Influence of different iodinated contrast media on the induction of DNA double‐strand breaks after in vitro X‐ray irradiation

The objective of this work was to examine differences in DNA double‐strand break induction in peripheral blood lymphocytes after in vitro X‐ray irradiation between iodinated contrast agents. Four different iodinated X‐ray contrast agents – three of them with two different iodine concentrations – and mannitol (negative control; concentration of 150 mg mannitol per ml blood) were pipetted into blood samples so that there was a concentration of 0, 7.5 or 15 mg of iodine per ml blood in the samples. Negative controls without contrast medium (0 mg of iodine per ml blood) were also processed for every irradiation dose. The tubes were exposed to 0, 20 or 500 mGy in vitro X‐ray irradiation. After that, the lymphocytes were separated by using density‐gradient centrifugation. Fluorescence microscopy was applied to determine the average number of γH2AX‐foci per lymphocyte in the presence or absence of different contrast media or mannitol. Differences in the number of γH2AX‐foci were statistically analysed by one‐way ANOVA and post‐hoc Tukey's honestly significant difference test. Iodinated contrast agents led to a statistically significant increase in DNA double‐strand breaks after in vitro irradiation. This effect increased statistically significant with rising radiation dose and appeared independent of the contrast agent used (iopromid, iodixanol, iomeprol, iopamidol). A statistically significant difference in DNA damage between the different tested contrast agents was not found. Therefore, the increase in DNA double‐strand breaks depends solely on the amount of iodine applied. For evaluation of clinical consequences, our findings could be tested in further animal studies. Copyright © 2014 John Wiley & Sons, Ltd.     

The presence of iodinated contrast agents amplifies DNA radiation damage in computed tomography

The purpose of this study was to determine the influence of iodinated contrast agents on the formation of DNA double‐strand breaks in vitro in lymphocytes and to verify these results in patients undergoing diagnostic computed tomography examinations. Blood samples were irradiated in vitro in the presence of iodinated X‐ray contrast agent. Controls were irradiated without contrast agent. Fourteen patients were investigated using contrast‐enhanced computed tomography (CT), and 14 other patients with unenhanced CT. Blood samples were taken prior to and 5 min and 1, 2 and 24 h after the CT examination. In these blood samples the average number of γH2Ax‐foci per lymphocyte was enumerated by fluorescence microscopy. Statistical differences between foci numbers developed in the presence and absence of contrast agent were tested using an independent sample t‐test. In vitro foci numbers after irradiation were significantly higher when contrast agent was present during irradiation. In vivo, γH2Ax‐foci levels were 58% higher in patients undergoing contrast‐enhanced CT compared with those undergoing unenhanced CT. In the presence of iodinated contrast agents DNA, damage is increased and the radiation dose is not the only factor affecting the amount of DNA damage. Individual patient characteristics and biological dosimetry applications, e.g. the analysis of γH2Ax‐foci, have to be considered. Copyright © 2011 John Wiley & Sons, Ltd.     

In vivo comparison of tantalum,tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double‐contrast dual‐energy CT of the bowel

To assess the ability of dual‐energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double‐contrast enhanced scans using iodinated intravenous contrast and experimental enteric non‐iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (?100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30–44% and 36–45%, both p < 0.001) higher for double‐contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double‐contrast DECT was scored 29 and 35 percentage points (95% CI 20–35% and 33–39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double‐contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15–31% and 28–33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double‐contrast DECT with iodinated intravenous and either tantalum‐ or tungsten‐based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd.     

Tumor imaging in small animals with a combined micro‐CT/micro‐DSA system using iodinated conventional and blood pool contrast agents

X‐ray based micro‐computed tomography (CT) and micro‐digital subtraction angiography (DSA) are important non‐invasive imaging modalities for following tumorogenesis in small animals. To exploit these imaging capabilities further, the two modalities were combined into a single system to provide both morphological and functional data from the same tumor in a single imaging session. The system is described and examples are given of imaging implanted fibrosarcoma tumors in rats using two types of contrast media: (a) a new generation of blood pool contrast agent containing iodine with a concentration of 130 mg/mL (Fenestra? VC, Alerion Biomedical, San Diego, CA, USA) for micro‐CT and (b) a conventional iodinated contrast agent (Isovue®‐370 mg/mL iodine, trademark of Bracco Diagnostics, Princeton, NJ, USA) for micro‐DSA. With the blood pool contrast agent, the 3D vascular architecture is revealed in exquisite detail at 100 µm resolution. Micro‐DSA images, in perfect registration with the 3D micro‐CT datasets, provide complementary functional information such as mean transit times and relative blood flow through the tumor. This imaging approach could be used to understand tumor angiogenesis better and be the basis for evaluating anti‐angiogenic therapies. Copyright © 2006 John Wiley & Sons Ltd.     

