistic insight was gained using several ROS quenchers. The minimal fungicidal concentration of HYP for ≥3 log₁₀ CFU reduction (0.5 McFarland) was 0.62 μmol l^?1 for most strains, whereas for DMMB it ranged between 1.25 and 2.5 μmol l^?1. Increasing the fluence to 37 J cm^?2 allowed to reduce the DMMB concentration. Higher concentrations of both PSs were required to reach a 6 log₁₀ reduction (4 McFarland). H₂O₂ was the main phototoxic species involved in the fungicidal effect of HYP‐aPDT whereas ¹O₂ was more important for DMMB‐based treatments. aPDT with either HYP or DMMB is effective in killing of C. albicans strains independent of their azole resistance pattern. HYP was more efficient at low fungal concentration and DMMB at higher concentrations.     

亚甲蓝在乳腺癌前哨淋巴结活检中的应用

目的探讨亚甲蓝作为蓝染料在乳腺癌前哨淋巴结活检中的应用价值。方法对已确诊的72例乳腺癌病人亚甲蓝皮下注射后行腋窝前哨淋巴结切除,送冰冻病理检查,再行乳腺癌改良根治术,并常规腋窝淋巴结清扫,术后病理石腊切片检查前哨淋巴结及手术切除标本。结果本组病例中68例共检出前哨淋巴结132枚,失败4例。前哨淋巴结的检出率94.4%,准确率91.8%,敏感度92%,假阴性率8%,假阳性率为0。结论采用亚甲蓝作为蓝染料应用于乳腺癌前哨淋巴结活检术,其前哨淋巴结活检的各项指标与其他蓝染料(专利蓝)相当,且材料广泛、费用低廉,具有临床应用前景。     

宫颈癌前哨淋巴结检测的初步探讨

背景与目的：近几年已开展宫颈癌前哨淋巴结(sentinel lymph node,SLN)的研究,目前影响宫颈癌SLN的检出还存在很多未知因素。本研究使用亚甲蓝作为示踪剂检测宫颈癌SLN,分析影响SLN检出的因素。方法：41例宫颈癌Ⅰbt～Ⅲb)期患者,术前90～400min在宫颈瘤周分4～6点注射亚甲蓝2～4ml,蓝染淋巴结即定为SLN,术后将SLN行多层切片HE染色和细胞角蛋白(cytokeratin,CK)免疫组化,其余淋巴结作常规病理检查,根据SLN检出率、假阴性率来探讨使用亚甲蓝检测宫颈癌SLN的影响因素。结果：41例中,31例成功定位出SLN共85枚,总检出率为75．6％,最常见部位为闭孔窝淋巴结。其中未行术前放化疗者检出率为87．0％(20／23);已行术前放化疗者检出率为61．1％(11／18)。27例注射亚甲蓝量为2～3ml的患者检出率仅为63．0％(17／27),显著低于注射量为3．4～4ml的患者(100％,14／14)。病理结果示：一共8例患者有盆腔淋巴结转移。结论：使用亚甲蓝检测宫颈癌SNL的注射剂量以3～4ml为宜。宫颈癌SLN定位个体差异较大,以闭孔窝最多见。     

亚甲蓝示踪在乳腺癌前哨淋巴结活检中的应用及影响因素

背景与目的:示踪剂的选择是影响乳腺癌前哨淋巴结活检成功与否的重要因素之一.本研究探讨亚甲蓝作为示踪剂在乳腺癌前哨淋巴结活检中的应用价值.并分析影响其示踪结果的各项因素.方法:选取2005年3月至2006年2月复旦大学附属肿瘤医院治疗的101例可手术乳腺癌患者作为研究对象,临床体检腋窝淋巴结阴性,均单独采用亚甲蓝作为前哨淋巴结活检示踪剂.前哨淋巴结活检后均行腋窝淋巴结清扫.应用石蜡连续切片、HE染色进行病理诊断.结果:本组前哨淋巴结检出率为96.04%(97/101),假阴性率为11.76%(4/34),术前未行化疗患者的假阴性率为7.40%(2/27).平均检出前哨淋巴结2.05枚.前哨淋巴结的大小与病理结果相关.病理类型、新辅助化疗、局部切除活检对本组前哨淋巴结的检出率均无影响.前哨淋巴结数量与假阴性率相关;体重指数(body mass index.BMI)对检出率、假阴性率均有影响.本组患者未发生过敏反应及皮肤坏死.结论:亚甲蓝作为乳腺癌前哨淋巴结活检的示踪剂安全、可靠;对于BMI较高的患者,需要进一步改进示踪方法.     

