Saline irrigation for the management of skin extravasation injury in neonates.

PubMed

Gopalakrishnan, P N; Goel, N; Banerjee, Sujoy

2012-02-15

Extravasation injury is a common complication of neonatal intensive care and can result in scarring with cosmetic and functional sequelae. A wide variety of treatments are used in practice including subcutaneous irrigation with saline (with or without hyaluronidase), liposuction, use of specific antidotes, different topical applications and normal wound care with dry or wet dressings. All such treatments aim to prevent or reduce the severity of complications. To determine the efficacy and safety of saline irrigation or saline irrigation with prior hyaluronidase infiltration on tissue healing in neonates with extravasation injury when compared to no intervention or normal wound care. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2), MEDLINE (1950 to June 2011), EMBASE (Jan 1980 to June 2011), CINAHL (Jan 1988 to June 2011) and the Web of Science (up to July 2011). Randomised controlled trials (RCT) and quasi-randomised controlled trials comparing saline irrigation with or without hyaluronidase infiltration with no intervention or normal wound care in the management of extravasation injury in neonates. Three review authors independently reviewed and identified articles for possible inclusion in this review. No eligible studies were found. There were a few case reports and case series describing successful outcomes with different interventions in this condition. To date, no randomised controlled trial is available that examines the effects of saline irrigation with or without prior hyaluronidase infiltration in the management of extravasation injury in neonates. Saline irrigation is a frequently reported intervention in the literature that is used in the management of extravasation injury in neonates. Research should be initially directed at evaluating the efficacy and safety of this intervention through randomised controlled trials. It will also be important to determine the size of the effect according to timing of intervention, nature of the infusate and the severity of injury at the time of intervention.

The effect of four-phasic versus three-phasic contrast media injection protocols on extravasation rate in coronary CT angiography: a randomized controlled trial.

PubMed

Karády, Júlia; Panajotu, Alexisz; Kolossváry, Márton; Szilveszter, Bálint; Jermendy, Ádám L; Bartykowszki, Andrea; Károlyi, Mihály; Celeng, Csilla; Merkely, Béla; Maurovich-Horvat, Pál

2017-11-01

Contrast media (CM) extravasation is a well-known complication of CT angiography (CTA). Our prospective randomized control study aimed to assess whether a four-phasic CM administration protocol reduces the risk of extravasation compared to the routinely used three-phasic protocol in coronary CTA. Patients referred to coronary CTA due to suspected coronary artery disease were included in the study. All patients received 400 mg/ml iomeprol CM injected with dual-syringe automated injector. Patients were randomized into a three-phasic injection-protocol group, with a CM bolus of 85 ml followed by 40 ml of 75%:25% saline/CM mixture and 30 ml saline chaser bolus; and a four-phasic injection-protocol group, with a saline pacer bolus of 10 ml injected at a lower flow rate before the three-phasic protocol. 2,445 consecutive patients were enrolled (mean age 60.6 ± 12.1 years; females 43.6%). Overall rate of extravasation was 0.9% (23/2,445): 1.4% (17/1,229) in the three-phasic group and 0.5% (6/1,216) in the four-phasic group (p = 0.034). Four-phasic CM administration protocol is easy to implement in the clinical routine at no extra cost. The extravasation rate is reduced by 65% with the application of the four-phasic protocol compared to the three-phasic protocol in coronary CTA. • Four-phasic CM injection-protocol reduces extravasation rate by 65% compared to three-phasic. • The saline pacer bolus substantially reduces the risk of CM extravasation. • The implementation of four-phasic injection-protocol is at no cost.

Prevention and Treatment of Heterotopic Ossification

DTIC Science & Technology

2012-02-01

suggest that low oxygen tension critically influences chondrocyte differentiation by accelerating the growth of mesenchymal stem cells and promoting...ossification, we focused on the microenvironmental conditions needed to induce mesenchymal stem cells to differentiate to chondrocytes, which form the...this is due in part to the use of different family members in for extravasating lymphocytes versus mesenchymal stem cells . Since entry of

Dynamic application of microprojection arrays to skin induces circulating protein extravasation for enhanced biomarker capture and detection.

PubMed

Coffey, Jacob W; Meliga, Stefano C; Corrie, Simon R; Kendall, Mark A F

2016-04-01

Surface modified microprojection arrays are a needle-free alternative to capture circulating biomarkers from the skin in vivo for diagnosis. The concentration and turnover of biomarkers in the interstitial fluid, however, may limit the amount of biomarker that can be accessed by microprojection arrays and ultimately their capture efficiency. Here we report that microprojection array insertion induces protein extravasation from blood vessels and increases the concentration of biomarkers in skin, which can synergistically improve biomarker capture. Regions of blood vessels in skin were identified in the upper dermis and subcutaneous tissue by multi-photon microscopy. Insertion of microprojection array designs with varying projection length (40-190 μm), density (5000-20,408 proj.cm(-2)) and array size (4-36 mm(2)) did not affect the degree of extravasation. Furthermore, the location of extravasated protein did not correlate with projection penetration to these highly vascularised regions, suggesting extravasation was not caused by direct puncture of blood vessels. Biomarker extravasation was also induced by dynamic application of flat control surfaces, and varied with the impact velocity, further supporting this conclusion. The extravasated protein distribution correlated well with regions of high mechanical stress generated during insertion, quantified by finite element models. Using this approach to induce extravasation prior to microprojection array-based biomarker capture, anti-influenza IgG was captured within a 2 min application time, demonstrating that extravasation can lead to rapid biomarker sampling and significantly improved microprojection array capture efficiency. These results have broad implications for the development of transdermal devices that deliver to and sample from the skin. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Contrast extravasation on CT angiography predicts hematoma expansion and mortality in acute traumatic subdural hemorrhage.

PubMed

Romero, J M; Kelly, H R; Delgado Almandoz, J E; Hernandez-Siman, J; Passanese, J C; Lev, M H; González, R G

2013-08-01

The presence of active contrast extravasation at CTA predicts hematoma expansion and in-hospital mortality in patients with nontraumatic intracerebral hemorrhage. This study aims to determine the frequency and predictive value of the contrast extravasation in patients with aSDH. We retrospectively reviewed 157 consecutive patients who presented to our emergency department over a 9-year period with aSDH and underwent CTA at admission and a follow-up NCCT within 48 hours. Two experienced readers, blinded to clinical data, reviewed the CTAs to assess for the presence of contrast extravasation. Medical records were reviewed for baseline clinical characteristics and in-hospital mortality. aSDH maximum width in the axial plane was measured on both baseline and follow-up NCCTs, with hematoma expansion defined as >20% increase from baseline. Active contrast extravasation was identified in 30 of 199 discrete aSDHs (15.1%), with excellent interobserver agreement (κ = 0.80; 95% CI, 0.7-0.9). The presence of contrast extravasation indicated a significantly increased risk of hematoma expansion (odds ratio, 4.5; 95% CI, 2.0-10.1; P = .0001) and in-hospital mortality (odds ratio, 7.6; 95% CI, 2.6-22.3; P = 0.0004). In a multivariate analysis controlled for standard risk factors, the presence of contrast extravasation was an independent predictor of aSDH expansion (P = .001) and in-hospital mortality (P = .0003). Contrast extravasation stratifies patients with aSDH into those at high risk and those at low risk of hematoma expansion and in-hospital mortality. This distinction could affect patient treatment, clinical trial selection, and possible surgical intervention.

Large-volume iodinated contrast medium extravasation: low frequency and good outcome after conservative management in a single-centre cohort of more than 67,000 patients.

PubMed

Ko, Chih-Hsiang; Tay, Shee Yen; Chang, Hsiu-Chin; Chan, Wing P

2018-06-12

Our aim was to retrospectively investigate the frequency and outcome of large-volume iodinated contrast medium (CM) extravasation in our institution and to compare our management protocol to current practice. Institutional review board approval was obtained, and informed consent was waived because the study was retrospective. From January 2008 to September 2016, radiological examinations with intravenous non-ionic iodinated CM administration were performed in 67,129 patients. Contrast medium extravasation events on CT scans and intravenous pyelograms but not on angiograms were included. All data were collected prospectively and stratified according to age, injection method (manual vs auto-injection), prevention of extravasation by various means (including intercom alarm), management of extravasation (routine application of silver sulfadiazine ointment, clobetasol propionate cream, and damp gauze at room temperature), etc. RESULTS: The incidence of large-volume CM extravasation was very low (0.04% [27/67,129] overall; 0.03% related to manual injection [age range, 59-92 years; mean, 75.4 years], and 0.045% related to auto-injection [age range, 36-86 years; mean, 65.8 years]). The CM extravasation volume in majority of patients was 20-40 ml in 5 of 9 patients (55.6%) in the manual injection group and 14 of 18 (77.8%) in the auto-injection group. Swelling and pain were the most common symptoms. No patient developed severe signs or needed surgical intervention. Results show a very low incidence of large-volume CM extravasation without severe complications or sequelae. The casual effect between our protocols and good outcome cannot be scrutinised thoroughly because the study lacks a control group and is retrospective. • The incidence of large-volume contrast medium extravasation (≥20 ml) was 0.04%. • No patient needed surgical intervention, and most recovered within 7 days. • Each element of our management protocol contributed to good outcome.

Microvascular perfusion during focal vasogenic brain edema: a scanning laser fluorescence microscopy study.

PubMed

Lindsberg, P J; Sirén, A L; Hallenbeck, J M

1997-01-01

Controversy exists about the effect of tissue edema on cerebral microcirculation. High spatial resolution is required for observation of extravasation and microcirculation during focal vasogenic edema formation. To study the relationship between tissue edema and perfusion, we developed a technique for simultaneous visualization of extravasation and microvessel perfusion in rats. Focal intracortical microvascular injury was generated with a 1-sec Nd-YAG laser pulse. Evans blue albumin (EBA) was infused 30 min before decapitation to study extravasation and FITC-dextran was injected 30 sec prior to decapitation to examine microvessel perfusion. Computerized scanning laser-excited fluorescence microscopy followed by high resolution image analysis permitted quantitative assessment of both parameters on single fresh-frozen brain sections. Studied at 30 min (3.66 +/- 0.15 mm), 2 hr (4.14 +/- 0.08 mm, P < .05), and 8 hr (4.69 +/- 0.18 mm, P < .01) after injury, the diameter of the circular, sharply demarcated zone of EBA-extravasation increased progressively. At 30 min, microvessels at a zone surrounding the area of EBA-extravasation contained 69 +/- 14% (P < .05) more fluorescent FITC-filling than in the control hemisphere, but the density of perfused microvessels was unchanged. At 2 hr, secondary tissue changes had already occurred in a zone surrounding the initial laser lesion. While severe reduction in the density (-76 +/- 13%, P < .05) of perfused microvessels was observed within 400 to 240 microm inside the border of EBA extravasation, perfusion indexes were normal despite the presence of extravasated plasma constituents within 0-80 microm from the border. In a narrow zone (80 microm) outside the border of extravasation, individual microvessels contained 34 +/- 9% (P < .01) less FITC-fluorescence than those in a homologous area of the uninjured contralateral hemisphere. This report demonstrates the feasibility of simultaneous measurement and high-resolution mapping of indices of microvascular perfusion (density, filling) and extravasated plasma constituents in damaged and intact brain areas. In this model, the presence of extravasated plasma constituents the size of proteins did not immediately influence indices of cortical microcirculation. However, microvascular perfusion may be perturbed surrounding such an area of advancing vasogenic edema formation.

Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.

PubMed

Balajthy, Zoltán; Csomós, Krisztián; Vámosi, György; Szántó, Attila; Lanotte, Michel; Fésüs, László

2006-09-15

Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.

The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model.

PubMed

Boussommier-Calleja, A; Atiyas, Y; Haase, K; Headley, M; Lewis, C; Kamm, R D

2018-03-05

Metastasis is the leading cause of cancer-related deaths. Recent developments in cancer immunotherapy have shown exciting therapeutic promise for metastatic patients. While most therapies target T cells, other immune cells, such as monocytes, hold great promise for therapeutic intervention. In our study, we provide primary evidence of direct engagement between human monocytes and tumor cells in a 3D vascularized microfluidic model. We first characterize the novel application of our model to investigate and visualize at high resolution the evolution of monocytes as they migrate from the intravascular to the extravascular micro-environment. We also demonstrate their differentiation into macrophages in our all-human model. Our model replicates physiological differences between different monocyte subsets. In particular, we report that inflammatory, but not patrolling, monocytes rely on actomyosin based motility. Finally, we exploit this platform to study the effect of monocytes, at different stages of their life cycle, on cancer cell extravasation. Our data demonstrates that monocytes can directly reduce cancer cell extravasation in a non-contact dependent manner. In contrast, we see little effect of monocytes on cancer cell extravasation once monocytes transmigrate through the vasculature and are macrophage-like. Taken together, our study brings novel insight into the role of monocytes in cancer cell extravasation, which is an important step in the metastatic cascade. These findings establish our microfluidic platform as a powerful tool to investigate the characteristics and function of monocytes and monocyte-derived macrophages in normal and diseased states. We propose that monocyte-cancer cell interactions could be targeted to potentiate the anti-metastatic effect we observe in vitro, possibly expanding the milieu of immunotherapies available to tame metastasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantifying and correcting for tail vein extravasation in small animal PET scans in cancer research: is there an impact on therapy assessment?

PubMed

Lasnon, Charline; Dugué, Audrey Emmanuelle; Briand, Mélanie; Dutoit, Soizic; Aide, Nicolas

2015-12-01

Tail vein injection under short anesthesia is the most commonly used route for administering radiopharmaceuticals. However, the small caliber of the vein in rodents may lead to tracer extravasation and thereby compromise quantitative accuracy of PET. We aimed to evaluate a method for correction of interstitial radiotracer leakage in the context of pre-clinical therapeutic response assessment. In two separate studies involving 16 nude rats, a model of human ovarian cancer was xenografted and each was treated with a Phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor or used as a control. Tracer injections were performed via the tail vein by a single operator. Two observers qualitatively evaluated the resulting images and if appropriate drew a volume of interest (VOI) over the injection site to record extravasated activities. Uncorrected and corrected tumors' mean standardized uptake value (SUV)mean was computed (corrected injected activity = calibrated activity - decay corrected residual syringe activity - decay corrected tail extravasated activity). Molecular analyses were taken as a gold standard. The frequency and magnitude of extravasation were analyzed, as well as the inter-observer agreement and the impact of the correction method on tumor uptake quantification. Extravasation never exceeded 20 % of the injected dose but occurred in more than 50 % of injections. It was independent of groups of animals and protocol time points with p values of 1.00 and 0.61, respectively, in the first experiment and 0.47 and 0.13, respectively, in the second experiment. There was a good inter-observer agreement for qualitative analysis (kappa = 0.72) and a moderate agreement when using quantitative analysis (ρ c = 0.94). In both experiments, there was significant difference between uncorrected and corrected SUVmean. Despite this significant difference, mean percent differences between uncorrected and corrected SUVmean in the first and the second experiments were -3.61 and -1.78, respectively. Concerning therapy assessment, in both experiments, significant differences in median %SUVmean between control and treated groups were observed over all time points with either uncorrected and corrected data (p < 0.05). Although extravasation is common and can be reproducibly corrected, this is probably not required for validation of response to drugs that induce large SUV changes. However, further studies are required to evaluate the impact of extravasation in situations where less marked metabolic responses are observed or important extravasations occur.

Recombinant neutral endopeptidase attenuates substance P-induced plasma extravasation in the guinea pig skin.

PubMed

Rubinstein, I; Iwamoto, I; Ueki, I F; Borson, D B; Nadel, J A

1990-01-01

To determine whether exogenously administered neutral endopeptidase (NEP; enkephalinase, EC 3.4.24.11) inhibits the substance P-induced increase in vascular permeability in the skin, we examined the effects of recombinant human NEP on plasma extravasation induced by intradermal injection of substance P in guinea pig skin. Injection of substance P (2.5 X 10(-8) M) induced significant plasma extravasation in the skin (53 +/- 4 mm2 of Evans blue extravasation; mean +/- 1 SEM). In vitro incubation of substance P with recombinant human NEP prior to injection prevented the substance P-induced plasma extravasation in the skin in a dose-dependent fashion. Intradermal preinjection of recombinant human NEP partially inhibited plasma extravasation induced by subsequent injection of substance P (52 +/- 9% of the control without NEP). The H1 and H2 histamine antagonists pyrilamine and cimetidine, and a muscarinic antagonist, atropine, had no effects on substance P-induced responses. Two products of substance P degradation by NEP containing the carboxy-terminal portion, substance P7-11 and substance P8-11, were also without effect. These findings suggest that recombinant human NEP can attenuate substance P-induced increases in vascular permeability in guinea pig skin and, therefore, may be useful in treating dermatologic disorders in which abnormal responses to substance P or other neuropeptides cleaved by NEP may occur.