Utilization of nanoparticles as X‐ray contrast agents for diagnostic imaging applications

Among all the diagnostic imaging modalities, X‐ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X‐ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X‐ray imaging. To date, clinically used X‐ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X‐ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X‐rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X‐ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X‐ray contrast agents are discussed and the parameters that influence the efficacy of X‐ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine‐free NP‐based X‐ray contrast agents are then provided, emphasizing the studies performed to evaluate their X‐ray attenuation capabilities and their toxicity in vitro and in vivo. Copyright © 2014 John Wiley & Sons, Ltd.     

Anatomical and functional imaging of myocardial infarction in mice using micro‐CT and eXIA 160 contrast agent

Noninvasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro‐CT cardiac imaging. eXIA 160 creates strong contrast between blood and tissue immediately after its injection and is subsequently taken up by the myocardium and other metabolically active tissues over time. We focus on these properties of eXIA and show its use in imaging myocardial infarction in mice. Five C57BL/6 mice were imaged ~2 weeks after left anterior descending coronary artery ligation. Six C57BL/6 mice were used as controls. Immediately after injection of eXIA 160, an enhancement difference between blood and myocardium of ~340 HU enabled cardiac function estimation via 4D micro‐CT scanning with retrospective gating. Four hours post‐injection, the healthy perfused myocardium had a contrast difference of ~140 HU relative to blood while the infarcted myocardium showed no enhancement. These differences allowed quantification of infarct size via dual‐energy micro‐CT. In vivo micro‐SPECT imaging and ex vivo triphenyl tetrazolium chloride (TTC) staining provided validation for the micro‐CT findings. Root mean squared error of infarct measurements was 2.7% between micro‐CT and SPECT, and 4.7% between micro‐CT and TTC. Thus, micro‐CT with eXIA 160 can be used to provide both morphological and functional data for preclinical studies evaluating myocardial infarction and potential therapies. Further studies are warranted to study the potential use of eXIA 160 as a CT molecular imaging tool for other metabolically active tissues in the mouse. Copyright © 2014 John Wiley & Sons, Ltd.     

Significance and measurement of DNA double strand breaks in mammalian cells.

Techniques for measuring DNA double strand breaks in mammalian cells are being used increasingly by researchers studying both physiological processes, such as recombination, replication, and apoptosis, as well as pathological processes, such as clastogenesis induced by ionizing radiation, chemotherapeutic drugs, and chemical toxicants. In this review we evaluate commonly used assays for measuring DNA double strand breaks, focusing on neutral filter elution and pulsed field gel electrophoresis, and explore the advantages and limitations of applying these techniques to problems of current interest in carcinogenesis and genetic toxicology.     

Development and Evaluation of a CT Pulmonary Angiography Protocol Dedicated to Pregnant and Postpartum Women

IntroductionThis study presents and evaluates a CT pulmonary angiography protocol dedicated to pregnant women. The specific feature of this protocol is to place the region of interest (ROI) (bolus detection) in the superior vena cava. The objective is to evaluate the performances of this method.Materials and methodsThe protocol uses a iodine-based contrast agent at 300mgI/mL and an injection rate of 5 to 6 mL/sec for an injection volume of 50 mL of iodine contrast agent followed by 40 mL of NaCl. The ROI is positioned on the superior vena cava, with a 100 Hounsfield units (HU) threshold, and the acquisition is performed at 100 kVp. This protocol was evaluated retrospectively on a large population (n = 105: group 1) and compared with a control group that did not benefit from this protocol (n = 55: group 2). Both groups were studied on the same device in the same center. Each examination was evaluated and classified into 3 groups: optimal, suboptimal, and noncontributory. Dose length products (DLP) values were also recorded. Statistical tests were applied to the data collected.ResultsThe rate of noncontributory examinations increased from 43.1% for the control group to 4.8% for the new protocol group. The reference enhancement level in the pulmonary trunk is 250 UH. The mean enhancement in the pulmonary trunk of the new protocol group (332 HU (±71 HU (±71 HU)) is significantly greater than the reference value of 250 HU (P < .0001), which is not the case for control group (P = .3485 > .05), which has a mean enhancement of 239 HU (±87 HU). The control group had a mean DLP of 225 mGy.cm (±81 mGy.cm), and the new-protocol group had a mean DLP of 189 mGy.cm (±75 mGy.cm).DiscussionOur noncontributory examination rate is the lowest rate described in the literature. Our protocol contradicts standard practices of placing an ROI in the pulmonary trunk for bolus detection of iodinated contrast media.ConclusionThe results of this study showed that this protocol reduces the number of noncontributory examinations while reducing the dose delivered to patients. This robust protocol is applicable to other devices and meets perfectly radiation-safety requirements and injected contrast media volume limitation.     