纳米炭混悬注射液与亚甲蓝注射液在早中期乳腺癌前哨淋巴结活检中的应用

目的 探讨纳米炭混悬注射液在乳腺癌前哨淋巴结(SLN)活检中的应用价值和优势.方法 随机将无腋窝淋巴结(ALN)转移的T1N0M0～T2N0M0乳腺癌患者116例分为两组,分别给予亚甲蓝注射液和纳米炭混悬注射液示踪.其中亚甲蓝组51例,纳米炭组65例.在摘取SLN后进行乳腺癌保乳根治术或乳腺癌仿根治术,对全部ALN进行清扫,比较两组患者中SLN的检出率、假阴性率、特异性、准确率及灵敏度.结果 亚甲蓝组SLN检出率为88.2%,假阴性率为13.3%,灵敏度为86.7%,准确率为84.3%,特异性为100%;纳米炭组SLN检出率为98.5%,假阴性率为8.7%,灵敏度为91.3%,准确率为95.4%,特异性为100%.纳米炭组的检出率及准确率明显高于亚甲蓝组(P＜0.05),纳米炭组与亚甲蓝组的假阴性率、灵敏度和特异性差异无统计学意义(P＞0.05).结论 与亚甲蓝注射液相比,纳米炭混悬注射液的稳定性和可操作性较强.

Abstract：

Objective To compare the efficacy of methylene blue versus carbon nanopartIcles suspension injection as a tracer for sentinel lymph node detection in breast cancer and the factors associated with the definition of sentinel lymph node biopsy. Methods One hundred and sixteen patients with early breast cancer underwent intraoperative sentinel lymph node biopsy, among them 51 patients accepted injection of methylene blue dye, while 65 patients received carbon nanopartIcles suspension injection. The mapping procedures and SLNB were performed using subareolar or peritumoral injection of methylene blue or carbon nanopartIcles suspension injection at the site of the primary breast cancer, followed by the axil lary lymph node dissection (ALND). All the SLN and ALN were evaluated pathologically post-operatively.Results In the MB group, the false-negative, sensitivity, accuracy, specificity rate of SLNB detection were 88.2%, 13.3%, 86.7%, 84. 3%, and 100%, respectively. In the CNP group, the false-negative,sensitivity, accuracy, specificity rate of SLNB detection were 98.5%, 8.7%, 91.3%, 95.4%, and 100%,respectively. The false-negative, sensitivity, specificity rate in the CNP group were trended to be higher than those in the MB group, but the difference of the accuracy and detection rates are significant ( P ＜ 0.05 ).Conclusions Compared with methylene blue solution, the carbon nanoparticle injection shows a better stability and operability for the sentinel lymph node detection in breast cancers.     