Efficient extravasation of tumor-repopulating cells depends on cell deformability

PubMed Central

Chen, Junjian; Zhou, Wenwen; Jia, Qiong; Chen, Junwei; Zhang, Shuang; Yao, Wenting; Wei, Fuxiang; Zhang, Yuejin; Yang, Fang; Huang, Wei; Zhang, Yao; Zhang, Huafeng; Zhang, Yi; Huang, Bo; Zhang, Zhihong; Jia, Haibo; Wang, Ning

2016-01-01

Cancer metastasis is the most deadly stage in cancer progression. Despite significant efforts over the past decades, it remains elusive why only a very small fraction of cancer cells is able to generate micrometastasis and metastatic colonization. Recently we have shown that tumor-repopulating cells (TRCs), a highly tumorigenic subpopulation of mouse melanoma cells, can be selected by being cultured and grown in 3D soft fibrin gels. Here we show that when injected into the yolk of a 2 day-post-fertilization (dpf) embryo of Tg (fli1:EGFP or kdrl:mCherry) zebrafish, TRCs are much more efficient in surviving and growing at various secondary sites to generate micrometastasis and metastatic colonization than control melanoma cells that are grown on rigid plastic. The metastasis of TRCs is dependent on the presence of Sox2, a self-renewal gene, and silencing Sox2 leads to the inhibition of TRC metastasis. High-resolution of 3D confocal images of the TRCs at the secondary sites show that extravasation and formation of micrometastases by TRCs are more efficient than by the control cells. Remarkably, efficient extravasation of TRCs in vivo and transmigration in vitro are determined by TRC deformability, as a result of low Cdc42 and high Sox2. Our findings suggest that tumor cell deformability is a key factor in controlling extravasation dynamics during metastasis. PMID:26787224

Quantitative analysis applied to contrast medium extravasation by using the computed-tomography number within the region of interest

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Kim, Moon-Jib; Goo, Eun-Hoe; Kim, Sun-Ju; Kim, Kwang; Kwak, Byung-Joon

2014-02-01

The present study was carried out to present a method to analyze extravasation quantitatively by measuring the computed tomography (CT) number after determining the region of interest (ROI) in the CT images obtained from patients suspected of extravasation induced by contrast medium auto-injection. To achieve this, we divided the study subjects into a group of patients who incurred extravasation and a group of patients who underwent routine scans without incurring extravasation. The CT numbers at IV sites were obtained as reference values, and CT numbers at extravasation sites and hepatic portal veins, respectively, were obtained as relative values. Thereupon, the predicted time for extravasation ( T EP ) and the predicted ratio for extravasation ( R EP ) of an extravasation site were obtained and analyzed quantitatively. In the case of extravasation induced by a dual auto-injector, the values of the CT numbers were confirmed to be lower and the extravasation site to be enlarged when compared to the extravasation induced by a single autoinjector. This is because the physiological saline introduced after the injection of the contrast agent diluted the concentration of the extravasated contrast agent. Additionally, the T EP caused by the auto-injector was about 40 seconds, and we could perform a precise quantitative assessment of the site suspected of extravasation. In conclusion, the dual auto-injection method, despite its advantage of reducing the volume of contrast agent and improving the quality of images for patients with good vascular integrity, was judged to be likely to increase the risk of extravasation and aggravate outcomes for patients with poor vascular integrity by enlarging extravasation sites.

Incidence, risk factors and treatment outcomes of extravasation of cytotoxic agents in an outpatient chemotherapy clinic.

PubMed

Sakaida, Emiko; Sekine, Ikuo; Iwasawa, Shunichiro; Kurimoto, Ryota; Uehara, Takashi; Ooka, Yoshihiko; Akanuma, Naoki; Tada, Yuji; Imai, Chiaki; Oku, Tomoko; Takiguchi, Yuichi

2014-02-01

Extravasation, the accidental leakage of an anticancer agent from a vessel into the surrounding tissues, can lead to irreversible local injuries and severe disability. Despite its considerable clinical importance, evidence-based information on extravasation in chemotherapy is lacking. This study characterized the clinical features of extravasation and identified issues to be resolved in current cancer chemotherapy performed in outpatient settings. We retrospectively reviewed the medical charts of patients who received chemotherapy and sustained extravasation in our Outpatient Chemotherapy Clinic from April 2007 to August 2012. Chemotherapy administration and extravasation management procedures were standardized using the in-house chemotherapy guideline. Among 43 557 patients who received chemotherapy, 35 (0.08%) experienced extravasation. The duration between the start of infusion and extravasation was >2 h in 28 (80.0%) patients. The severity of extravasation was Grades 1, 2 and 3 in 28, 2 and 5 patients, respectively-three of whom were associated with port trouble. The contributing factor for extravasation was walking in 11 (31.4%) patients. All extravasations were cured without surgical intervention by management according to our guidelines. The incidence of extravasation is as low as 0.08%, using our in-house chemotherapy guideline. Extravasation from implanted ports tends to be severe.

Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells.

PubMed

Follain, Gautier; Osmani, Naël; Azevedo, Ana Sofia; Allio, Guillaume; Mercier, Luc; Karreman, Matthia A; Solecki, Gergely; Garcia Leòn, Marìa Jesùs; Lefebvre, Olivier; Fekonja, Nina; Hille, Claudia; Chabannes, Vincent; Dollé, Guillaume; Metivet, Thibaut; Hovsepian, François Der; Prudhomme, Christophe; Pichot, Angélique; Paul, Nicodème; Carapito, Raphaël; Bahram, Siamak; Ruthensteiner, Bernhard; Kemmling, André; Siemonsen, Susanne; Schneider, Tanja; Fiehler, Jens; Glatzel, Markus; Winkler, Frank; Schwab, Yannick; Pantel, Klaus; Harlepp, Sébastien; Goetz, Jacky G

2018-04-09

Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. We aim to elucidate the impact of blood flow on the arrest and the extravasation of circulating tumor cells (CTCs) in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in vessels with favorable flow profiles where flow forces control the adhesion efficacy of CTCs to the endothelium. We biophysically identified the threshold values of flow and adhesion forces allowing successful arrest of CTCs. In addition, flow forces fine-tune tumor cell extravasation by impairing the remodeling properties of the endothelium. Importantly, we also observe endothelial remodeling at arrest sites of CTCs in mouse brain capillaries. Finally, we observed that human supratentorial brain metastases preferably develop in areas with low perfusion. These results demonstrate that hemodynamic profiles at metastatic sites regulate key steps of extravasation preceding metastatic outgrowth. Copyright © 2018 Elsevier Inc. All rights reserved.

Injury due to extravasation of thiopental and propofol: Risks/effects of local cooling/warming in rats.

PubMed

Shibata, Yuuka; Yokooji, Tomoharu; Itamura, Ryo; Sagara, Yumeka; Taogoshi, Takanori; Ogawa, Katsunari; Tanaka, Maiko; Hide, Michihiro; Kihira, Kenji; Matsuo, Hiroaki

2016-12-01

Inadvertent leakage of medications with vesicant properties can cause severe necrosis in tissue, which can have devastating long-term consequences. The aim of this study was to evaluate the extent of extravasation injury induced by thiopental and propofol, and the effects of cooling or warming of local tissue on extravasation injury at macroscopic and histopathologic levels. Rats were administered intradermally thiopental (2.5 mg/100 µL) or propofol (1.0 mg/100 µL). Rats were assigned randomly to three groups: control (no treatment), cooling and warming. Local cooling (18-20 °C) or warming (40-42 °C) was applied for 3 h immediately after agent injection. Lesion sizes (erythema, induration, ulceration, necrosis) were monitored after agent injection. Histopathology was evaluated in skin biopsies taken 24 h after agent injection. Thiopental injection induced severe skin injury with necrosis. Peak lesions developed within 24 h and healed gradually 18-27 days after extravasation. Propofol induced inflammation but no ulceration, and lesions healed within 1-2 days. Local cooling reduced thiopental- and propofol-induced extravasation injuries but warming strongly exacerbated the skin lesions (e.g., degeneration, necrosis) induced by extravasation of thiopental and propofol. Thiopental can be classified as a "vesicant" that causes tissue necrosis and propofol can be classified as an "irritant". Local cooling protects (at least in part) against skin disorders induced by thiopental and propofol, whereas warming is harmful.

Incidence, risk factors and treatment outcomes of drug extravasation in pediatric patients in China.

PubMed

Yan, Ya-Min; Gong, Mei; Chen, Jia-Ling; Li, Dan; Xu, Ting-Ting; Zou, Huan; Li, Ai-Qiu; Fan, Qiao-Ling; Lu, Qun-Feng

2017-01-01

Yan YM, Gong M, Chen JL, Li D, Xu TT, Zou H, Li AQ, Fan QL, Lu QF. Incidence, risk factors and treatment outcomes of drug extravasation in pediatric patients in China. Turk J Pediatr 2017; 59: 162-168. Extravasation injury is a common phenomenon in hospitals. Failure to detect and treat extravasation injury can lead to irreversible local injuries, tissue necrosis and malfunction of the affected tissue. Until now, it is largely unknown about incidence, risk factors and treatment outcomes of extravasation in Chinese pediatric patients. The aim of this study is to explore the incidence, risk factors and summarize the characteristics and treatment outcomes of extravasation injuries resulting in drug extravasation among Chinese children in our hospital. The children undergoing infusion therapy (0-18 years) were enrolled in this study between December 2014 and June 2015 in Shanghai Children`s Hospital. The patients` information including age, gender, injection site, estimated volume of solution extravasated, patient symptoms, severity of extravasation injury, treatment methods, and outcomes was collected. Multivariate logistic regression was used to identify the independent risk factors for the development of extravasation. The incidence of extravasations in pediatric patients was 1.79% (18/1,004). The severity of extravasation was labeled with grade range from Grade 1 through Grade 4: 4 cases with Grade 1, 8 cases with Grade 2, 5 cases with Grade 3, and 1 case with Grade 4. The risk factors of extravasation include infused high volume/day (≥1000 ml), received operation, infused agents with high osmolarity and poor vein condition. The severity of extravasation was related to the large volumes of drug or special drugs (high-osmolarity, high-risk, low pH, etc). All extravasations were treated with physical, pharmacological and surgical intervention according to our standard operation protocols. Systematic implementation of intervention can alleviate the extravasation injuries and improve the patients` outcome.

Management of extravasation injuries: a focused evaluation of noncytotoxic medications.

PubMed

Reynolds, Paul M; MacLaren, Robert; Mueller, Scott W; Fish, Douglas N; Kiser, Tyree H

2014-06-01

Extravasations are common manifestations of iatrogenic injury that occur in patients requiring intravenous delivery of known vesicants. These injuries can contribute substantially to patient morbidity, cost of therapy, and length of stay. Many different mechanisms are behind the tissue damage during extravasation injuries. In general, extravasations consist of four different subtypes of tissue injury: vasoconstriction, osmotic, pH related, and cytotoxic. Recognition of high-risk patients, appropriate cannulation technique, and monitoring of higher risk materials remain the standard of care for the prevention of extravasation injury. Prompt interdisciplinary action is often necessary for the treatment of extravasation injuries. Knowledge of the mechanism of extravasation-induced tissue injury, agents for reversal, and appropriate nonpharmacologic treatment methods is essential. The best therapeutic agent for treatment of vasopressor extravasation is intradermal phentolamine. Topical vasodilators and intradermal terbutaline may provide relief. Intradermal hyaluronidase has been effective for hyperosmotic extravasations, although its use largely depends on the risk of tissue injury and the severity of extravasation. Among the hyperosmotic agents, calcium extravasation is distinctive because it may present as an acute tissue injury or may possess delayed clinical manifestations. Extravasation of acidic or basic materials can produce significant tissue damage. Phenytoin is the prototypical basic drug that causes a clinical manifestation known as purple glove syndrome (PGS). This syndrome is largely managed through preventive and conservative treatment measures. Promethazine is acidic and can cause a devastating extravasation, particularly if administered inadvertently through the arteriolar route. Systemic heparin therapy remains the accepted treatment option for intraarteriolar administration of promethazine. Overall, the evidence for managing extravasations due to noncytotoxic medications is nonexistent or limited to case reports. More research is needed to improve knowledge of patient risk, prompt recognition of the extravasation, and time course for tissue injury, and to develop prevention and treatment strategies for extravasation injuries. © 2014 Pharmacotherapy Publications, Inc.

Intravenous contrast extravasation during CT: a national data registry and practice quality improvement initiative.

PubMed

Dykes, Thomas M; Bhargavan-Chatfield, Mythreyi; Dyer, Raymond B

2015-02-01

Establish 3 performance benchmarks for intravenous contrast extravasation during CT examinations: extravasation frequency, distribution of extravasation volumes, and severity of injury. Evaluate the effectiveness of implementing practice quality improvement (PQI) methodology in improving performance for these 3 benchmarks. The Society of Abdominal Radiology and ACR developed a registry collecting data for contrast extravasation events. The project includes a PQI initiative allowing for process improvement. As of December 2013, a total of 58 radiology practices have participated in this project, and 32 practices have completed the 2-cycle PQI. There were a total of 454,497 contrast-enhanced CT exams and 1,085 extravasation events. The average extravasation rate is 0.24%. The median extravasation rate is 0.21%. Most extravasations (82.9%) were between 10 mL and 99 mL. The majority of injuries, 94.6%, are mild in severity, with 4.7% having moderate and 0.8% having severe injuries. Data from practices that completed the PQI process showed a change in the average extravasation rate from 0.28% in the first 6 months to 0.23% in the second 6 months, and the median extravasation rate dropped from 0.25% to 0.16%, neither statistically significant. The distribution of extravasation volumes and the severity of injury did not change between the first and second measurement periods. National performance benchmarks for contrast extravasation rate, distribution of volumes of extravasate, and distribution of severity of injury are established through this multi-institutional practice registry. The application of PQI failed to have a statistically significant positive impact on any of the 3 benchmarks. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Extravasation management: clinical update.

PubMed

Schulmeister, Lisa

2011-02-01

To present a clinical update on the prevention, detection, and evidence-based management of vesicant chemotherapy extravasations. Journal articles, published and unpublished case reports, personal experience. In the 4 years that have elapsed since the publication of the original article, much more is known about vesicant chemotherapy extravasation, and effective evidence-based treatments now are available. The antidotes sodium thiosulfate for mechlorethamine extravasations and hyaluronidase for plant alkaloid extravasations are recommended by the manufacturers of these vesicants and cited in nursing guidelines. The anthracycline extravasation treatment dexrazoxane for injection, the first and only extravasation treatment with proven effectiveness, is now available as Totect (dexrazoxane; TopoTarget USA, Rockaway, NJ, USA) in the US and Savene (SpePharm, Amsterdam, The Netherlands) in Europe. Nurses who administer vesicant chemotherapy agents need to be aware of the most current evidence (or lack of evidence) for various types of extravasation treatment. Well-informed nurses are patient advocates and instrumental in detecting, managing, and documenting extravasations. Most importantly, nurses play a key role in preventing vesicant chemotherapy extravasations. Copyright © 2011 Elsevier Inc. All rights reserved.

Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves

DTIC Science & Technology

2014-12-01

developed in Ova -sensitized mice was less pronounced in TRPV1-null mice, indicating an important role of TRPV1. 2) An increase in airway temperature...actively sensitized by inhalation of ovalbumin ( Ova ) aerosol for 3 weeks). These rats were divided into two groups: control and sensitized groups...airway extravasation in Ova -sensitized rats. 2) The airway 5 extravasation can be prevented by pretreatment with the selective antagonist of NK-1

Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review.

PubMed

van der Pol, Jochem; Vöö, Stefan; Bucerius, Jan; Mottaghy, Felix M

2017-07-01

Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents. A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords "misadministration", "extravasation", "paravascular infiltration", combined with "tracer", "radionuclide", "radiopharmaceutical", and a list of keywords referring to clinically used tracers (i.e. "Technetium-99m", "Yttrium-90"). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised. Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature. Extravasation of diagnostic radiopharmaceuticals is common. 99m Tc, 123 I, 18 F, and 68 Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation.

[Extravasation of contrast media at the puncture site: Strategies for managment].

PubMed

Pacheco Compaña, F J; Gago Vidal, B; Méndez Díaz, C

2014-01-01

The incidence of contrast medium extravasation at the venipuncture site has increased with the generalized use of automatic injectors. Most extravasations only cause slight edema and erythema. Nevertheless, in some cases extravasation can result in severe skin lesions or even in compartment syndrome. Lesions caused by extravasation usually resolve spontaneously with conservative treatment. Although the complications of extravasation are well known, institutional protocols are normally lacking and the criteria for taking action and the type of treatment, whether based on the literature or personal preferences, tend to vary. In this article, we review the incidence, risk factors, clinical manifestations, and options for preventing and treating contrast medium extravasation in soft tissues. Finally, we present the protocol we use to manage extravasation at our hospital. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

Salivary gland diseases: infections, sialolithiasis and mucoceles.

PubMed

Delli, Konstantina; Spijkervet, Fred K L; Vissink, Arjan

2014-01-01

The three most frequently diagnosed salivary gland diseases are salivary gland infections, sialolithiasis and mucoceles. Salivary gland infections are usually of bacterial or viral etiology and can be divided into acute and chronic types. Occasionally they can result from obstruction of the salivary duct, an autoimmmune disease or cancer therapy. Infections can occur in all types of salivary glands and are observed at all ages. Sialolithiasis is characterized by the development of calcified structures in the salivary glands, especially in the submandibular gland. Sialoliths are generally attributed to retention of saliva and are usually accompanied by swelling and pain when a salivary stimulus is applied. Mucoceles can be differentiated into mucus extravasation phenomenon or mucus escape reaction, mucus retention cysts and ranulas. They result from extravasation of saliva into the surrounding soft tissues or from retention of saliva within the duct.

Management of cytotoxic extravasation - ASORS expert opinion for diagnosis, prevention and treatment.