BOLD-MRI评价含碘对比剂对糖尿病肾病兔肾脏氧含量的影响

目的 采用BOLD-MRI评价含碘对比剂对糖尿病肾病兔肾脏氧含量的影响。方法 对4组糖尿病肾病实验兔（每组8只）分别注射不同浓度含碘对比剂（200、240、300、350 mgI/ml,命名为200亚组、240亚组、300亚组、350亚组）,对照组（n=8）注射对应剂量生理盐水,注射后1、24、48、72 h进行BOLD-MR检查,测量实验兔肾皮质、外髓和内髓的R2^*值,比较不同组间及时间点间R2^*值的差异。结果 注射对比剂后1 h,各组兔肾皮质、外髓和内髓R2^*值均升高,24 h升至最高,之后开始下降。注射对比剂后各时间点,350亚组、300亚组、240亚组、200亚组与对照组间肾皮质、外髓、内髓的R2^*值总体差异均有统计学意义（P均<0.001）,随碘对比剂浓度增高R2^*值逐渐增高,350亚组R2^*值最高。注射后24 h,350亚组中,肾外髓R2^*值高于皮质和内髓（P均<0.05）。结论 含碘对比剂可明显影响糖尿病肾病实验兔肾脏氧含量,其变化存在一定规律;BOLD-MRI可为临床合理应用对比剂和监测肾功能提供更多辅助信息。     

Functional DNA repair system analysis in haematopoietic progenitor cells using host cell reactivation

in individual DNA repair systems are involved in both de novo and therapy‐related acute myeloid leukaemia (t‐AML), as indicated by genetic markers involving nucleotide excision repair (NER gene polymorphisms), double‐strand‐break (DSB) or mismatch repair (microsatellite instability (MSI)). We modified a host cell reactivation (HCR) assay for functional DNA repair system analysis of living primary haematopoietic cells; 2×10⁵ normal peripheral blood lymphocytes (PBLs) and cord blood CD34+ progenitor cells were cryopreserved, thawed and transfected with 75–250?ng luciferase reporter plasmid (pCMVLuc) using DEAE‐dextran (0.1?mg/mL) in a transfection volume of 250 µL. We obtained luciferase activities of ～300‐fold above background in CD34+ progenitor cells and ～2000‐fold in PBLs, thus rendering these cells applicable for DNA repair analysis. We then evaluated the NER (UV‐irradiated pCMVLuc) and DSB repair capacity (linearized pCMVLuc) of normal lymphocytes and several leukaemic cell lineages. Kasumi‐1 and HL‐60 AML cells exhibited a reduced NER capacity compared to normal GM03715 lymphocytes, PBLs and CD34+ progenitor cells (6.2±0.9%, 6.5±0.9% vs. 12.3±1.8%, 13.5±0.7% and 13.5±2.0%, respectively). Kasumi‐1 AML cells exhibited a reduced DSB repair capacity compared to AG10107 and GM03715 normal lymphocytes as well as CEM acute T‐cell lymphoblastic leukaemia cells (6.4±0.8% vs. 10.8±0.7%, 27.3±1.1% and 20.5±1.6%, respectively). The modified HCR assay can be used for functional DNA repair analysis in living cells of patients with pre‐ and post‐leukaemic conditions as well as in leukaemic blasts to elucidate the role of DNA repair in de novo and t‐AML leukaemogenesis and to determine the individual susceptibility to t‐AML prior to chemotherapy.     