彩色多普勒超声引导下亚甲蓝边界定位法在乳腺癌保乳手术中的应用价值

目的探讨术前彩色多普勒超声引导下应用亚甲蓝定位肿瘤边界在乳腺癌保乳手术中的效果。方法收集2015年5月至2017年12月拟行保乳手术的乳腺癌患者120例,随机分为观察组和对照组各60例。观察组术前在彩色多普勒超声引导下行亚甲蓝定位,对照组采用传统手术方法。所有标本切除后进行病理检查,统计两组切缘情况。从精准性及微创性两方面比较两种方法的手术效果。结果观察组中,3例(5.0%)最大切缘>2 cm,57例(95.0%)最大切缘≤2 cm;对照组中,31例(51.7%)最大切缘>2 cm,29例(48.3%)最大切缘≤2 cm。两组比较差异有统计学意义(P=0.000)。观察组6例(10.0%)患者的手术标本镜下切缘阳性,54例(90.0%)切缘阴性;对照组15例(25.0%)镜下切缘阳性,45例(75.0%)切缘阴性。两组比较差异有统计学意义(P=0.031)。观察组和对照组分别有2例和3例在行二次扩切后切缘仍为阳性,改行乳腺全切手术。结论采用术前彩色多普勒超声引导下亚甲蓝定位肿瘤边界指导乳腺癌保乳手术的方法较常规方法在手术精准性及微创性两方面均有优势。     

The in vivo interaction between flavone acetic acid and hyperthermia

The in vivo interaction between flavone acetic acid (FAA) and hyperthermia was studied in a C3H mammary carcinoma grown in the feet of female CDFl mice and in normal foot skin. FAA was intraperitoneally injected prior to local tissue heating in restrained non-anaesthetized animals. Alone, FAA at doses of 100 mg/kg and above, inhibited tumour growth in a dose-dependent fashion. FAA also enhanced the tumour response to heat, the effect being dependent on both the time interval between the two modalities and the FAA dose, the greatest effect occurring when FAA doses of ≥ 150 mg/kg preceeded heat by 3–48h. These effects of FAA correlated with the drug's ability to decrease tumour blood perfusion measured using the RbCl extraction procedure. Injecting 150 mg/kg FAA 3h before heating (42.7d`C) resulted in a 2–2-fold increase in tumour heat damage, but had little effect on the response of normal foot skin in non-tumour-bearing mice. However, this treatment gave a 20-fold increase in normal tissue damage when the skin experiments were repeated in tumour-bearing animals. These effects in skin occurred in the absence of any blood perfusion changes, but appeared to be associated with FAA-induced TNF-α production.     

Tracer agents for the detection of sentinel lymph nodes in breast cancer: current concerns and directions for the future

Tracer agents play a central role in axillary lymphatic mapping for sentinel node identification during breast cancer surgery. This article reviews the data concerning safety, efficacy, and availability of tracers currently in use. Alternate tracer materials are introduced, with review of the current literature.     

温热顺铂对肝癌细胞的杀伤效应及其诱导凋亡的研究

 目的 探讨温热 ＣＤＤＰ对 Ｈｃａ－Ｆ细胞的生长抑制、温度与药效的关系以及诱导凋亡的作用。方法 采用ＭＴＴ法，透射电镜，ＤＮＡ电泳以及流式细胞术分析法。结果ＣＤＤＰ对Ｈｃａ－Ｆ细胞有明显的细胞毒性，其ＩＣ５０值为０．５７μｇ／ｍｌ。ＣＤＤＰ合并高温（＞４１℃）加热明显提高了ＣＤＤＰ的杀伤力，二者之间存在着协同增敏作用。其作用强度呈现对药物浓度、作用时间与加热温度的正相关性，且在一定浓度范围内以谤导肿瘤细胞凋亡的发生为主。结论 加热（＞４１℃）顺铂提高了顺铂的细胞毒性。诱导细胞凋亡的发生是其抗肿瘤作用的主要机制之一。     

Effects of heat and other agents on amino acid uptake in Escherichia coli

In Escherichia coli K1060 grown at 37°C we observed that the uptake of both L-[³H]leucine and L-[³⁵S]methionine was inhibited by exposure of the cells to 48°C. The calcium channel Mockers diltiazem and verapamil, and the anti-arrhythmic agent quinidine, inhibited the uptake of L-[³H]leucine at both 37°C and 48°C. Verapamil also inhibited the uptake of L-[³⁵S]methionine at 37°C, but at 48°C protected against some of the heat-induced decrease in the uptake of this amino acid. The local anaesthetic procaine markedly inhibited the uptake of both labelled amino acids at temperatures between 37°C and 48°C. Amino acid uptake and cell killing were not correlated.