PubMed

de Wit, Maike; Ortner, Petra; Lipp, Hans-Peter; Sehouli, Jalid; Untch, Michael; Ruhnke, Markus; Mayer-Steinacker, Regine; Bokemeyer, Carsten; Jordan, Karin

2013-01-01

Cytotoxic extravasation is a rare but potentially serious and painful complication of intravenous drug administration in oncology. Literature is anecdotal, and systematic clinical trials are scarce. The German working group for Supportive Care in Cancer (ASORS) has prepared an expert opinion for the diagnosis, prophylaxis and management of cytotoxic extravasation based on an interdisciplinary expert panel. A Pubmed search was conducted for diagnosis, risk factors, symptoms, prophylaxis, and treatment of extravasation by the respective responsible expert. A writing committee compiled the manuscript and proposed the level of recommendation. In a consensus meeting, 13 experts reviewed and discussed the current practice in diagnosis and management of cytotoxic extravasation. In a telephone voting among the experts, the level of recommendation by ASORS was determined. Every effort should be made to reduce the risk of extravasation. Staff training, patient education, usage of right materials and infusion techniques have been identified to be mandatory to minimalize the risk of extravasation. Extravasation must be diagnosed as soon as possible, and specific therapy including antidotes dependent on the extravasated drug should be initiated immediately. An extravasation emergency set should be available wherever intravenous cytotoxics are applied. Documentation and post-treatment follow-up are recommended. We have developed a literature- and expert-based consensus recommendation to avoid cytotoxic extravasation. It also provides practical management instructions which should help to avoid surgery and serious late effects. Copyright © 2013 S. Karger AG, Basel.

Ozone Ameliorates Doxorubicine-Induced Skin Necrosis - results from an animal model.

PubMed

Kesik, Vural; Yuksel, Ramazan; Yigit, Nuri; Saldir, Mehmet; Karabacak, Ercan; Erdem, Galip; Babacan, Oguzhan; Gulgun, Mustafa; Korkmazer, Nadir; Bayrak, Ziya

2016-09-01

Doxorubicin (DXR) extravasation result with serious morbidity like skin ulceration and necrosis. The purpose of this study is to determine the protective effects of ozone, olive oil, dimethyl sulfoxide (DMSO), and coenzyme Q10 in the treatment of DXR-induced skin ulcers on rats. After an intradermal injection of DXR on a basis of an animal extravasation model, the materials were topically applied. The ulcer sizes were measured, and a punch biopsy was taken from the extravasation site in which the skin ulcers formed at the end of the experiment. The samples were analyzed for tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL1β), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzymes, and examined histopathologically. The ulcer sizes clearly decreased in the study groups, including DMSO, olive oil, ozone plus coenzyme Q10, and ozone plus olive oil groups in comparison with the control group with the exception of the coenzyme Q10 group. The malondialdehyde levels were lower in the DMSO, olive oil, ozone plus olive oil, and ozone plus coenzyme Q10 groups than they were in the control group, but they were not significantly different. The TNF-α level was lower in the DMSO, ozone plus olive oil, coenzyme Q10, and ozone plus coenzyme Q10 groups in comparison with the control group. There was no significant change in the SOD, GSH-Px, and IL1β levels in the study groups in comparison with the control and the sham groups. The ozone plus olive oil group could be considered to be an alternate therapy for skin ulcers due to DXR extravasation. © The Author(s) 2015.

Cold-induced fluid extravasation during cardiopulmonary bypass in piglets can be counteracted by use of iso-oncotic prime.

PubMed

Farstad, Marit; Kvalheim, Venny Lise; Husby, Paul

2005-08-01

Hypothermic cardiopulmonary bypass is associated with increased fluid extravasation. This study aimed to compare whether iso-oncotic priming solutions, in contrast to crystalloids, could reduce the cold-induced fluid extravasation during cardiopulmonary bypass in piglets. Three groups were studied: the control group (CT group; n = 10), the albumin group (Alb group; n = 7), and the hydroxyethyl starch group (HES group; n = 7). Prime (1000 mL) and supplemental fluid were acetated Ringer solution, 4% albumin, and 6% hydroxyethyl starch, respectively. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (cooling to 28 degrees C within 15 minutes) was initiated and continued to 90 minutes. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit levels, and tissue water content were recorded, and protein masses and fluid extravasation rates were calculated. Colloid osmotic pressure in plasma decreased immediately after the start of cardiopulmonary bypass in the CT group but remained stable in the Alb and HES groups. Colloid osmotic pressure in interstitial fluid tended to decrease in the CT group and remained unchanged in the Alb group, whereas a slight increase was observed in the HES group. Immediately after the start of cooling, fluid extravasation rates increased from 0.15 +/- 0.10 to 0.64 +/- 0.12 mL . kg -1 . min -1 in the CT group, whereas no such increase was observed in the Alb and HES groups. The changes in fluid extravasation rates were reflected by corresponding changes in tissue water content. The use of albumin or hydroxyethyl starch as prime to preserve the colloid osmotic pressure during cardiopulmonary bypass causes a reduction in the cold-induced fluid extravasation compared with that seen with crystalloids. Albumin seems more effective than hydroxyethyl starch to limit cold-induced fluid shifts during cardiopulmonary bypass.

Cutaneous manifestations of phosphate solution extravasation.

PubMed

Verykiou, S; Aljefri, K; Gopee, H; Taheri, L; Charlton, F; Langtry, J A; Blasdale, C

2018-01-01

Extravasation injuries are common in patients receiving multiple intravenous infusions. Although such injuries are closely associated with the infusion of cytotoxic chemotherapy, they have also been been associated with extravasation of noncytotoxic drugs. Extravasation injuries can lead to skin ulceration and nerve and tendon damage, and therefore to permanent disability. We report three cases of phosphate solution extravasation leading to unusual cutaneous manifestations. © 2017 British Association of Dermatologists.

Incidence of urinary extravasation and rate of ureteral stenting after high-grade renal trauma in adults: a meta-analysis

PubMed Central

Anderson, Ross E.; Fiander, Michelle; McFarland, Mary M.; Stoddard, Gregory J.; Hotaling, James M.; Myers, Jeremy B.

2018-01-01

Background Collecting system injury and urinary extravasation is an important yet understudied aspect of renal trauma. We aimed to examine the incidence of urinary extravasation and also the rates of ureteral stenting after high-grade renal trauma (HGRT) in adults. Methods A search strategy was developed to search Ovid Medline, Embase, CINAHL, and Cochrane Library. Two reviewers screened titles and abstracts, followed by full-text review of the relevant publications. Studies were included if they indicated the number of patients with HGRT [the American Association for the Surgery of Trauma (AAST) grades III–IV or equivalents] and number of patients with urinary extravasation. A descriptive meta-analysis of binary proportions was performed with random-effects model to calculate the incidence of urinary extravasation and rates of ureteral stenting. Results After screening, 24 and 20 studies were included for calculating urinary extravasation and stenting rates, respectively. Most studies involved blunt injury and were retrospective single-center case series. Incidence of urinary extravasation was 29% (95% CI: 17–42%) after HGRT (grade III–V), and 51% (95% CI: 38–64%) when only grade IV–V injuries were combined. Overall, 29% (95% CI: 22–36%) of patients with urinary extravasation underwent ureteral stenting. Conclusions Approximately 30% of patients with HGRT are diagnosed with urinary extravasation and 29% of those with urinary extravasation undergo ureteral stenting. Understanding the rate of urinary extravasation and interventions is the first step in creating a prospective trial designed to demonstrate when ureteral stenting and aggressive management of urinary extravasation is needed. PMID:29928614

Incidence of urinary extravasation and rate of ureteral stenting after high-grade renal trauma in adults: a meta-analysis.

PubMed

Keihani, Sorena; Anderson, Ross E; Fiander, Michelle; McFarland, Mary M; Stoddard, Gregory J; Hotaling, James M; Myers, Jeremy B

2018-05-01

Collecting system injury and urinary extravasation is an important yet understudied aspect of renal trauma. We aimed to examine the incidence of urinary extravasation and also the rates of ureteral stenting after high-grade renal trauma (HGRT) in adults. A search strategy was developed to search Ovid Medline, Embase, CINAHL, and Cochrane Library. Two reviewers screened titles and abstracts, followed by full-text review of the relevant publications. Studies were included if they indicated the number of patients with HGRT [the American Association for the Surgery of Trauma (AAST) grades III-IV or equivalents] and number of patients with urinary extravasation. A descriptive meta-analysis of binary proportions was performed with random-effects model to calculate the incidence of urinary extravasation and rates of ureteral stenting. After screening, 24 and 20 studies were included for calculating urinary extravasation and stenting rates, respectively. Most studies involved blunt injury and were retrospective single-center case series. Incidence of urinary extravasation was 29% (95% CI: 17-42%) after HGRT (grade III-V), and 51% (95% CI: 38-64%) when only grade IV-V injuries were combined. Overall, 29% (95% CI: 22-36%) of patients with urinary extravasation underwent ureteral stenting. Approximately 30% of patients with HGRT are diagnosed with urinary extravasation and 29% of those with urinary extravasation undergo ureteral stenting. Understanding the rate of urinary extravasation and interventions is the first step in creating a prospective trial designed to demonstrate when ureteral stenting and aggressive management of urinary extravasation is needed.

Chemotherapy Extravasation: Establishing a National Benchmark for Incidence Among Cancer Centers.

PubMed

Jackson-Rose, Jeannette; Del Monte, Judith; Groman, Adrienne; Dial, Linda S; Atwell, Leah; Graham, Judy; O'Neil Semler, Rosemary; O'Sullivan, Maryellen; Truini-Pittman, Lisa; Cunningham, Terri A; Roman-Fischetti, Lisa; Costantinou, Eileen; Rimkus, Chris; Banavage, Adrienne J; Dietz, Barbara; Colussi, Carol J; Catania, Kimberly; Wasko, Michelle; Schreffler, Kevin A; West, Colleen; Siefert, Mary Lou; Rice, Robert David

2017-08-01

Given the high-risk nature and nurse sensitivity of chemotherapy infusion and extravasation prevention, as well as the absence of an industry benchmark, a group of nurses studied oncology-specific nursing-sensitive indicators. 
. The purpose was to establish a benchmark for the incidence of chemotherapy extravasation with vesicants, irritants, and irritants with vesicant potential.
. Infusions with actual or suspected extravasations of vesicant and irritant chemotherapies were evaluated. Extravasation events were reviewed by type of agent, occurrence by drug category, route of administration, level of harm, follow-up, and patient referrals to surgical consultation.
. A total of 739,812 infusions were evaluated, with 673 extravasation events identified. Incidence for all extravasation events was 0.09%.

Effect of (18)F-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses.

PubMed

Lee, Jong Jin; Chung, Jin Hwa; Kim, Seog-Young

2016-10-01

The present study aimed to investigate the effect of (18)F-fluorodeoxyglucose (FDG) extravasation on the time taken for tumoral uptake to reach a plateau. For the animal experiment, FDG extravasation was conducted in the tails of HCT116 tumor-bearing xenograft mice models in three groups (no extravasation, 40 % extravasation, and 80 % extravasation; n = 5, each). Dynamic positron emission tomography (PET) images were acquired over a period of 2 h following injection. Time-activity curves for FDG in the tails and tumors were calculated. For the clinical experiment, 22 patients (male:female, 14:8; age range, 70.8 ± 9.2 years) were subjected to PET/computed tomography (PET/CT) 1 h after the injection of FDG. The inclusion criteria were as follows: (1) submitted to both whole-body and subsequent regional scanning; (2) entire extravasation activity visualized in the whole-body images; (3) tumor visualized on both whole-body and additional regional images; and (4) status of tumor either confirmed by biopsy or clinically suspected for malignancy. The standardized uptake values (SUVs) of the tumors (on the whole-body and additional PET images) and extravasation sites were recorded. There were no significant differences in the time taken for tumoral uptake to reach a plateau and that to reach minimum activity at the extravasation site among the three groups of mice. However, the mean tumoral activity and activity at the extravasation site were negatively correlated at 1 h post-injection. According to the clinical PET findings, the differences in SUV between the whole-body and regional images were not significantly correlated with the interval between injection of FDG and start of whole-body scanning, interval between the start of whole-body scanning and start of regional scanning, extravasation volume, maximum SUV of the extravasation site, or total activity at the extravasation site. The time taken for tumoral uptake to reach a plateau is not affected by extravasation, even at extensive degrees. Thus, in routine practice, the imaging time of approximately 60 min post-injection need not be modified even if extravasation is identified. However, tumor SUV may be underestimated in cases of extravasation.

Infiltration and extravasation in pediatric patients: A prevalence study in a children's hospital.

PubMed

Özalp Gerçeker, Gülçin; Kahraman, Ayşe; Yardimci, Figen; Bilsin, Elif; Binay, Şeyda; Çevik Özdemir, Hamide Nur; Karakul, Atiye; Zengin, Dilek; Ardahan Sevgili, Seda; Gümüş, Merve; Başbakkal, Zümrüt; Akpınar, Selma

2018-05-01

The aim of this study is to determine the prevalence of infiltration and extravasation among children staying in a children's hospital and the interventions carried out when infiltration or extravasation occurred. A prospective and descriptive research design was used in the study, conducted between September 2015 and February 2016, and determined the prevalence of infiltration and extravasation and their characteristics. The study sample consisted of 297 peripheral catheters in 173 pediatric patients. Of 297 peripheral catheters, 50.8% were located on the right and 30.6% were inserted in the dorsal metacarpal vein. Infiltration and extravasation occurred in 2.9% and 2.3% of the patients, respectively. The prevalence of infiltration and extravasation was 5.5 and 4.4 per 1000 patient-days, respectively. The applied interventions after infiltration or extravasation included covering with a gauze dressing or alcohol-soaked cotton, cold application, irrigation with physiological saline, and elevation. The infiltration and extravasation prevalence were found to be high, but the interventions to address them were inadequate. Training and implementation strategies should be planned for pediatric nurses to prevent infiltration and extravasation.

Hemoglobin extravasation in the brain of rats exchange-transfused with hemoglobin-based oxygen carriers.

PubMed

Terraneo, Laura; Bianciardi, Paola; Malavalli, Ashok; Mkrtchyan, Gnel; Spann, Stephanie N; Lohman, Jeff; Samaja, Michele; Vandegriff, Kim D

2017-06-01

Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or αα-cross-linked Hb. Animals were sacrificed 2 h after transfusion, brain tissue was harvested and processed for double-staining immunofluorescence, whereby Hb ? chain and NeuN (a neuron protein) were stained and quantitated. Whereas Hextend did not induce Hb extravasation, in both MP4OX and ??Hb brains Hb molecules were detected outside neurons. The level of extravasated Hb chains was > 3-fold higher in Hb compared to MP4OX. Western blot analysis revealed that the expression levels of protein related to redox imbalance (e.g., Nrf2, iNOS and ERK phosphorylation) were higher in ααHb than MP4OX. In conclusions, higher Hb extravasation in ααHb than MP4OX induces redox imbalance, which causes higher anti-oxidant response. Whereas Nrf2 response may be considered protective, iNOS response appears damaging.

Radiofrequency-activated PMMA-augmentation through cannulated pedicle screws: A cadaver study to determine the biomechanical benefits in the osteoporotic spine.

PubMed

Karius, T; Deborre, C; Wirtz, D C; Burger, C; Prescher, A; Fölsch, A; Kabir, K; Pflugmacher, R; Goost, H

2017-01-01

PMMA-augmentation of pedicle screws strengthens the bone-screw-interface reducing cut-out risk. Injection of fluid cement bears a higher risk of extravasation, with difficulty of application because of inconsistent viscosity and limited injection time. To test a new method of cement augmentation of pedicle screws using radiofrequency-activated PMMA, which is suspected to be easier to apply and have less extravasations. Twenty-seven fresh-frozen human cadaver lumbar spines were divided into 18 osteoporotic (BMD ≤ 0.8 g/cm2) and 9 non-osteoporotic (BMD > 0.8 g/cm2) vertebral bodies. Bipedicular cannulated pedicle screws were implanted into the vertebral bodies; right screws were augmented with ultra-high viscosity PMMA, whereas un-cemented left pedicle screws served as negative controls. Cement distribution was controlled with fluoroscopy and CT scans. Axial pullout forces of the screws were measured with a material testing machine, and results were analyzed statistically. Fluoroscopy and CT scans showed that in all cases an adequately big cement depot with homogenous form and no signs of extravasation was injected. Pullout forces showed significant differences (p < 0.001) between the augmented and non-augmented pedicle screws for bone densities below 0.8 g/cm2 (661.9 N ± 439) and over 0.8 g/cm2 (744.9 N ± 415). Pullout-forces were significantly increased in osteoporotic as well as in non-osteoporotic vertebral bodies without a significant difference between these groups using this standardized, simple procedure with increased control and less complications like extravasation.

Dexrazoxane treatment of doxorubicin extravasation injury in four dogs.

PubMed

Venable, Rachel O; Saba, Corey F; Endicott, Melissa M; Northrup, Nicole C

2012-02-01

4 dogs were treated with dexrazoxane for known or suspected doxorubicin extravasation. Records were retrospectively reviewed. Doses and number of doses of dexrazoxane were variable. Dexrazoxane was administered within 2 hours after known extravasation in 3 dogs and 48 hours after suspected extravasation in 1 dog. Additional medical treatments included tissue cooling in all dogs, topically administered dimethyl sulfoxide ointment in 3, and orally administered piroxicam in 1. Mild erythema and edema at the extravasation site developed within 1 to 6 days after extravasation in the 3 dogs that received dexrazoxane within 2 hours after extravasation. Extensive tissue necrosis occurred in the dog treated 48 hours after suspected extravasation. Only the dog with severe tissue necrosis required surgical intervention. Lesions in the other 3 dogs resolved with medical management alone. All dogs survived the event. To date, use of dexrazoxane in the management of doxorubicin extravasation has not been reported in dogs. Treatment was successful in 3 of 4 patients. The most effective dosage and timing of administration are unknown; however, there is evidence to suggest that administration within 6 hours after the event is warranted. Further studies are needed to confirm efficacy and to optimize use of this drug in the prevention and treatment of anthracycline extravasation injury in veterinary patients.

[Extravasation of chemotherapeutic agents: prevention and therapy].