低管电压低碘含量对比剂上腹部增强CT检查

目的 探讨低管电压低碘含量对比剂上腹部增强CT检查的应用价值。方法 选取100例接受上腹部增强CT扫描患者,随机分为A组（管电压120 kVp、碘含量300 mgI/ml）、B组（管电压120 kVp、碘含量270 mgI/ml）、C组（管电压100 kVp、碘含量300 mgI/ml）及D组（管电压100 kVp、碘含量270 mgI/ml）,各25例;均采用40%ASiR算法和FBP算法混合图像重建。测量并分析各组门静脉期图像相同部位CT值、CNR、图像噪声、容积CT剂量指数（CTDIvol）。按4分制对所得图像进行总体图像质量评价,并进行组间比较。分析CT诊断与病理结果的符合率。结果 D组与A组比较,腹主动脉CT值、肝实质CT值、CNR_腹主动脉、CNR_肝实质、噪声差异均无统计学意义（P均>0.05）。A、B、C、D组CTDIvol分别为15.73±5.59、15.34±4.20、12.57±2.55、11.23±2.57,D组与A组比较差异有统计学意义（P<0.05）。4组CT诊断符合率分别为95.45%、90.00%、90.48%、90.91%。4组图像主观评分一致性良好。CT诊断符合率分别为95.45%、90.00%、90.48%、90.91%（P>0.05）。结论 采用低管电压（100 kVp）结合低碘含量（270 mgI/ml）对比剂行上腹部增强CT检查,所得图像质量符合诊断要求,且可降低X线辐射剂量。     

Does iodine concentration affect the diagnostic efficacy of biphasic spiral CT in patients with hepatocellular carcinoma?

Background We investigated the effect of iodinated contrast medium concentration on increased neoplastic lesion enhancement and its direct relation to diagnostic efficacy in biphasic spiral computed tomography for detection of hepatocellular carcinoma.Methods A pilot, single-center, randomized, double-blind, crossover, comparative study was performed and included 22 participants. Each patient underwent two separate biphasic contrast-enhanced spiral computed tomographic examinations. Scans were performed with iomeprol containing 400 (iomeprol 400) or 300 (iomeprol 300) mg of iodine per milliliter (Iomeron, Bracco Imaging SpA, Milan, Italy) with a 2- to 12-day window scan; patients were given an equal total dose of 45 g of iodine at a fixed injection rate of 4 mL/s. Comparison included assessment of quantitative and qualitative parameters.Results Lesion density and lesion-to-liver contrast increased more markedly with the higher concentration of contrast medium during the arterial phase (p = 0.0016 and 0.0005, respectively). There was no significant difference in any parameter between the two concentrations during the portal phase. Number of lesions detected during the arterial phase increased from 37 with iomeprol 300 to 42 with iomeprol 400; in the portal phase, the respective numbers were 34 and 36.Conclusion Even though a small number of patients was examined, our study suggests that, in patients with cirrhosis, an increased concentration of iodine improves liver-to-lesion contrast and may improve the detection of hepatocellular carcinoma.     

The influence of radiation and chemotherapy-related DNA strand breaks on carcinogenesis: an evaluation.

PURPOSE: DNA strand breaks are believed to induce carcinogenesis. This study was conducted to analyze induction and repair of irradiation- and chemotherapy-related strand breaks in vitro. METHODS: Friend Leukemia cells were exposed to irradiation and various chemotherapeutic agents at different doses and concentrations. Occurrence of strand breaks was determined fluorometrically, measuring the rate of DNA unwinding immediately after exposure and 24 hours later. RESULTS: The amount of double-stranded DNA decreased significantly for irradiation, doxorubicin, dactinomycin and etoposide (p < or = 0.05, t-test). After 24 hours free of exposure, the persistent damage was detectable for all of these agents but not for irradiated cells, with DNA strand breaks being decreased for etoposide, unchanged for doxorubicin and increased for methotrexate as well as for dactinomycin. CONCLUSIONS: Severe DNA damage is induced by various chemotherapeutic agents and by irradiation. While repair of chemotherapy-related strand breaks may remain incomplete or prolonged for some chemotherapeutic agents, repair of radiation induced strand breaks is faster and more complete. Therefore chemotherapy-related carcinogenesis may partially be explained by prolonged persistence of DNA strand breaks.     