PubMed

Jordan, K; Grothe, W; Schmoll, H-J

2005-01-07

Based on the potential to cause local tissue injury drugs are classified as vesicant, irritant and non-irritant. The frequency of extravasation is considered to be between 0.6 % and 6 %. More frequently an inflammatory reaction is caused by thrombophlebitis or a local hypersensitivity reaction following chemotherapy administration rather than by an extravasation. A number of factors are known to increase the risk of extravasation. By the consideration of these risk factors preventive guidelines for the safe administration of chemotherapeutic agents have been published. Central venous devices significantly reduce the risk of extravasation. To date there are no generally approved treatment guidelines for the management of extravasations. Treatment is mostly empirical. Nevertheless some general measures are to be recommended: Firstly, aspiration of the extravasated fluids should be attempted. Furthermore local supportive care such as intermittent topical warming or cooling is at least palliative and to a certain degree reduces the extent of the injury. Beside these non pharmacological therapies the beneficial effects of Dimethylsulfoxid (DMSO) -- or Hyaluronidase-administration dependent on the type of paravasation have been proven. The use of sodium bicarbonate, sodium thiosulfate or corticosteroids is no longer recommended. In the case of extravasation rapid and correct management is crucial for the benefit of any treatment. Therefore, written guidelines for both the handling of cytotoxic agents and also the management of an extravasation should be present in all Departments where cytotoxic agents are administered. In addition to these guidelines an extravasation kit including all necessary materials and drugs to treat extravasations should be available.

The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat.

PubMed

Sulpizio, Anthony C; Pullen, Mark A; Edwards, Richard M; Brooks, David P

2004-06-01

The effect of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) inhibition on microvascular plasma leakage (extravasation) was evaluated in a rat model. Progressive inhibition of ACE using captopril caused increased extravasation when lung ACE was inhibited by >55%. In contrast, the selective inhibition of renal NEP by >90% using ecadotril did not increase extravasation. In NEP-inhibited rats, extravasation produced by the ACE inhibitors captopril and lisinopril was markedly enhanced. The dual ACE and NEP inhibitor omapatrilat, at oral doses of 0.03, 0.1, and 0.3 mg/kg, selectively inhibited lung ACE by 19, 61, and 76%, respectively, and did not cause significant extravasation. Doses of 1 and 10 mg/kg omapatrilat, which produced >90% inhibition of ACE and also inhibited renal NEP by 54 and 78%, respectively, significantly increased extravasation. In this model, bradykinin and substance P produced extravasation that could be abolished by the bradykinin 2 (B2) receptor antagonist Hoe 140 (icatibant) or the neurokinin1 (NK1) antagonist CP99994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine], respectively. Bradykinin induced extravasation was also partially ( approximately 40%) inhibited by CP99994, indicating that a portion of the response involves B2 receptor-mediated release of substance P. In conclusion, this study is the first to relate the degree of ACE and/or NEP inhibition to extravasation liability in the rat model. Our data clearly demonstrate that ACE inhibitor-induced plasma extravasation is enhanced by concomitant inhibition of NEP. In addition, this study provides further evidence for the role for B2 and NK1 receptors in mediating plasma extravasation in the rat.

Vesicant extravasation part I: Mechanisms, pathogenesis, and nursing care to reduce risk.

PubMed

Sauerland, Carmel; Engelking, Constance; Wickham, Rita; Corbi, Dominick

2006-11-27

To review the literature regarding the incidence, current practice, guideline recommendations, nursing management, and knowledge gaps relevant to vesicant extravasation. Published research articles, books, case reports, and national guidelines. Vesicant extravasation is a relatively rare but significant complication of chemotherapy administration. Extravasation may have a range of consequences that can cause serious physical and quality-of-life effects. Knowledge of risk factors and preventive measures can reduce patient risk. Data-based and empirical management strategies such as immediate local measures (agent withdrawal, comfort measures, and medical interventions) may minimize risk for extravasation, as well as lead to timely recognition and management and decreased morbidity should extravasation occur. Vesicant extravasation and sequelae constitute a complex patient problem that clinicians should strive to prevent or to minimize injury should it occur. To this end, clinicians must demonstrate awareness of risks and use specialized knowledge while administering vesicant agents. Only nurses knowledgeable about extravasation and skilled in associated techniques should assume responsibility for vesicant administration.

[Extravasation of Cytostatic Drugs - Prevention and Best Practices].

PubMed

Maňásek, V

2016-01-01

Extravasation is the leakage of a drug (intended primarily for intravenous administration) into tissues surrounding the vascular system. The damage to surrounding varies depending on the nature and volume of extravasation. Cytostatic extravasation is associated with poor outcomes for patients. This paper summarizes the types of risk associated with cytostatic extravasation, and the preventative measures that can be used when such an event occurs. We also provide information on potential treatments. However, justification for their use has only been substantiated in papers with different levels of significance and these papers are not available in all countries. We summarize current international recommendations for actions to be taken in the event of extravasation.

Incidence of intravenous contrast extravasation: increased risk for patients with deep brachial catheter placement from the emergency department.

PubMed

Hardie, Andrew D; Kereshi, Borko

2014-06-01

Deep brachial intravenous catheter (IV) placement can be performed in emergency department patients with difficult vascular access, but the safety of deep brachial IV for iodinated contrast administration has not been assessed. This study compares the relative risk for extravasation of deep brachial IV compared with antecubital IV during power injected computed tomography (CT) examinations. A departmental practice quality improvement was performed to assess the rate of IV extravasation for all CT examinations during a 1 year period. De-identified data was analyzed with a waiver of informed consent to identify the rate and relative risk of iodinated contrast extravasation by catheter type. A total of 10,750 injections were performed, with 82 extravasation events (0.8 %). There were 51 extravasations of antecubital IV from approximately 8,599 placed (0.6 %). For 123 deep brachial IV placed, there were eight extravasations (6.5 %). The relative risk of a deep brachial IV extravasation was 9.4 compared to 0.4 for antecubital placement. Deep brachial IV demonstrated a markedly higher rate of contrast extravasation than antecubital IV. For power injected iodinated contrast administration, it is recommended to avoid the use of deep brachial IV whenever possible.

Extravasation injury in a paediatric population.

PubMed

Murphy, Adrian D; Gilmour, Robert F; Coombs, Chris J

2017-07-06

Extravasation occurs when a drug is inadvertently administered outside of the vein. Depending on the substance involved, this may lead to tissue necrosis with significant long-term morbidity. Children, particularly neonates, are particularly susceptible to extravasation with up to 70% of children in neonatal intensive care unit having some form of extravasation injury. These injuries are commonly referred to plastic surgeons for ongoing management. We prospectively collected information on all extravasation injuries referred to the plastic surgery department in a children's hospital over an 18-month period. Data collected included the agent involved in the extravasation, treatment and outcomes. In total, there were 43 extravasation injuries recorded on the hospital risk management system during the period of this study. All of these were referred to the plastic surgery team for ongoing management. Five patients (11%) underwent washout of their injuries. Three patients (7%) suffered injuries, which led to significant tissue necrosis, delayed healing and prolonged morbidity. Smaller infants, particularly those being cared for in an intensive care setting, are at increased risk for extravasation injury. Early referral and treatment of high-risk extravasation injuries may reduce the incidence of tissue loss and morbidity. © 2017 Royal Australasian College of Surgeons.

Level of adherence to an extravasation protocol over 10 years in a tertiary care hospital.

PubMed

Molas-Ferrer, Gloria; Farré-Ayuso, Elisabet; doPazo-Oubiña, Fernando; deAndrés-Lázaro, Ana; Guell-Picazo, Jaume; Borrás-Maixenchs, Núria; Corominas-Bosch, Lourdes; Valverde-Bosch, Montserrat; Creus-Baró, Natalia

2015-04-01

Extravasation of chemotherapy is an undesirable complication related to the administration of antineoplastic therapy. Establishing the real incidence is difficult. Because of the importance of a quick intervention after an extravasation, every hospital should have an extravasation protocol. The purpose of this study was to determine the degree of observance of an extravasation protocol by nursing staff and to determine extravasation incidence. This descriptive, longitudinal, retrospective study was set in a tertiary-level hospital. The researchers reviewed 117 extravasation notification forms received by the pharmacy department during a 10-year period. Nursing actuation, particularly observance of the extravasation protocol, was analyzed. Protocol adherence was 89%. Twelve deviations from the protocol in the application of recommended measures were detected. An antidote was used in 41 patients, and temperature measures were applied in 14 cases. Ninety-nine patients had at least one episode of reported follow-up. No cases of necrosis or skin ulcers were described, except by one patient, who developed a delayed skin ulcer to vinorelbine. Drugs most frequently reported were etoposide, carboplatin, and paclitaxel. Nursing staff should be continuously trained in extravasation protocol because a rapid actuation can prevent skin lesions.

Extravasation of chemotherapy.

PubMed

Langer, Seppo W

2010-07-01

Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led to the development of international guidelines that have proven useful tools in daily clinical practice. Moreover, the tissue destruction in one of the most dreaded types of extravasation (ie, anthracycline extravasation) now can effectively be prevented with a specific antidote, dexrazoxane.

MRI and CT contrast media extravasation: A systematic review.

PubMed

Heshmatzadeh Behzadi, Ashkan; Farooq, Zerwa; Newhouse, Jeffery H; Prince, Martin R

2018-03-01

This systematic review combines data from multiple papers on contrast media extravasation to identify factors contributing to increased extravasation risk. Data were extracted from 17 papers reporting 2191 extravasations in 1,104,872 patients (0.2%) undergoing computed tomography (CT) or magnetic resonance imaging (MRI). Extravasation rates were 0.045% for gadolinium-based contrast agents (GBCA) and nearly 6-fold higher, 0.26% for iodinated contrast agents. Factors associated with increased contrast media extravasations included: older age, female gender, using an existing intravenous (IV) instead of placing a new IV in radiology, in-patient status, use of automated power injection, high injection rates, catheter location, and failing to warm up the more viscous contrast media to body temperature. Contrast media extravasation is infrequent but nearly 6 times less frequent with GBCA for MRI compared with iodinated contrast used in CT.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies.

PubMed

Silva-Rodríguez, Jesús; Aguiar, Pablo; Sánchez, Manuel; Mosquera, Javier; Luna-Vega, Víctor; Cortés, Julia; Garrido, Miguel; Pombar, Miguel; Ruibal, Alvaro

2014-05-01

Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manual ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva-Rodríguez, Jesús, E-mail: jesus.silva.rodriguez@sergas.es; Aguiar, Pablo, E-mail: pablo.aguiar.fernandez@sergas.es; Servicio de Medicina Nuclear, Complexo Hospitalario Universidade de Santiago de Compostela

Purpose: Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. Methods: One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manualmore » ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Results: Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. Conclusions: The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.« less

Extravasation injuries.

PubMed

Hannon, Michael G; Lee, Steve K

2011-12-01

Extravasation injuries occur under a wide variety of circumstances in the inpatient setting. Prevention remains the ideal treatment for these iatrogenic injuries. When extravasation injuries do occur, they must be diagnosed and treated promptly to minimize the amount of soft tissue injury. Initial management is similar among vesicant extravasates. Although evidence is limited to guide management for specific extravasates, it is paramount to be aware of the described treatments and principles. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Nursing role model for computed tomography contrast injection decreases extravasation rates.

PubMed

Kadom, Nadja; Hashim, Hayder D; Olsen, Cara; Cefaratti, Marjean; Bulas, Dorothy; Shalaby-Rana, Eglal

2012-04-01

Extravasation of intravenous contrast administered for computed tomography remains of concern in pediatric patients. It is of great interest to any pediatric radiology department to decrease extravasation events in an effort to reduce even small adverse outcomes and improve the overall patient experience in the radiology department. Here, a total of 17 extravasation events, as reported and documented in departmental quality assurance at our institution over 4 years, were retrospectively reviewed for factors contributing to the number of adverse extravasation events. We found that pediatric nursing plays a central role in both achieving and maintaining a low extravasation rate at our institution. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of heparin fractions on the prevention of skin necrosis resulting from adriamycin extravasation: an experimental study.

PubMed

Askar, Ibrahim; Erbas, M Kemal; Gurlek, Ali

2002-09-01

Extravasation of a chemotherapeutic agent is one of the most frequent complications in cancer patients. Full-thickness skin necrosis often occurs after extravasation. Alternative approaches to treatment are local wound care, elevation, and hypothermia. It was shown that heparin prevents skin necrosis. In this experimental study, the effects of heparin fractions on the prevention of skin necrosis were compared by applying an extravasation model of Adriamycin in rats. Forty Sprague-Dawley male rats weighing 250 to 300 g were used. A total of 0.3 ml doxorubicin hydrochloride was administered subcutaneously to all rats. Ten minutes later, in the control group (group I), 1 ml normal saline was administered subcutaneously. In the first experimental group (group II), 100 U per day heparin sodium was administered in a volume of 1 ml subcutaneously. In the second experimental group (group III), nadroparin calcium (5 anti-Xa U per kilogram per day) was administered. In the third and last experimental group (group IV), dalteparin sodium (5 anti-Xa U per kilogram per day) was administered. All drugs were administered for 2 weeks. Necrotic areas were measured 4 weeks later. Statistical analysis was performed using the Kruskal-Wallis analysis of variance and the Mann-Whitney test. Heparin fractions caused a decreased ulcer rate and size than controls ( < 0.05). There was no superiority among heparin fractions. The authors think that low-molecular weight heparins are preferred, considering the higher risk of bleeding with unfractionated heparin.

Treatment of Cutaneous Injuries of Neonates Induced by Drug Extravasation with Hyaluronidase and Hirudoid

PubMed Central

Yan, Ya-Min; Fan, Qiao-Ling; Li, Ai-Qiu; Chen, Jia-Ling; Dong, Fei-Fei; Gong, Mei

2014-01-01

Objective: To analyze the effects of hyaluronidase and hirudoid treatment on drug extravasation in neonates. Methods: The medical records of 13 neonates with drug extravasation treated with hyaluronidase and hirudoid between August 1st, 2010 and May 1st, 2012 were analyzed retrospectively. The treatment procedure for drug extravasation adhered to the protocol in neonatal department. The information including age, sex, weight, diagnosis, size of affected area, site of extravasation and treatment was collected. Findings : The extravasation injuries alleviated and the symptoms improved after treatment, no adverse drug effects were reported with use of hyaluronidase and hirudoid. Conclusion: The treatment appeared to be beneficial in the management of extravasations of various medications in neonates and may be useful in reducing the severity of cutaneous toxicosis. However, further studies with large samples are still needed to assess the effectiveness and safety of hyaluronidase and hirudoid. PMID:25755854

Treatment of cutaneous injuries of neonates induced by drug extravasation with hyaluronidase and hirudoid.

PubMed

Yan, Ya-Min; Fan, Qiao-Ling; Li, Ai-Qiu; Chen, Jia-Ling; Dong, Fei-Fei; Gong, Mei

2014-08-01

To analyze the effects of hyaluronidase and hirudoid treatment on drug extravasation in neonates. The medical records of 13 neonates with drug extravasation treated with hyaluronidase and hirudoid between August 1(st), 2010 and May 1(st), 2012 were analyzed retrospectively. The treatment procedure for drug extravasation adhered to the protocol in neonatal department. The information including age, sex, weight, diagnosis, size of affected area, site of extravasation and treatment was collected. Findings : The extravasation injuries alleviated and the symptoms improved after treatment, no adverse drug effects were reported with use of hyaluronidase and hirudoid. The treatment appeared to be beneficial in the management of extravasations of various medications in neonates and may be useful in reducing the severity of cutaneous toxicosis. However, further studies with large samples are still needed to assess the effectiveness and safety of hyaluronidase and hirudoid.

Treatment of experimental extravasation of amrubicin, liposomal doxorubicin, and mitoxantrone with dexrazoxane.

PubMed

Langer, Seppo W; Thougaard, Annemette V; Sehested, Maxwell; Jensen, Peter Buhl

2012-02-01

Dexrazoxane is an established treatment option in extravasation of the classic anthracyclines such as doxorubicin, epirubicin, and daunorubicin. However, it is not known whether the protection against the devastating tissue injuries extends into extravasation with new types of anthracyclines, the anthracenediones, or the liposomal pegylated anthracycline formulations. We therefore tested the antidotal efficacy of dexrazoxane against extravasation of amrubicin, mitoxantrone, and liposomal pegylated doxorubicin in mice. A total of 80 female B6D2F1 mice were tested in an established mouse extravasation model. The mice had experimental extravasations of amrubicin, mitoxtanrone, and Caelyx and were immediately hereafter treated with systemic dexrazoxane or saline. Systemic treatment with dexrazoxane resulted in significant protection against extravasation injuries from all three drugs. Moreover, the vesicant potential of the three test drugs was weaker than seen in previous experiments with the classic anthracyclines.

MRI and CT contrast media extravasation

PubMed Central

Heshmatzadeh Behzadi, Ashkan; Farooq, Zerwa; Newhouse, Jeffery H.; Prince, Martin R.

2018-01-01

Abstract Background: This systematic review combines data from multiple papers on contrast media extravasation to identify factors contributing to increased extravasation risk. Methods: Data were extracted from 17 papers reporting 2191 extravasations in 1,104,872 patients (0.2%) undergoing computed tomography (CT) or magnetic resonance imaging (MRI). Results: Extravasation rates were 0.045% for gadolinium-based contrast agents (GBCA) and nearly 6-fold higher, 0.26% for iodinated contrast agents. Factors associated with increased contrast media extravasations included: older age, female gender, using an existing intravenous (IV) instead of placing a new IV in radiology, in-patient status, use of automated power injection, high injection rates, catheter location, and failing to warm up the more viscous contrast media to body temperature. Conclusion: Contrast media extravasation is infrequent but nearly 6 times less frequent with GBCA for MRI compared with iodinated contrast used in CT. PMID:29489663

Spatiotemporal expression dynamics of selectins govern the sequential extravasation of neutrophils and monocytes in the acute inflammatory response.