低管电压与低流速对比剂联合迭代算法在下肢动脉CTA中的应用

目的 探讨低流速对比剂、低电压扫描结合迭代重建算法在下肢动脉CTA检查中的应用价值。方法 收集60例接受双下肢动脉CTA检查者,将其随机分为两组、各30例,实验组:采用低管电压(80 kV)扫描,对比剂注射速率3.3 ml/s,迭代算法重建图像;对照组:采用常规管电压(120 kV),对比剂注射速率5.0 ml/s,使用滤波反投影法进行图像重建。扫描结束后记录容积剂量指数(CTDI)和剂量长度乘积(DLP)。测量腹部至小腿8个ROI及周围肌肉组织的CT值和标准差(图像噪声),计算CNR及SNR,并对图像质量进行评分。比较2组的辐射剂量、碘注射量、血管CT值及图像质量。结果 实验组的CTDI和DLP分别为(3.57±0.64) mGy和(429.26±97.60)mGy·cm,对照组分别为(7.23±0.86)mGy、(918.15±173.53)mGy·cm,二者差异有统计学意义(P均<0.001)。实验组平均碘注射量为(22.49±2.03)g,对照组(33.48±2.97)g,差异有统计学意义(t=2.58,P<0.05)。实验组8个ROI的平均血管CT值和图像噪声均高于对照组,差异有统计学意义(P均<0.05)。两组间CNR、SNR和图像质量主观评分差异无统计学意义(P均>0.05)。结论 采用80 kV管电压、3.3 ml/s对比剂注射速率联合迭代算法行双下肢动脉CTA检查,能够在保证图像质量的同时减少患者所接受的辐射剂量和碘注射量。     

Disruption of redox homeostasis leads to oxidative DNA damage in spermatocytes of Wolbachia-infected Drosophila simulans

Molecular interactions between symbiotic bacteria and their animal hosts are, as yet, poorly understood. The most widespread bacterial endosymbiont, Wolbachia pipientis, occurs in high density in testes of infected Drosophila simulans and causes cytoplasmic incompatibility (CI), a form of male‐derived zygotic lethality. Wolbachia grow and divide within host vacuoles that generate reactive oxygen species (ROS), which in turn stimulate the up‐regulation of antioxidant enzymes. These enzymes appear to protect the host from ROS‐mediated damage, as there is no obvious fitness cost to Drosophila carrying Wolbachia infections. We have now determined that DNA from Wolbachia‐infected mosquito Aedes albopictus (Aa23) cells shows a higher amount of the base 8‐oxo‐deoxyguanosine, a marker of oxidative DNA damage, than DNA from uninfected cells, and that Wolbachia infection in D. simulans is associated with an increase in DNA strand breaks in meiotic spermatocytes. Feeding exogenous antioxidants to male and female D. simulans dramatically increased Wolbachia numbers with no obvious effects on host fitness. These results suggest that ROS‐induced DNA damage in sperm nuclei may contribute to the modification characteristic of CI expression in Wolbachia‐infected males and that Wolbachia density is sensitive to redox balance in these flies.     

Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents

Long circulation time is critical for blood pool contrast agents used in high‐resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long‐circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3‐(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbo‐diimide hydrochloride/N‐hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time. Copyright © 2012 John Wiley & Sons, Ltd.     

Ionizing radiation-induced DNA damage and repair

Ionizing radiation has been shown to induce various types of chromosomal DNA damages. Among these DNA damages, DNA double strand breaks(DSBs) are the most severe damages resulting in cell death or chromosome abnormalities. Proteins associated with DNA repair, such as phosphorylated form of histone H2AX, a histone variant of H2A, and a DNA recombinase RAD51, has been shown to form radiation-induced repair foci at sites containing DNA damage. Reorganization of damaged chromatin by protein modifications or exchange of histones has been shown to play an important role in the formation of radiation induced repair foci.     

对比增强能谱乳腺X线摄影的临床应用及进展

乳腺癌是目前女性发病率最高的恶性肿瘤。早期发现乳腺病变并进行良恶性鉴别，直接影响临床治疗决策，并关系到乳腺癌患者预后。乳腺肿瘤通常血管富集，对比增强能谱乳腺X线摄影（CESM）技术基于碘剂的K边缘效应，通过静脉注射对比剂后对乳腺组织同时进行高、低能量X线摄片，经处理后获得直接反映碘对比剂在腺体内分布情况的减影图像，消除了腺体重叠干扰，显示病灶血供状态，从而可更敏感地发现隐藏于腺体中的小病灶，准确评估病变形态、范围，并进行定性诊断。本文对CESM在乳腺癌临床诊断中的应用和进展进行综述。     

Breast cancer chemotherapy induces the release of cell‐free DNA,a novel procoagulant stimulus

See also van den Berg YW, Reitsma PH. Not exclusively tissue factor: neutrophil extracellular traps provide another link between chemotherapy and thrombosis. This issue, pp 2311–2. Summary. Background: Thrombosis is a common complication for breast cancer patients receiving chemotherapy. However, the mechanisms by which breast cancer chemotherapeutic agents increase this risk are largely uncharacterized. Nucleic acids released by injured cells may enhance coagulation via the activation of the contact pathway. Objectives: In this study, we examined the effects of breast cancer chemotherapy agents on the release of cell‐free DNA (CFDNA) and its relationship to thrombin generation using in vitro and in vivo methods. Methods: CFDNA release and thrombin‐antithrombin (TAT) levels were measured in plasma of breast cancer patients and healthy mice receiving chemotherapy. Venous whole blood and cultured cells were exposed to chemotherapy and CFDNA release and levels of DNA‐histone complexes were measured. The procoagulant activity of isolated CFDNA was measured with calibrated, automated thrombin generation. Results: Breast cancer patients receiving chemotherapy had elevated levels of CFDNA 24 h post‐chemotherapy, a time‐point at which elevated thrombin‐antithrombin levels have been previously reported. Treatment of healthy mice with doxorubicin, epirubicin and 5‐fluorouracil increased CFDNA release, with a corresponding elevation in TAT complex formation. Venous whole blood and neutrophils incubated with chemotherapeutic agents had elevated CFDNA in plasma or cell supernatants. In addition, incubation of venous whole blood with chemotherapy decreased histone‐DNA complex levels. CFDNA released from epirubicin‐treated whole blood significantly elevated thrombin generation in a dose‐dependent manner, and involved activation of the contact pathway. Conclusions: Release of CFDNA from chemotherapy‐injured cells may represent a novel mechanism by which thrombosis is triggered in cancer patients.     

Assessing the effectiveness of X–ray contrast media for abdominal computed tomographic examinations: comparison of four low–osmolality agents

The objective of this investigation was to assess the effectiveness of four iodinated X–ray contrast media for abdominal computed tomographic (CT) examinations. Fifty–three patients were prospectively randomized to receive iohexol 300 mgl/ml (100 ml, n= 17), ioversol 320 mgl/ml (100 ml, n= 13), iopromide 300 mgl/ml (75 ml, n= 12), or iopentol 300 mgl/ml (100 ml, n= 11) to perform a dynamic contrast–enhanced abdominal CT. Imageenhancement profiles for the liver, aorta, and vena cava were studied. The maximum liver enhancement, the time to maximum liver enhancement, and the area under the hepatic enhancement–time curve (AUC) were determined for each examination. Liver–enhancement profile showed significant differences between the four contrast agents, with lower values for iopromide towards the final part of the CT examination (P < 0–05). Hepatic peak values were attained earlier for iopromide, although these were lower than those produced by any other of the agents evaluated in this study. Iopentol produced fast and intense hepatic peaks. Consequently, high AUC values were obtained with iopentol, low values were obtained with iopromide (P < 0–05), although this can be explained by the lower amount of contrast medium contained in the commercial vial and administered to the patient (75 ml vs 100 ml). When normalized to a 100 ml dose, the AUC value for iopromide becomes even higher than the average of the other three agents (P= 0–05). Ioversol, although available and administered as a more concentrated solution (320 mg/ml), was comparable to the less concentrated iohexol and iopentol (300 mgl/ml). In an attempt to measure overall radiographic efficacy, data were normalized per gram of iodine administered. Iopentol and iopromide showed higher liver CT enhancement capacity and lower cost per gram of iodine. We conclude that there are no striking differences in image–enhancing ability of the four contrast media to recommend one over another. Nevertheless, other factors should be considered when selecting a low–osmolality contrast agent, especially iodine content and volume of the commercial formulation, and the cost per gram of iodine.