PubMed

Zuchtriegel, Gabriele; Uhl, Bernd; Hessenauer, Maximilian E T; Kurz, Angela R M; Rehberg, Markus; Lauber, Kirsten; Krombach, Fritz; Reichel, Christoph A

2015-04-01

Leukocyte recruitment to the site of inflammation is a key event in a variety of cardiovascular pathologies. Infiltrating neutrophils constitute the first line of defense that precedes a second wave of emigrating monocytes reinforcing the inflammatory reaction. The mechanisms initiating this sequential process remained largely obscure. Using advanced in vivo microscopy and in vitro/ex vivo techniques, we identified individual spatiotemporal expression patterns of selectins and their principal interaction partners on neutrophils, resident/inflammatory monocytes, and endothelial cells. Coordinating the intraluminal trafficking of neutrophils and inflammatory monocytes to common sites of extravasation, selectins assign different sites to these immune cells for their initial interactions with the microvascular endothelium. Whereas constitutively expressed leukocyte L-selectin/CD62L and endothelial P-selectin/CD62P together with CD44 and P-selectin glycoprotein ligand-1/CD162 initiate the emigration of neutrophils, de novo synthesis of endothelial E-selectin/CD62E launches the delayed secondary recruitment of inflammatory monocytes. In this context, P-selectin/CD62P and L-selectin/CD62L together with P-selectin glycoprotein ligand-1/CD162 and CD44 were found to regulate the flux of rolling neutrophils and inflammatory monocytes, whereas E-selectin/CD62E selectively adjusts the rolling velocity of inflammatory monocytes. Moreover, selectins and their interaction partners P-selectin glycoprotein ligand-1/CD162 and CD44 differentially control the intraluminal crawling behavior of neutrophils and inflammatory monocytes collectively enabling the sequential extravasation of these immune cells to inflamed tissue. Our findings provide novel insights into the mechanisms initiating the sequential infiltration of the perivascular tissue by neutrophils and monocytes in the acute inflammatory response and might thereby contribute to the development of targeted therapeutic strategies for prevention and treatment of cardiovascular diseases. © 2015 American Heart Association, Inc.

The role of substance P release in the lung with esophageal acid.

PubMed

Kohrogi, H; Hamamoto, J; Kawano, O; Iwagoe, H; Fujii, K; Hirata, N; Ando, M

2001-12-03

To investigate whether tachykinins are released in the airways by stimulating the esophagus, airway plasma extravasation induced by intraesophageal hydrochloric acid (HCl) in the presence or absence of the neutral endopeptidase (NEP) inhibitor phosphoramidon and the neurokinin-1-receptor antagonist FK888 was studied in anesthetized guinea pigs. Airway plasma extravasation also was studied in the presence of the NEP inhibitor in guinea pigs pretreated with capsaicin or bilateral vagotomy. Propranolol and atropine were used in all animals to block adrenergic and cholinergic nerve effects. Airway plasma leakage was evaluated by measuring extravasated Evans blue dye. One normal HCl infusion into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation induced by HCl infusion into the esophagus in the trachea and main bronchi, and FK888 significantly inhibited extravasation in a dose-related manner. In capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilaterally vagotomized animals. These results suggest that locally acting substances are released by intraesophageal HCl stimulation that cause airway plasma extravasation. These substances are generated through activation of neural pathways, including some that traffic through the vagus nerves that link the esophagus or airways.

CT contrast extravasation in the upper extremity: strategies for management.

PubMed

Sbitany, Hani; Koltz, Peter F; Mays, Chester; Girotto, John A; Langstein, Howard N

2010-01-01

Extravasation of CT scan contrast media into upper extremity subcutaneous tissue is a relatively frequent complication of injection. Potential sequelae of extravasation include compartment syndrome, skin sloughing, and necrosis. Many institutions institute protocols requiring inpatient plastic surgery consultations immediately following extravasation injury to the upper extremity. We hypothesize that conversion to non-ionic contrast media for contrast CT studies has greatly reduced the incidence of severe extravasation injuries, and may alleviate the need for routine hand surgery consultations. Records from 102 consecutive CT contrast media extravasation injuries were identified. Data acquired from a single institution included type and amount of contrast extravasated, anatomic location, post-procedural clinical symptoms, whether consult was obtained, and final recommendations and outcome. In 102 consecutive cases, immediate surgical therapy was necessary in 0. Non-ionic medium was used in 94% of these cases, and ionic dye was used in 6%. Extravasation of less than 100 cc occurred in 90%, and only 10% were greater. Plastic surgery consultation was immediately obtained in 42% of cases. Factors prompting consultation included extravasation >30 cc, and the presence of erythema or induration. Trends for consultation remained without discernable pattern when patients were stratified by age, amount of extravasate, or anatomic location. Conservative management was recommended in all cases. This included elevation of the extremity, frequent pulse and sensation exams, local message, and temporary splinting. There were no secondary complications requiring surgical intervention. Extravasation of non-ionic CT contrast media appears to be innocuous and can be treated with conservative therapy. Plastic surgery consultation should be obtained when there are obvious signs of skin and soft tissue compromise or symptoms of compartment syndrome. Copyright 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Retinal plasma extravasation in streptozotocin-diabetic rats mediated by kinin B1 and B2 receptors

PubMed Central

Abdouh, M; Talbot, S; Couture, R; Hasséssian, H M

2008-01-01

Background and purpose: We investigated whether or not kinin receptors play a role in diabetic blood–retinal barrier breakdown, which is a leading cause of vision loss. Experimental approach: Blood–retinal barrier breakdown was quantified using Evans blue, and expression of kinin B1 receptor mRNA was measured using quantitative reverse transcrition-PCR. Diabetic rats (streptozotocin (STZ), 65 mg kg−1) received a single intraocular injection of bradykinin (BK) or des-Arg9-BK, alone, or in combination with antagonists for B1 (des-Arg10-Hoe140, R-715) and/or B2 (Hoe140) receptors, given intraocularly or intravenously (i.v.). Key results: In control rats, BK (0.1–10 nmol) dose-dependently increased plasma extravasation, which was inhibited by Hoe140 (0.2 nmol), whereas des-Arg9-BK (0.1 and 1 nmol) was without effect. B1 receptor mRNA was markedly increased in retinas of diabetic rats, and this was prevented by N-acetyl-L-cysteine (1 g kg−1 day−1 for 7 days). Plasma extravasation in retinas of STZ-diabetic rats was higher than in controls and enhanced by des-Arg9-BK. Response to des-Arg9-BK was inhibited by intraocular or i.v. injection of B1 receptor antagonists. Diabetes-induced plasma extravasation was inhibited only by a combination of des-Arg10-Hoe140 and Hoe 140 (100 nmol kg−1, i.v. 15 min earlier) or by R-715 (1 μmol kg−1, i.v.) injected daily for 7 days. Conclusions and implications: Kinin B1 receptors are upregulated in retinas of STZ-diabetic rats through a mechanism involving oxidative stress. Both kinin B1 and B2 receptors contribute to increased plasma extravasation in diabetic retinopathy. Chronic inhibition of both kinin receptors, possibly with antioxidant adjuvants, may be a novel therapeutic strategy for diabetic retinopathy. PMID:18311190

Involvement of NMDA receptor mechanisms in jaw electromyographic activity and plasma extravasation induced by inflammatory irritant application to temporomandibular joint region of rats.

PubMed

Yu, X M; Sessle, B J; Haas, D A; Izzo, A; Vernon, H; Hu, J W

1996-11-01

The aim of this study was to examine the possible role of N-methyl-D-aspartate (NMDA) receptor mechanisms in responses induced by the small-fibre excitant and inflammatory irritant mustard oil injected into the temporomandibular joint (TMJ) region of rats. The effects of the non-competitive NMDA antagonist MK-801 were tested on the mustard oil-evoked increases in electromyographic (EMG) activity of the masseter and digastric muscles and Evans Blue plasma extravasation. Five minutes before the mustard oil injection, MK-801 or its vehicle was administered systemically (i.v.), into the third ventricle (i.c.v.), or locally into the TMJ region. Compared with control animals receiving vehicle, the rats receiving MK-801 at an i.v. dose of 0.5 mg/kg (n = 5) showed a significant reduction in the incidence and magnitude of EMG responses as well as in the plasma extravasation evoked by mustard oil; MK-801 at an i.v. dose of 0.1 mg/kg (n = 5) had no significant effect on plasma extravasation or on the incidence and magnitude of EMG responses but did significantly increase the latency of EMG responses. An i.c.v. dose of 0.1 mg/kg (n = 5) or 0.01 mg/kg (n = 5) had no significant effect on plasma extravasation or incidence of EMG responses but did significantly reduce the magnitudes of the masseter EMG response; the 0.01 mg/kg dose also significantly increased the latency of the digastric EMG response. The magnitudes of both the masseter and digastric EMG responses were also significantly reduced by MK-801 administered into the TMJ region at a dose of 0.1 mg/kg (n = 5) but not by 0.01 mg/kg (n = 5); neither dose significantly affected the incidence of EMG responses or the plasma extravasation. These data suggest that both central and peripheral NMDA receptor mechanisms may play an important role in EMG responses evoked by the small-fibre excitant and inflammatory irritant mustard oil, but that different neurochemical mechanisms may be involved in the plasma extravasation induced by mustard oil.

Extravasation of antineoplastic agents: prevention and treatments.

PubMed

Boschi, Rita; Rostagno, Elena

2012-07-31

The extravasation of antineoplastic agents is an unwanted and distressing situation that can easily occur. It may cause severe and irreversible local injuries. Left untreated, vesicant chemotherapy extravasation can potentially cause tissue necrosis, functional impairment and permanent disfigurement. This article provides a review of current literature regarding recommendations on the prevention and treatment of extravasation of antineoplastic agents.

Evaluation of the Predictive Validity of Thermography in Identifying Extravasation With Intravenous Chemotherapy Infusions.

PubMed

Matsui, Yuko; Murayama, Ryoko; Tanabe, Hidenori; Oe, Makoto; Motoo, Yoshiharu; Wagatsuma, Takanori; Michibuchi, Michiko; Kinoshita, Sachiko; Sakai, Keiko; Konya, Chizuko; Sugama, Junko; Sanada, Hiromi

Early detection of extravasation is important, but conventional methods of detection lack objectivity and reliability. This study evaluated the predictive validity of thermography for identifying extravasation during intravenous antineoplastic therapy. Of 257 patients who received chemotherapy through peripheral veins, extravasation was identified in 26. Thermography was performed every 15 to 30 minutes during the infusions. Sensitivity, specificity, positive predictive value, and negative predictive value using thermography were 84.6%, 94.8%, 64.7%, and 98.2%, respectively. This study showed that thermography offers an accurate prediction of extravasation.

Focal cutaneous squamous cell carcinoma following radium-223 extravasation.

PubMed

Benjegerdes, Katie E; Brown, Shannon C; Housewright, Chad D

2017-01-01

Long-term sequelae due to extravasation of intravenous radioisotopes resulting in radiation injuries are rarely reported. As the use of radioactive isotopes for the treatment of osteoblastic metastases increases, information regarding the prevention, treatment, and long-term monitoring of suspected extravasation injury will become increasingly important. We present a patient with no previous history of skin cancer who developed an aggressive cutaneous squamous cell carcinoma at the site of prior radium-223 extravasation. We recommend that patients who experience extravasation of therapeutic radioisotopes be monitored by dermatologists for long-term sequelae. Cutaneous squamous cell carcinoma should be recognized as a rare but potential adverse event following cutaneous extravasation of radium-223 and is likely a side effect that is severely underreported.

Allergen challenge-induced extravasation of plasma in mouse airways.

PubMed

Erjefält, J S; Andersson, P; Gustafsson, B; Korsgren, M; Sonmark, B; Persson, C G

1998-08-01

Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice. This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin. Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma. Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent. The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation

[Extravasation of cytostatic agents: a serious complication of oncological treatment].

PubMed

Alfaro-Rubio, Alberto; Sanmartín, Onofre; Requena, Celia; Llombart, Beatriz; Botella-Estrada, Rafael; Nagore, Eduardo; Serra-Guillén, Carlos; Hueso, Luis; Guillén, Carlos

2006-04-01

The extravasation of cytostatic agents is a known, serious situation that can easily occur and cause chronic, irreversible damage. The incidence of extravasation ranges from 0.1 %-6.5 %, according to different studies. Many cases of extravasation can be prevented by systematizing the administration techniques for cytostatic agents. We present the clinical and histological characteristics of a series of patients with extravasation lesions. Included in the study were all patients treated with chemotherapy who developed localized lesions in the area of the cytostatic injection after extravasation was detected during administration. The patients were studied and followed up for a three-year period, from January 2000 to December 2003, inclusive. We found nine cases of extravasation among the 2,186 patients who were treated with chemotherapy, which represents an incidence of 0.41 %, and 3.4 % of all chemotherapy-induced skin lesions. The cytostatic agent most often involved was vinorelbine, and the most frequent location was the antecubital fossa. The intensity of the lesions made it necessary to delay the next cycle of treatment in 55 % of the cases. The histological findings varied depending on when the biopsy was done, showing panniculitis with low cellularity together with epidermal lesions attributable to direct cytotoxicity. The best treatment for extravasation is prevention, but when it has already occurred, measures vary depending on the cytostatic drug extravasated and the intensity of the lesions. Conservative measures are advisable before surgery.

Reducing the morbidity from extravasation injuries.

PubMed

Khan, Mansoor S; Holmes, J D

2002-06-01

Extravasation is defined as the leakage of solutions from the vein. This may cause damage to surrounding tissue during intravenous fluid administration. Extravasation has an incidence of 5% of all cytotoxic drug administrations. In the authors' hospital, a protocol has been set up using the dilution flush-out technique. Extravasation packs containing cannulae, normal saline, hyaluronidase, and instructions on how to manage extravasation injuries, accompanied by an audit sheet to assist follow-up, have been introduced to allow the treatment of extravasation at the ward level in an attempt to reduce morbidity from the injury. Between December 1997 and December 1999, 18 adult patients were identified with extravasation injuries after the administration of cytotoxic medication. Seventeen were treated immediately according to the protocol. One, however, was not. Patients were followed-up for 6 months after injury. The 17 patients treated immediately needed no further surgical intervention, whereas the 1 patient not treated needed a split skin graft to cover the defect. The authors recommend the placement of "extravasation packs" on all wards where cytotoxic drugs are prescribed and that all staff members are familiar with this regime. These steps help to reduce the morbidity of a potentially damaging injury.

Rat injury model of docetaxel extravasation.

PubMed

Zhu, Jing-Jing; Fu, Jian-Fei; Yang, Jiao; Hu, Bing; Zhang, Hui; Yu, Jian-Hua

2014-09-01

Docetaxel is a novel type of chemotherapy drug that actively treats a number of malignant tumors. The aim of the present study was to explore the severity and natural course of tissue damage induced by docetaxel extravasation and to confirm the vesicant potential of docetaxel. Rats were selected for the establishment of the ulcer model. Different volumes and concentrations were explored to induce the skin ulcer and to confirm the optimum rational injection model. The natural course of tissue injury and pathological changes produced by docetaxel extravasation were observed by comparing to vinorelbine extravasation. A 0.4 ml volume and a 6 mg/ml concentration were the optimum rational injection model for the induction of the skin ulcer. The docetaxel extravasation induced local tissue necrosis, followed by granuloma formation and hyperpigmentation or scar formation. The severity of the injury depended on the concentration of the extravasation used in the rat model. The injury occurred on the first day following extravasation and lasted 4-6 weeks. The damage from docetaxel was weaker than vinorelbine in association with the depth and extension of necrosis. In conclusion, docetaxel extravasation can induce tissue necrosis. However, the severity of necrosis was weaker than that of vinorelbine. Docetaxel has superficial vesicant properties.

Rat injury model of docetaxel extravasation

PubMed Central

ZHU, JING-JING; FU, JIAN-FEI; YANG, JIAO; HU, BING; ZHANG, HUI; YU, JIAN-HUA

2014-01-01

Docetaxel is a novel type of chemotherapy drug that actively treats a number of malignant tumors. The aim of the present study was to explore the severity and natural course of tissue damage induced by docetaxel extravasation and to confirm the vesicant potential of docetaxel. Rats were selected for the establishment of the ulcer model. Different volumes and concentrations were explored to induce the skin ulcer and to confirm the optimum rational injection model. The natural course of tissue injury and pathological changes produced by docetaxel extravasation were observed by comparing to vinorelbine extravasation. A 0.4 ml volume and a 6 mg/ml concentration were the optimum rational injection model for the induction of the skin ulcer. The docetaxel extravasation induced local tissue necrosis, followed by granuloma formation and hyperpigmentation or scar formation. The severity of the injury depended on the concentration of the extravasation used in the rat model. The injury occurred on the first day following extravasation and lasted 4–6 weeks. The damage from docetaxel was weaker than vinorelbine in association with the depth and extension of necrosis. In conclusion, docetaxel extravasation can induce tissue necrosis. However, the severity of necrosis was weaker than that of vinorelbine. Docetaxel has superficial vesicant properties. PMID:25054005

Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish

PubMed Central

Kanada, Masamitsu; Zhang, Jinyan; Yan, Libo; Sakurai, Takashi

2014-01-01

The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies. PMID:25551022

Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish.

PubMed

Kanada, Masamitsu; Zhang, Jinyan; Yan, Libo; Sakurai, Takashi; Terakawa, Susumu

2014-01-01

The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies.

Overview, prevention and management of chemotherapy extravasation.

PubMed

Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

2016-02-10

Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused.

Overview, prevention and management of chemotherapy extravasation

PubMed Central

Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

2016-01-01

Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused. PMID:26862492

Evaluation of the Predictive Validity of Thermography in Identifying Extravasation With Intravenous Chemotherapy Infusions

PubMed Central

Murayama, Ryoko; Tanabe, Hidenori; Oe, Makoto; Motoo, Yoshiharu; Wagatsuma, Takanori; Michibuchi, Michiko; Kinoshita, Sachiko; Sakai, Keiko; Konya, Chizuko; Sugama, Junko; Sanada, Hiromi

2017-01-01

Early detection of extravasation is important, but conventional methods of detection lack objectivity and reliability. This study evaluated the predictive validity of thermography for identifying extravasation during intravenous antineoplastic therapy. Of 257 patients who received chemotherapy through peripheral veins, extravasation was identified in 26. Thermography was performed every 15 to 30 minutes during the infusions. Sensitivity, specificity, positive predictive value, and negative predictive value using thermography were 84.6%, 94.8%, 64.7%, and 98.2%, respectively. This study showed that thermography offers an accurate prediction of extravasation. PMID:29112585

Contrast Media Extravasation in CT and MRI - A Literature Review and Strategies for Therapy.

PubMed

Mandlik, Veronika; Prantl, Lukas; Schreyer, Andreas G

2018-06-18

 Contrast extravasation events in daily radiological routine may lead to serious complications, especially during CT examinations. The resulting symptoms may vary from local pain up to skin ulcers, necrosis or even acute compartment syndrome.There are no uniformly accepted radiological guidelines or recommendations regarding detection and treatment of extravasation events and immanent complications in a timely manner.  Systematic literature research considering the last 35 years via PubMed using search terms "contrast medium extravasation/paravasation".  In the literature, there are conservative management approaches of contrast media extravasation without major evidence base, such as unguent dressings, cooling or splinting. This therapy is mostly symptomatic. Additionally, various invasive techniques are described. We discuss these techniques in the context of contemporary literature, such as the hyaluronidase Injection into the site of extravasation, suction/aspiration technique including flushing of the affected tissue areas and the squeezing technique. However, most citations lack scientific evidence: many articles include anecdotal enumerations, case studies or cite publications from the era, when ionic high osmolar contrast media was state-of-the-art. Besides, many authors derive their extravasation management from studies, where agents other than contrast media were investigated.  After detailed literature review, we suggest early (plastic) surgical consultation when non-ionic, low-osmolar contrast medium extravasation is about 150 cc or more. In case of extravasation less than 150 cc but in presence of additional symptoms such as impaired perfusion or altered sensibility, the (plastic) surgeon should also be consulted instantly. We do not recommend any invasive first line therapy when contrast media extravasation is less than 150 cc and the patient presents no additional symptoms, besides swelling and local pain. Nevertheless continuous monitoring and accurate conservative management such as active cooling and elevation, splinting of the affected extremity are mandatory as early detection of critical symptoms helps to initiate prompt surgical intervention and avoid sequelae.   · Morbidity after contrast media extravasation is extremely rare.. · Predicting sequelae after contrast extravasation is difficult at first sight.. · Treatments such as hyaluronidase injection, suction/aspiration, squeeze technique have been described.. · Surgical consultation is recommended for extravasation > 150 cc or when additional symptoms occur.. · Mandlik V, Prantl L, Schreyer AG. Contrast Media Extravasation in CT and MRI - A Literature Review and Strategies for Therapy. Fortschr Röntgenstr 2018; DOI: 10.1055/a-0628-7095. © Georg Thieme Verlag KG Stuttgart · New York.

Frequency, outcome, and risk factors of contrast media extravasation in 142,651 intravenous contrast-enhanced CT scans.

PubMed

Hwang, Eui Jin; Shin, Cheong-Il; Choi, Young Hun; Park, Chang Min

2018-06-06

To evaluate the frequency, outcome, and risk factors of intravenous contrast media (CM) extravasation during contrast-enhanced CT scans in a large population. After institutional review board approval, 142,651 patients (72,976 males and 69,675 females; mean age, 59.9 ± 13.0 years) who underwent contrast-enhanced CT scans with intravenous CM between January 2015 and April 2017 were retrospectively included. The frequency of CM extravasations and their clinical outcomes were investigated. Risk factors of CM extravasation were evaluated using logistic regression with generalized estimating equation analyses. In addition, the frequency and risk factors of large-volume (≥100 ml) CM extravasation were also investigated. CM extravasation occurred in 0.23% (321/142,651) of patients, all of which were of mild degree and resolved without any sequelae through conservative management. Multivariate analysis revealed that female gender [odds ratio (OR) = 1.61; p < 0.001], 60 < age ≤ 70 years (OR = 1.71; p = 0.004) or age > 70 years (OR = 2.49; p < 0.001), patients in general wards (OR = 2.71; p < 0.001) or ICUs (OR = 4.76; p < 0.001), 9.4 < CM viscosity ≤ 10.0 (OR = 1.65; p = 0.015), 10.0 < CM viscosity ≤ 10.6 (OR = 1.60; p = 0.002), and CM viscosity > 16.0 (OR = 2.55, p < 0.001) were independent risk factors for CM extravasation. CM extravasation during contrast-enhanced CT scans was uncommon with no substantial clinical consequences. Several risk factors that may have the potential to reduce the occurrence of CM extravasation were identified. • The observed frequency of contrast media extravasation during contrast-enhanced CT scans was 0.23% (321/142,651). • Significant risk factors for contrast media extravasation were female gender, age older than 60 years, patients in general wards or ICUs, and the viscosity of contrast media greater than 9.4 mPa∙s. • The main preventive action for contrast media extravasation would be to lower the viscosity of contrast media.

Successful experience utilizing dexrazoxane treatment for an anthracycline extravasation.

PubMed

Tyson, Abby Mercer; Gay, Wendy E

2010-05-01

To describe a successful case of dexrazoxane treatment after an extravasation of doxorubicin and share a creative solution for formulary cost management. A 42-year-old female diagnosed with breast cancer was receiving doxorubicin as adjuvant treatment. The patient recently underwent a right mastectomy for a 3-centimeter grade 3 invasive ductal carcinoma. Three of 20 lymph nodes were positive, and the patient was stage 2B at presentation, with an estrogen receptor/progesterone receptor-positive and HER-2/neu-negative tumor. At an outside hospital, the patient was receiving doxorubicin through an infusion port when extravasation was noted after approximately 15 mL had been infused. She was transferred to Riverside Methodist Hospital and dexrazoxane treatment was initiated within 6 hours after extravasation. She received a full 3-day course of dexrazoxane treatment without complication and was discharged home. Significant delays in chemotherapy administration were avoided, and the patient successfully completed her planned chemotherapy course. Dexrazoxane has the potential to minimize tissue damage and treatment delays after an anthracycline extravasation. Although dexrazoxane is commercially marketed for 2 separate treatment indications, Totect is the Food and Drug Administration-approved product for anthracycline extravasations. Facilities administering anthracyclines should proactively resolve how to obtain, process, prepare, and administer this antidote to a patient within 6 hours of an extravasation event. Developing a preprinted chemotherapy extravasation order may facilitate the incorporation of the most recent Oncology Nursing Society guidelines to utilize dexrazoxane for an anthracycline extravasation. Cost sharing with other institutions may offer a creative solution to lessen the financial impact of stocking dexrazoxane therapy. Ensuring expedient treatment and accessibility to dexrazoxane therapy after an anthracycline extravasation is critical to the success of the treatment. All facilities utilizing anthracycline chemotherapy should purchase dexrazoxane or secure agreements with other facilities to guarantee the administration of this medication should extravasation occur.

Evaluation of a near-infrared-type contrast medium extravasation detection system using a swine model.

PubMed

Ishihara, Toshihiro; Kobayashi, Tatsushi; Ikeno, Naoya; Hayashi, Takayuki; Sakakibara, Masahiro; Niki, Noboru; Satake, Mitsuo; Moriyama, Noriyuki

2014-01-01

To refine the development and evaluate the near-infrared (NIR) extravasation detection system and its ability to detect extravasation during a contrast-enhanced computed tomography (CT) examination. The NIR extravasation detection system projects the NIR light through the surface of the human skin then, using its sensory system, will monitor the changes in the amount of NIR that reflected, which varies based on absorption properties.Seven female pigs were used to evaluate the contrast media extravasation detection system, using a 20-gauge intravenous catheter, when injected at a rate of 1 mL/s into 4 different locations just under the skin in the thigh section. Using 3-dimensional CT images, we evaluated the extravasations between time and volume, depth and volume, and finally depth and time to detect. We confirmed that the NIR light, 950-nm wavelength, used by the extravasation detection system is well absorbed by contrast media, making changes easy to detect. The average time to detect an extravasation was 2.05 seconds at a depth of 2.0 mm below the skin with a volume of 1.3 mL, 2.57 seconds at a depth between 2.1 and 5 mm below the skin and a volume of 3.47 mL, 10.5 seconds for depths greater than 5.1 mm and a volume of 11.1 mL. The detection accuracy was significantly deteriorated when the depth exceeded 5.0 mm (Tukey-Kramer, P < 0.05) CONCLUSIONS: The extravasation system detection system that is using NIR has a high level of detection sensitivity. The sensitivity enables the system to detect extravasation at depths less than 2 mm with a volume of 1.5 mL and at depths less than 5 mm with a volume of 3.5 mL. The extravasation detection system could be suitable for use during examinations.

Central Action of Peripherally Applied Botulinum Toxin Type A on Pain and Dural Protein Extravasation in Rat Model of Trigeminal Neuropathy

PubMed Central

Filipović, Boris; Matak, Ivica; Bach-Rojecky, Lidija; Lacković, Zdravko

2012-01-01

Background Infraorbital nerve constriction (IoNC) is an experimental model of trigeminal neuropathy. We investigated if IoNC is accompanied by dural extravasation and if botulinum toxin type A (BoNT/A) can reduce pain and dural extravasation in this model. Methodology/Principal Findings Rats which developed mechanical allodynia 14 days after the IoNC were injected with BoNT/A (3.5 U/kg) into vibrissal pad. Allodynia was tested by von Frey filaments and dural extravasation was measured as colorimetric absorbance of Evans blue - plasma protein complexes. Presence of dural extravasation was also examined in orofacial formalin-induced pain. Unilateral IoNC, as well as formalin injection, produced bilateral dural extravasation. Single unilateral BoNT/A injection bilaterally reduced IoNC induced dural extravasation, as well as allodynia (lasting more than 2 weeks). Similarly, BoNT/A reduced formalin-induced pain and dural extravasation. Effects of BoNT/A on pain and dural extravasation in IoNC model were dependent on axonal transport through sensory neurons, as evidenced by colchicine injections (5 mM, 2 µl) into the trigeminal ganglion completely preventing BoNT/A effects. Conclusions/Significance Two different types of pain, IoNC and formalin, are accompanied by dural extravasation. The lasting effect of a unilateral injection of BoNT/A in experimental animals suggests that BoNT/A might have a long-term beneficial effect in craniofacial pain associated with dural neurogenic inflammation. Bilateral effects of BoNT/A and dependence on retrograde axonal transport suggest a central site of its action. PMID:22238656

Extravasation Risk Using Ultrasound-guided Peripheral Intravenous Catheters for Computed Tomography Contrast Administration.

PubMed

Rupp, Jordan D; Ferre, Robinson M; Boyd, Jeremy S; Dearing, Elizabeth; McNaughton, Candace D; Liu, Dandan; Jarrell, Kelli L; McWade, Conor M; Self, Wesley H

2016-08-01

Ultrasound-guided intravenous catheter (USGIV) insertion is increasingly being used for administration of intravenous (IV) contrast for computed tomography (CT) scans. The goal of this investigation was to evaluate the risk of contrast extravasation among patients receiving contrast through USGIV catheters. A retrospective observational study of adult patients who underwent a contrast-enhanced CT scan at a tertiary care emergency department during a recent 64-month period was conducted. The unadjusted prevalence of contrast extravasation was compared between patients with an USGIV and those with a standard peripheral IV inserted without ultrasound. Then, a two-stage sampling design was used to select a subset of the population for a multivariable logistic regression model evaluating USGIVs as a risk factor for extravasation while adjusting for potential confounders. In total, 40,143 patients underwent a contrasted CT scan, including 364 (0.9%) who had contrast administered through an USGIV. Unadjusted prevalence of extravasation was 3.6% for contrast administration through USGIVs and 0.3% for standard IVs (relative risk = 13.9, 95% confidence interval [CI] = 7.9 to 24.6). After potential confounders were adjusted for, CT contrast administered through USGIVs was associated with extravasation (adjusted odds ratio = 8.6, 95% CI = 4.6 to 16.2). No patients required surgical management for contrast extravasation; one patient in the standard IV group was admitted for observation due to extravasation. Patients who received contrast for a CT scan through an USGIV had a higher risk of extravasation than those who received contrast through a standard peripheral IV. Clinicians should consider this extravasation risk when weighing the risks and benefits of a contrast-enhanced CT scan in a patient with USGIV vascular access. © 2016 by the Society for Academic Emergency Medicine.

Extravasation Risk Using Ultrasound Guided Peripheral Intravenous Catheters for Computed Tomography Contrast Administration

PubMed Central

Rupp, Jordan D.; Ferre, Robinson M.; Boyd, Jeremy S.; Dearing, Elizabeth; McNaughton, Candace D.; Liu, Dandan; Jarrell, Kelli L.; McWade, Conor M.; Self, Wesley H.

2016-01-01

Objective Ultrasound guided intravenous catheter (USGIV) insertion is increasingly being used for administration of intravenous contrast for computed tomography (CT) scans. The goal of this investigation was to evaluate the risk of contrast extravasation among patients receiving contrast through USGIV catheters. Methods A retrospective observational study of adult patients who underwent a contrast-enhanced CT scan at a tertiary-care emergency department during a recent 64-month period was conducted. The unadjusted prevalence of contrast extravasation was compared between patients with an USGIV and those with a standard peripheral IV inserted without ultrasound. Then, a two-stage sampling design was used to select a subset of the population for a multivariable logistic regression model evaluating USGIVs as a risk factor for extravasation while adjusting for potential confounders. Results In total, 40,143 patients underwent a contrasted CT scan, including 364 (0.9%) who had contrast administered through an USGIV. Unadjusted prevalence of extravasation was 3.6% for contrast administration through USGIVs and 0.3% for standard IVs (relative risk: 13.9, 95% CI: 7.7 to 24.6). After adjustment for potential confounders, CT contrast administered through USGIVs was associated with extravasation (adjusted odds ratio: 8.6; 95% CI: 4.6, 16.2). No patients required surgical management for contrast extravasation; one patient in the standard IV group was admitted for observation due to extravasation. Conclusions Patients who received contrast for a CT scan through an USGIV had a higher risk of extravasation than those who received contrast through a standard peripheral IV. Clinicians should consider this extravasation risk when weighing the risks and benefits of a contrast-enhanced CT scan in a patient with USGIV vascular access. PMID:27151898

An investigation into current protocols and radiographer opinions on contrast extravasation in Irish CT departments.

PubMed

Cleary, N; McNulty, J P; Foley, S J; Kelly, E

2017-11-01

Iodinated contrast extravasation is a serious complication associated with intravenous administration in radiology. Departmental protocols and the radiographer's approach on both prevention techniques and treatment will affect the prevalence of extravasation, and the eventual outcome for the patient when it does occur. To examine contrast extravasation protocols in place in Irish CT departments for alignment with European Society of Urogenital Radiology (ESUR) Guidelines (2014); to establish radiographer's opinions on contrast extravasation; and to examine radiographer adherence to protocols. Contrast extravasation protocols from a purposively selected sample of CT departments across Ireland (n = 6) were compared to ESUR guidelines, followed by an online survey of CT radiographers practicing in the participating centres. All participating CT departments (n = 5) had written protocols in place. High risk patients, such as elderly or unconscious, were identified in most protocols, however, children were mentioned in just one protocol and obese patients were not specified in any. The response rate of CT radiographers was 23% (n = 24). 58% (n = 14) of respondents indicated that contrast extravasation was more likely during CTA examinations. While high levels of confidence in managing extravasation were reported, suggested treatment approaches, and confidence in same, was more variable. Clinical workload in CT departments was also identified as a factor impacting on patient care and management. While contrast extravasation protocols were generally in line with ESUR Guidelines, high risk patients may not be getting sufficient attention. More radiographer awareness of patient monitoring needs, particularly in busy departments with a heavy workload may also reduce extravasation risk, and improve management of same. Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis.

PubMed

Tichet, Mélanie; Prod'Homme, Virginie; Fenouille, Nina; Ambrosetti, Damien; Mallavialle, Aude; Cerezo, Michael; Ohanna, Mickaël; Audebert, Stéphane; Rocchi, Stéphane; Giacchero, Damien; Boukari, Fériel; Allegra, Maryline; Chambard, Jean-Claude; Lacour, Jean-Philippe; Michiels, Jean-François; Borg, Jean-Paul; Deckert, Marcel; Tartare-Deckert, Sophie

2015-04-30

Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis.

Extravasation injuries.

PubMed

Rose, R E C; Felix, R; Crawford-Sykes, A; Venugopal, R; Wharfe, G; Arscott, G

2008-01-01

To evaluate the time and type of treatment following extravasation from intravenous infusion and the sequelae of the injuries. The charts of 12 patients who were referred to the Plastic and Orthopaedic Services at the University Hospital of the West Indies were reviewed. The study period was between May 2003 and January 2007. Data were collected on age, gender, site of extravasation, extravasated agent, treatment of the extravasation, necrosis interval, duration of hospital stay for treatment of injury and whether the intravenous line was resited and at what site in relation to the injury. The age of patients ranged from three days to 67 years. The female-to-male ratio was 2:1. In five patients, the intravenous infusion was discontinued immediately after the swelling was noticed. In two patients, the intravenous infusion was stopped after seven hours and in five patients it was discontinued within 12 to 22 hours. The necrosis interval ranged from 12 hours to three weeks. Immediate treatment following extravasation and discontinuation of the infusion included limb elevation in three patients and application of cold compresses in one patient. Eleven patients developed skin necrosis of varying severities. There was no skin necrosis in one patient. Ten patients spent an average of 31 extra days in hospital for treatment of the extravasation injury. Two patients were treated in an out-patient clinic. Extravenous leaks can cause severe tissue injuries. Morbidity is increased by delay in recognition and treatment of the extravasation. A protocol for the treatment of extravasation is recommended.

Management of the extravasation of anti-neoplastic agents.

PubMed

Boulanger, J; Ducharme, A; Dufour, A; Fortier, S; Almanric, K

2015-05-01

Extravasation is a potentially severe complication that can occur during the administration of chemotherapy. The scarcity of evidence available makes it difficult to develop an optimal management scheme. The purpose of this guideline is to review the relevant scientific literature on the prevention, management, and treatment of extravasation occurring during the administration of chemotherapy to cancer patients. A scientific literature review was conducted using the PubMed search tool. The period covered was from database inception to April 2014, inclusively. Since the literature on extravasation treatment is often empirical, anecdotal, and controversial, the review also identified clinical practice guidelines and expert consensuses published by relevant international organizations and cancer agencies. Identification of potential risk factors and preventive measures can reduce the risk of extravasation. Recognition and management of symptoms are crucial in patients with this complication. Provision of adequate instruction to personnel responsible for administering chemotherapy and to patients on recognizing symptoms, preventing, and managing extravasation is essential. Extravasation can be treated with dry warm or cold compresses and various antidotes such as dimethyl sulfoxide, dexrazoxane, hyaluronidase, or sodium thiosulfate, depending on the agent that has caused extravasation. Patient monitoring to assess the progression or regression of symptoms and to thus take the appropriate measures is necessary. Several strategies must be established to ensure that extravasation is recognized and properly managed. Given the evidence available at this time, the Comité de l'évolution des pratiques en oncologie (CEPO) has made recommendations for clinical practice in Quebec.

Microfluidic Device for Studying Tumor Cell Extravasation in Cancer Metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Henry K; Thundat, Thomas George; Evans III, Boyd Mccutchen

Metastasis is the process by which cancer spreads to form secondary tumors at downstream locations throughout the body. This uncontrolled spreading is the leading cause of death in patients with epithelial cancers and is the main reason that suppressing and targeting cancer has proven to be so challenging. Tumor cell extravasation is one of the key steps in cancer s progression towards a metastatic state. This occurs when circulating tumor cells found within the blood stream are able to transmigrate through the endothelium lining and basement membrane of the vasculature to form metastatic tumors at secondary sites within the body.more » Predicting the likelihood of this occurrence in patients, or being able to determine specific markers involved in this process could lead to preventative measures targeting these types of cancer; moreover, this may lead to the discovery of novel anti-metastatic drugs. We have developed a microfluidic device that has shown the extravasation of fluorescently labeled tumor cells across an endothelial cell lined membrane coated with matrigel followed by the formation of colonies. This device provides the advantages of combining a controlled environment, mimicking that found within the body, with real-time monitoring capabilities allowing for the study of these biomarkers and cellular interactions along with other potential mechanisms involved in the process of extravasation.« less

Magnetic forces enable controlled drug delivery by disrupting endothelial cell-cell junctions

NASA Astrophysics Data System (ADS)

Qiu, Yongzhi; Tong, Sheng; Zhang, Linlin; Sakurai, Yumiko; Myers, David R.; Hong, Lin; Lam, Wilbur A.; Bao, Gang

2017-06-01

The vascular endothelium presents a major transport barrier to drug delivery by only allowing selective extravasation of solutes and small molecules. Therefore, enhancing drug transport across the endothelial barrier has to rely on leaky vessels arising from disease states such as pathological angiogenesis and inflammatory response. Here we show that the permeability of vascular endothelium can be increased using an external magnetic field to temporarily disrupt endothelial adherens junctions through internalized iron oxide nanoparticles, activating the paracellular transport pathway and facilitating the local extravasation of circulating substances. This approach provides a physically controlled drug delivery method harnessing the biology of endothelial adherens junction and opens a new avenue for drug delivery in a broad range of biomedical research and therapeutic applications.

Computed tomography contrast media extravasation: treatment algorithm and immediate treatment by squeezing with multiple slit incisions.

PubMed

Kim, Sue Min; Cook, Kyung Hoon; Lee, Il Jae; Park, Dong Ha; Park, Myong Chul

2017-04-01

In our hospital, an adverse event reporting system was initiated that alerts the plastic surgery department immediately after suspecting contrast media extravasation injury. This system is particularly important for a large volume of extravasation during power injector use. Between March 2011 and May 2015, a retrospective chart review was performed on all patients experiencing contrast media extravasation while being treated at our hospital. Immediate treatment by squeezing with multiple slit incisions was conducted for a portion of these patients. Eighty cases of extravasation were reported from approximately 218 000 computed tomography scans. The expected extravasation volume was larger than 50 ml, or severe pressure was felt on the affected limb in 23 patients. They were treated with multiple slit incisions followed by squeezing. Oedema of the affected limb disappeared after 1-2 hours after treatment, and the skin incisions healed within a week. We propose a set of guidelines for the initial management of contrast media extravasation injuries for a timely intervention. For large-volume extravasation cases, immediate management with multiple slit incisions is safe and effective in reducing the swelling quickly, preventing patient discomfort and decreasing skin and soft tissue problems. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Indocyanine green video angiography predicts outcome of extravasation injuries.

PubMed

Haslik, Werner; Pluschnig, Ursula; Steger, Günther G; Zielinski, Christoph C; Schrögendorfer, K F; Nedomansky, Jakob; Bartsch, Rupert; Mader, Robert M

2014-01-01

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention. Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome. The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001). In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.

Extravasation management in the pediatric oncology ward of Children's Hospital of Fudan University: a best practice implementation project.

PubMed

Wang, Yingwen; Kong, Meijing; Ge, Youhong

2016-12-01

Extravasation in a pediatric patient can cause a serious adverse event, but many nurses have insufficient experience to deal with it during intravenous administration. Our division implemented a best practice project, which included extravasation kit instruction preparation, staff education and an update of institutional policy and procedures. The project focused on auditing the extent to which the protocol was implemented and promoting its implementation. The objective of the project was to establish an evidence-based policy and procedure for extravasation management, improve knowledge regarding best practice of extravasation management among staff and formalize the documentation template for extravasation events. The Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice were used to examine compliance with criteria based on the best available evidence before and after the implementation of strategies to promote the use of the evidence-based practice protocol. Four criteria showed a noticeable improvement in compliance: increased use of extravasation kit (0-100%), updated policies and procedure (0-94%), staff education (19-94%) and documented outcomes (13-88%). The project successfully established effective strategies for establishing an extravasation kit instruction sheet, updating policies and procedures, continuous staff education and nursing documentation to ensure best practice and improve patient outcomes.

Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation.

PubMed

Li, Ping-Chia; Shaw, Chen-Fu; Kuo, Tin-Fan; Chien, Chiang-Ting

2005-04-18

The contribution of nitric oxide (NO) to capsaicin-evoked airway responses was investigated in rats. The measurement of plasma NO level, airway dynamics, airway smooth muscle electromyogram, and plasma extravasation by India ink and Evans blue leakage technique was adapted. Capsaicin-evoked hypotension, bronchoconstriction, trachea plasma extravasation as well as increases in plasma NO level in a dose-dependent manner. L-732138 (NK1 receptor antagonist) or SR-48968 (NK2 receptor antagonist) pretreatment reduced capsaicin-enhanced hypotension, bronchoconstriction, plasma extravasation, and plasma NO level. N(G)-nitro-L-Arginine methyl ester (L-NAME, 10 mg/kg, i.v.), a non-selective NO synthase (NOS) inhibitor, or aminoguanidine (10 mg/kg, i.v.), a selective inducible NOS (iNOS) inhibitor, reduced capsaicin-induced increases in plasma NO level and protected against capsaicin-induced plasma extravasation, whereas L-arginine (150 mg/kg, i.v.), a NO precursor, enhanced capsaicin-evoked plasma NO level and plasma extravasation. L-Arginine pretreatment ameliorated capsaicin-induced bronchoconstriction, whereas L-NAME and aminoguanidine exaggerated capsaicin-induced bronchoconstriction. In summary, NK1 and NK2 receptors and iNOS play a role in NO formation and on capsaicin-induced bronchoconstriction and plasma extravasation. NO generated by iNOS counteracts tachykinin-mediated bronchoconstriction, but exacerbates tachykinin-mediated plasma extravasation.

In Vitro Model of Tumor Cell Extravasation

PubMed Central

Jeon, Jessie S.; Zervantonakis, Ioannis K.; Chung, Seok; Kamm, Roger D.; Charest, Joseph L.

2013-01-01

Tumor cells that disseminate from the primary tumor and survive the vascular system can eventually extravasate across the endothelium to metastasize at a secondary site. In this study, we developed a microfluidic system to mimic tumor cell extravasation where cancer cells can transmigrate across an endothelial monolayer into a hydrogel that models the extracellular space. The experimental protocol is optimized to ensure the formation of an intact endothelium prior to the introduction of tumor cells and also to observe tumor cell extravasation by having a suitable tumor seeding density. Extravasation is observed for 38.8% of the tumor cells in contact with the endothelium within 1 day after their introduction. Permeability of the EC monolayer as measured by the diffusion of fluorescently-labeled dextran across the monolayer increased 3.8 fold 24 hours after introducing tumor cells, suggesting that the presence of tumor cells increases endothelial permeability. The percent of tumor cells extravasated remained nearly constant from1 to 3 days after tumor seeding, indicating extravasation in our system generally occurs within the first 24 hours of tumor cell contact with the endothelium. PMID:23437268

Contrast medium extravasation injury: guidelines for prevention and management.

PubMed

Bellin, Marie-France; Jakobsen, Jarl A; Tomassin, Isabelle; Thomsen, Henrik S; Morcos, Sameh K; Thomsen, H S; Morcos, S K; Almén, T; Aspelin, P; Bellin, M F; Clauss, W; Flaten, H; Grenier, N; Ideé, J-M; Jakobsen, J A; Krestin, G P; Stacul, F; Webb, J A W

2002-11-01

Extravasation of contrast material is a well-recognized complication of contrast-enhanced imaging studies. The management of this complication is contentious; therefore, the Contrast Media Safety Committee of The European Society of Urogenital Radiology decided to review the literature and issue guidelines. A comprehensive literature search was carried out. The resulting report was discussed at the 8th European Symposium on Urogenital Radiology in Genoa, Italy. Automated power injection may result in extravasation of large volumes and may or can lead to severe tissue damage. Infants, young children and unconscious and debilitated patients are particularly at risk of extravasation during contrast media injection. Fortunately, most extravasations result in minimal swelling or erythema, with no long-term sequelae; however, severe skin necrosis and ulceration may occur. Large volumes of high osmolar contrast media are known to induce significant tissue damage. Compartment syndrome may be seen associated with extravasation of large volumes. Conservative management is often adequate, but in serious cases the advice of a plastic surgeon is recommended. Based on the review simple guidelines for prophylaxis and management of contrast medium extravasation injuries are proposed.

Extravasation management of nonchemotherapeutic medications.

PubMed

Martin, Sarah M

2013-01-01

Many who think of vesicants think of chemotherapy and oncology patients. But not all vesicants are chemotherapy medications. This article reviews the factors that increase the risk of extravasation, the nonchemotherapeutic medications associated with extravasation injuries, and the recommended treatments.

Effects of N-acetylcysteine and tirilazad mesylate on intestinal functional capillary density, leukocyte adherence, mesenteric plasma extravasation and cytokine levels in experimental endotoxemia in rats.

PubMed

Birnbaum, J; Lehmann, Ch; Klotz, E; Hein, O Vargas; Blume, A; Jubin, F; Polze, N; Luther, D; Spies, C D

2008-01-01

The study's objective was to determine the effects of the administration of N-acetylcysteine (NAC) and of tirilazad mesylate (TM) on intestinal functional capillary density, mesenteric plasma extravasation, leukocyte adherence and on cytokine release during experimental endotoxemia in rats. In a prospective, randomized, controlled animal study, 80 male Wistar rats were examined in 2 test series. Both series were divided into 4 groups. Group 1 served as control group (CON group). Group 2 (LPS group), group 3 (NAC group) and group 4 (TM group) received endotoxin infusions (10 mg/kg over 2 h). In NAC group 150 mg/kg body weight NAC was administered after the first 30 minutes of endotoxemia intravenously. In TM group, 10 mg/kg body weight TM was administered after the first 30 minutes of endotoxemia intravenously. Animals of the series 1 underwent studies of leukocyte adherence on submucosal venular endothelium of the small bowel wall and intestinal functional capillary density (FCD) in the intestinal mucosa and the circular as well as the longitudinal muscle layer by intravital fluorescence microscopy (IVM). Plasma levels of interleukin 1beta (IL-1beta), interferone gamma (IFN-gamma) and soluble intercellular adhesion molecule1 (s-ICAM 1) as well as white blood cell count (WBC) were estimated. In the animals of the series 2 mesenteric plasma extravasation was determined by IVM and plasma levels of tumor necrosis factor alpha (TNF-alpha), IL-4, IL-6, IL-10 and malondialdehyde (MDA) were estimated. After LPS administration, FCD in the villi intestinales was unchanged and in the longitudinal muscularis layer it was increased. There was no effect of NAC or TM administration on FCD.Although the plasma extravasation was not significantly influenced by LPS administration, TM administration resulted in a lower plasma extravasation in the TM group compared to the other groups. After endotoxin challenge, the firmly adherence of leukocytes to vascular endothelium as a parameter of leukocyte activation in endotoxemia was increased but NAC or TM administration had no influence on leukocyte adherence. The plasma levels of IL-1beta, IL-6, IL-10, TNF-alpha, IFN-gamma and sICAM-1 were increased in the endotoxemic groups (LPS group, NAC group and TM group) and the WBC was decreased compared to controls. IL-4 levels were unchanged during observation period. Plasma MDA levels were not influenced by LPS administration compared to controls. The administration of NAC resulted in lower sICAM-1 and MDA levels compared to the LPS group. The IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma plasma levels were not influenced by NAC or TM administration. In this posttreatment sepsis model in rats, NAC administration resulted in lower sICAM-1 and MDA levels compared to the LPS treated animals. TM administration reduced the plasma extravasation in this model.

Port-a-Cath extravasation of vesicant cytotoxics: surgical options for a rare complication of cancer chemotherapy.

PubMed

Haslik, W; Hacker, S; Felberbauer, F X; Thallinger, C; Bartsch, R; Kornauth, C; Deutschmann, C; Mader, R M

2015-03-01

Although implantation of a central venous device such as a Port-a-Cath was initially considered safe, extravasation rates up to 4.7% have been reported. Therefore, the objective of this study was to propose a structured procedure for the management of extravasation of a cytotoxic treatment. A total of eight patients were evaluated after port extravasation of epirubicin (n = 3), platinum compounds (n = 3), paclitaxel (n = 1), or trabectedin (n = 1) into the subcutaneous space. Immediate explantation of the port was performed in combination with a "Subcutaneous Wash-Out Procedure" (SWOP). When removal of the port was delayed, débridement and flap coverage were performed as necessary. Epirubicin concentrations present in the samples obtained during surgical intervention were subsequently analysed using high-performance liquid chromatography (HPLC). Patients were followed for at least six months and were examined for sequelae such as pain, induration, redness, and limited movement. All three patients whose extravasation event was detected during chemotherapy administration benefited from SWOP with acceptable side effects (e.g., erythema). The analysis of epirubicin concentrations demonstrated the active removal of relevant amounts of the compound by wound rinsing. In contrast, late detection of extravasation led to major débridement and flap coverage in four out of five patients. A high body mass index (BMI) value was associated with all of the patients that experienced port extravasation. Depending on when Port-a-Cath extravasations into subcutaneous tissue are detected, different treatments are appropriate. When extravasation is detected early, the SWOP was found to be beneficial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia.

PubMed

Li, Li; ten Hagen, Timo L M; Bolkestein, Michiel; Gasselhuber, Astrid; Yatvin, Jeremy; van Rhoon, Gerard C; Eggermont, Alexander M M; Haemmerich, Dieter; Koning, Gerben A

2013-04-28

Accumulation of nanoparticles in solid tumors depends on their extravasation. However, vascular permeability is very heterogeneous within a tumor and among different tumor types, hampering efficient delivery. Local hyperthermia at a tumor can improve nanoparticle delivery by increasing tumor vasculature permeability, perfusion and interstitial fluid flow. The aim of this study is to investigate hyperthermia conditions required to improve tumor vasculature permeability, subsequent liposome extravasation and interstitial penetration in 4 tumor models. Tumors are implanted in dorsal skin flap window chambers and observed for liposome (~85 nm) accumulation by intravital confocal microscopy. Local hyperthermia at 41°C for 30 min initiates liposome extravasation through permeable tumor vasculature in all 4 tumor models. A further increase in nanoparticle extravasation occurs while continuing heating to 1h, which is a clinically relevant duration. After hyperthermia, the tumor vasculature remains permeable for 8h. We visualize gaps in the endothelial lining of up to 10 μm induced by HT. Liposomes extravasate through these gaps and penetrate into the interstitial space to at least 27.5 μm in radius from the vessel walls. Whole body optical imaging confirms HT induced extravasation while liposome extravasation was absent at normothermia. In conclusion, a thermal dose of 41°C for 1h is effective to induce long-lasting permeable tumor vasculature for liposome extravasation and interstitial penetration. These findings hold promise for improved intratumoral drug delivery upon application of local mild hyperthermia prior to administration of nanoparticle-based drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Involvement of the TRPV1 receptor in plasma extravasation in airways of rats treated with an angiotensin-converting enzyme inhibitor.

PubMed

de Oliveira, Janiana Raíza Jentsch Matias; Otuki, Michel Fleith; Cabrini, Daniela Almeida; Brusco, Indiara; Oliveira, Sara Marchesan; Ferreira, Juliano; André, Eunice

2016-12-01

Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of hypertension, congestive heart failure and renal disease, and are considered relatively safe and generally well-tolerated drugs. However, adverse effects of ACEIs have been reported, including non-productive cough and angioedema, which can lead to poor adherence to therapy. The mechanisms by which ACEIs promote adverse effects are not fully elucidated, although increased bradykinin plasma levels following ACEI therapy seem to play an important role. Since bradykinin can sensitise the transient potential vanilloid receptor 1 (TRPV1), we investigated the role of TRPV1 in plasma extravasation in the trachea and bronchi of rats treated with the ACEI captopril. We observed that intravenous (i.v.) administration of captopril did not cause plasma extravasation in the trachea or bronchi of spontaneously breathing rats, but induced plasma extravasation in the trachea and bronchi of artificially ventilated rats. The intratracheal (i.t.) instillation of capsaicin or bradykinin also induced an increase in plasma extravasation in the trachea and bronchi of artificially ventilated rats. As expected, capsaicin-induced plasma extravasation was inhibited by i.t. pretreatment with the TRPV1 selective antagonist capsazepine (CPZ) while bradykinin-induced plasma extravasation was reduced by i.t. pretreatment with the selective B 2 receptor antagonist Icatibant, originally known as HOE 140 (HOE). Interestingly, bradykinin-induced plasma extravasation was also inhibited by CPZ. The pretreatment with HOE and CPZ, singly or in combination and at doses which do not cause inhibitory effects per se, significantly inhibited the plasma extravasation induced by captopril treatment in artificially ventilated rats. In addition, treatment with a high dose of capsaicin in newborn rats, which induces degeneration of TRPV1-expressing sensory neurons, abolished both capsaicin and captopril-induced plasma extravasation in artificially ventilated rats. In conclusion, our study identified that captopril treatment promoted sensitisation of TRPV1, via B 2 receptor activation, inducing plasma extravasation in the airways of mechanically ventilated rats. The present findings add a new view about the role of TRPV1 in the plasma extravasation induced by captopril and could to contribute to the elucidation of mechanisms by which ACEI induces adverse effects on airways. Copyright © 2016 Elsevier Ltd. All rights reserved.

Extravasation injuries: current medical and surgical treatment.

PubMed

Doornaert, M; Monstrey, S; Roche, N

2013-01-01

Extravasation is a devastating complication of intravenous therapy that develops when a drug infiltrates the interstitial tissue surrounding the vein. Due to the uncertain and possibly dramatic outcome, early recognition and adequate treatment with the aid of a standardized protocol are needed. A pubmed literature search was conducted and all relevant articles were reviewed for the development of an extravasation treatment protocol. An overview of current treatment guidelines and clinical experience is provided. The extravasation treatment protocol was implied during 1 year in this university hospital with satisfactory outcome. Treatment starts with prevention. In case of an established extravasation injury, early recognition, assessment of severity, and treatment with medical and/or surgical therapies are recommended.

Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation.

PubMed

Kingery, W S; Guo, T; Agashe, G S; Davies, M F; Clark, J D; Maze, M

2001-09-21

Sciatic nerve section in rats evokes chronic limb edema, pain behavior, and hindpaw hyperalgesia, a syndrome resembling the complex regional pain syndrome type II (CRPS II or causalgia) in man. Glucocorticoids such as methylprednisolone (MP) have been used as analgesic and anti-edematous agents in patients suffering from CRPS, and interestingly these therapeutic effects appear to persist in some patients after stopping the medication. Similar to the CRPS clinical response to glucocorticoids, we now demonstrate that chronic hindpaw edema in the sciatic transection CRPS model is reversed by a continuous infusion of MP (3 mg/kg/day over 21 days), and this anti-edematous effect persists for at least 1 week after discontinuing MP. Furthermore, there is a chronic increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous hands of CRPS patients. A 2-week infusion of MP (3 mg/kg/day) reduced spontaneous protein extravasation in the hindpaw skin by 80%. We postulated that increased spontaneous neurogenic extravasation resulted in development of limb edema in both the animal model and the CRPS patient, and that the anti-edematous effects of MP are due to an inhibition of spontaneous extravasation. Additional experiments examined the inhibitory effects of MP infusion on electrically-evoked neurogenic extravasation in the hindpaw skin of normal rats. MP inhibition was dose- and time-dependent, with an ED(50) of 1.2 mg/kg/day for a 14-day continuous infusion of MP, and a maximum inhibitory effect requiring 17 days of MP infusion (3 mg/kg/day). MP (3 mg/kg/day for 14 days) also blocked both capsaicin- and SP-evoked neurogenic extravasation, indicating a post-junctional inhibitory effect. Our interpretation is that increased spontaneous neurogenic extravasation in this CRPS model contributed to the development and maintenance of hindpaw edema, and that chronic MP administration dose- and time-dependently blocked neurogenic extravasation at a post-junctional level, thus reversing spontaneous extravasation and limb edema in this model.

Airway extravasation induced by increasing airway temperature in ovalbumin-sensitized rats

PubMed Central

Hsu, Chun-Chun; Tapia, Reyno J.; Lee, Lu-Yuan

2015-01-01

This study was carried out to determine whether hyperventilation of humidified warm air (HWA) induced airway extravasation in ovalbumin (Ova)-sensitized rats. Our results showed: 1) After isocapnic hyperventilation with HWA for 2 min, tracheal temperature (Ttr) was increased to 40.3°C, and the Evans blue contents in major airways and lung tissue were elevated to 651% and 707%, respectively, of that after hyperventilation with humidified room air in Ova-sensitized rats; this striking effect of HWA was absent in control rats. 2) The HWA-induced increase in Evans blue content in sensitized rats was completely prevented by a pretreatment with either L-732138, a selective antagonist of neurokinin type 1 (NK-1) receptor, or formoterol, a selective agonist of β2 adrenoceptor. This study demonstrated that an increase in airway temperature induced protein extravasation in the major airways and lung tissue of sensitized rats, and an activation of the NK-1 receptor by tachykinins released from bronchopulmonary C-fiber nerve endings was primarily responsible. PMID:25864799

Effect of α-trinositol on interstitial fluid pressure, oedema generation and albumin extravasation in experimental frostbite in the rat

PubMed Central

Berg, A; Aas, P; Gustafsson, T; Reed, R K

1999-01-01

The anti-inflammatory effect of α-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. α-Trinositol (40 mg kg body weight−1) was administered intravenously as a bolus both before and/or in the interval between freezing and thawing of the tissue. Pif was measured in rat paw skin with micropipettes connected to a servo-controlled counterpressure system. Oedema formation was estimated by measuring the increase in total tissue water content (wet weight minus dry weight divided by dry weight). Albumin extravasation (i.e., the difference between the plasma equivalent space for 125I- and 131I-human serum albumin (HSA) circulating for different time intervals) was used to estimate the microvascular leakage. Compared to untreated animals, α-trinositol given pre- and/or post-freeze reduced total tissue water and albumin extravasation as well as the fall in Pif in injured tissue significantly (P<0.05). α-Trinositol given only post-freeze reduced total tissue water and albumin extravasation from 4.46±0.93 and 2.37±1.12 to 2.51±0.29 and 0.36±0.18 ml g dry weight−1, respectively (P<0.05). Pif fell from −0.8±0.2 mmHg pre-freeze to −3.4±1.0 mmHg (P<0.05) at 20 min after tissue injury (circulatory arrest) and was attenuated by treatment with α-trinositol. We conclude that α-trinositol exerts its anti-oedematous effect by acting on the extracellular matrix, attenuating the lowering of Pif as well as on the microvascular wall, thereby decreasing the protein extravasation. PMID:10217530

Radiocontrast Dye Extravasation During Sialography.

PubMed

Truong, Kristy; Hoffman, Henry T; Policeni, Bruno; Maley, Joan

2018-03-01

Evaluate the pathophysiology of contrast extravasation. Two hundred fifty-five sialograms at the University of Iowa from 2008 to 2016 were reviewed. Twelve sialograms (4.7% of total) were identified with main ductal extravasation. In each case, ductal stenosis as a diagnosis was supported by clinical history and the finding of difficulty in advancing the cannula into the duct during sialography. In all but 1 case, extravasation occurred at the distal duct with no further imaging of the ductal system. Each of the 5 cases treated with sialendoscopy with or without gland resection confirmed stenosis. Ultrasound evaluation of 5 of the cases detected ductal dilation in 4 (80%). Six of 11 computed tomography scans done before the sialogram were interpreted as normal with indirect evidence for ductal stenosis (duct dilation) reported in only 1. All extravasations were associated with either stricture alone or stricture with stone (1 case). Radiocontrast extravasation from the main duct during sialography is highly associated with the presence of ductal stricture. In our experience, the inability to fill the ductal system with radiocontrast is a useful sialographic finding that correlated closely with anatomic abnormality rather than technical error. The frequent finding of extravasation of radiocontrast supports the use of water soluble contrast.

Radioscintigraphic demonstration of unsuspected urine extravasation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bocchini, T.; Williams, W.; Patton, D.

Three cases of unsuspected urine extravasation first detected by radionuclide scintigraphy are presented with subsequent confirmation by CT and, retrograde pyelograms. A renal study done to rule out acute transplant rejection demonstrates gallbladder uptake which was initially thought to be consistent with urine extravasation.

Extravasation: prevention, recognition and management.

PubMed

Dougherty, Lisa

This article provides readers with an overview of extravasation, including risk factors and management strategies. The importance of accurate reporting and documentation is also highlighted, particularly as patients will often require follow-up care and may take legal action as a result of extravasation injury.

Extravasation of radiographic contrast media: prevention, diagnosis, and treatment.

PubMed

Tonolini, Massimo; Campari, Alessandro; Bianco, Roberto

2012-01-01

Contrast media extravasation represents a not unusual problem in radiological practice. Incidence, patient-, and procedure-related risk factors, pathogenesis, and clinical manifestations of extravasation injuries are discussed with a review of recent literature, and a practical preventive approach is proposed. A diagnostic and therapeutic protocol, to be applied whenever contrast extravasation is detected, includes radiographic assessment of compartmentalization, antidote application, local care, and clinical follow-up; indications for surgical consultation and adverse event reporting are provided. Copyright © 2012 Mosby, Inc. All rights reserved.

Extravasation of Noncytotoxic Drugs: A Review of the Literature.

PubMed

Le, Ann; Patel, Samit

2014-07-01

Extravasation is a potential complication associated with intravenous therapy administration. Inadvertent leakage of medications with vesicant properties can cause severe tissue necrosis, which can lead to devastating long-term consequences. Recognizing potential agents is an essential step in mitigating the risk of extravasation. A literature search was carried out using PubMed with the following key words: extravasation, soft tissue injury, phlebitis, and infiltration, from January 1961 through January 2014. The publications were screened manually and reviewed to identify reports for medications that included synonyms of the International Nonproprietary Name, while excluding antineoplastic agents, radiographic contrast material, investigational or nonmarketed drugs, and animal data, to yield 70 articles. Furthermore, reference citations from publications were also reviewed for relevance and yielded 4 articles. We discovered 232 cases of extravasation involving 37 agents (in order of frequency): phenytoin, parenteral nutrition, calcium gluconate, potassium chloride, calcium chloride, dopamine, dextrose solutions, epinephrine, sodium bicarbonate, nafcillin, propofol, norepinephrine, mannitol, arginine, promethazine, vancomycin, tetracycline, dobutamine, vasopressin, sodium thiopental, acyclovir, amphotericin, ampicillin, cloxacillin, gentamicin, metronidazole, oxacillin, penicillin, amiodarone, albumin, furosemide, lipids, lorazepam, immunoglobulin, morphine, and sodium valproate. Potential properties contributing to extravasation include the following: pH, osmolarity, diluent, vasoactive properties, and inactive ingredients. Antidotes and supportive care agents used in the management of these cases of extravasation include hyaluronidase, phentolamine, terbutaline, topical anesthetics (such as lidocaine and prilocaine cream), topical antimicrobials (such as silver sulfadiazine and chlorhexidine), topical debridement agents (collagenase ointment), topical steroids, and topical vasodilators (nitroglycerin). Data on the management of noncytotoxic extravasations is sparse, consisting primarily of case reports and anecdotal evidence. Fortunately, this adverse outcome is preventable and identification of vesicant agents plays a pivotal role. The intent of this review is to provide a reference identifying noncytotoxic vesicants and the management of extravasations associated with specific agents. © The Author(s) 2014.

Extravasation of adhering vesicles

NASA Astrophysics Data System (ADS)

Tordeux, C.; Fournier, J.-B.

2002-12-01

We study how the passage of lipid vesicles through a small pore can be induced by the difference in non-specific adhesion energy between the two sides of the substrate bearing the pore. This process is inspired from the extravasation of cells or liposomes from blood vessels, which involves adhesion binders. We study the adhesion-dominated regime and we show that the passage of a vesicle of volume V and area A is selective in terms of the reduced volume v ~ V/A3/2. Extravasation occurs for adhesion ratios of order unity. We also consider the possibility of pressure-induced extravasation in the presence of adhesion. Finally, we propose a micro-device based on adhesion-induced extravasation, which is designed to sort vesicles according to their deflatedness.

Cervical extravasation of bevacizumab.

PubMed

Dréanic, Johann; Coriat, Romain; Mir, Olivier; Perkins, Géraldine; Boudou-Rouquette, Pascaline; Brezault, Catherine; Dhooge, Marion; Goldwasser, François; Chaussade, Stanislas

2013-04-01

Monoclonal antibodies such as bevacizumab are widely used in medical oncology, either alone or in combination with chemotherapy. No specific recommendations on the management of monoclonal antibodies extravasation exist. Incidence rates vary considerably. Estimates of 0.5-6% have been reported in the literature. Also, patient-associated and procedure-associated risk factors of extravasation are multiple, such as bolus injections or poorly implanted central venous access. We report on an 86-year-old woman with colon cancer with liver metastasis who was treated with 5-fluorouracil, folinic acid, and bevacizumab. Extravasation occurred during chemotherapy infusion because of a catheter migration of the port outside of the superior vena cava, causing cervical pain without skin modifications. Diagnosis was confirmed with the appearance of clinical right cervical tumefaction and cervicothoracic computed tomography scan indicated a perijugular hypodense collection, corresponding to the extravasation. Conservative management was proposed. The patient recovered within 3 weeks from all symptoms. Physicians should be aware that in cases of bevacizumab extravasation, a nonsurgical approach might be effective.

[Cutaneous pigmentation related to intravenous iron extravasation: Analysis from the French pharmacovigilance database].

PubMed

Hermitte-Gandoliere, Alexia; Petitpain, Nadine; Lepelley, Marion; Thomas, Laure; Le Beller, Christine; Astoul, Jacqueline Ponte; Gillet, Pierre

Intravenous iron infusion may be complicated by extravasation and lead to cutaneous pigmentation. We queried the French pharmacovigilance database to assess the spontaneously reported cases over the 2000-2016 period. Fifty-one cases of cutaneous pigmentation related to intravenous iron extravasation were retrieved, none was associated to necrosis. Most of patients were women aged 20 to 49 years old. The pigmentation was mostly a brown coloration, persisting over one month in 19 cases (37.2%) and over 6 months in 9 cases (17.6%). The management of extravasation and pigmentation was heterogeneous and was rarely followed by a decrease of the coloration. Cutaneous pigmentation after intravenous iron extravasation can persist over time and create an aesthetic prejudice, particularly in young women. Standardized extravasation and iron-induced pigmentation management procedures appear necessary. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Topical local anaesthetics (EMLA) inhibit burn-induced plasma extravasation as measured by digital image colour analysis.

PubMed

Jönsson, A; Mattsson, U; Tarnow, P; Nellgård, P; Cassuto, J

1998-06-01

Amide local anaesthetics have previously been shown to reduce oedema and improve dermal perfusion following experimental burns. Previous studies have used invasive techniques for burn oedema quantification which do not allow continuous monitoring in the same animal. The present study used digital image colour analysis to investigate the effect of topical local anaesthetics on burn-induced extravasation of Evans blue albumin. A standardised full-thickness burn injury (1 x 1 cm) was induced in the abdominal skin of anaesthetised rats. The burn area was subsequently covered with 0.5 g of lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA, ASTRA, Sweden) or placebo cream during the first hour post-burn. One hour after the burn trauma, animals received Evans blue dye intravenously. Skin colour appearances were recorded by macrophotography before the burn and 5, 60. 65, 90, 120, 150, and 180 min post-burn. Colour slides were digitised and colour changes were analysed using the normalised red-green-blue (n-rgb) colour system. Results showed a significant inhibition of Evans blue extravasation between 60 and 180 min post-burn in EMLA-treated animals versus controls. Topical local anaesthetics are potent inhibitors of burn-induced plasma albumin extravasation, probably by direct action on vascular permeability and by inhibition of various steps of the pathophysiological response after burn injury.

Extravasation of calcium solution leading to calcinosis cutis surrounding the dorsal cutaneous branch of the ulnar nerve.

PubMed

Tuncer, S; Aydin, A; Erer, M

2006-06-01

A case of calcinosis cutis caused by calcium extravasation around the wrist is presented. During excision, the lesion was seen to be surrounding the dorsal branch of the ulnar nerve. The possibility of peripheral nerve involvement in extravasation injuries is emphasized.

Radionuclide demonstration of urinary extravasation with ureteral obstruction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeh, V.A.; Chiang, L.C.; Meade, R.C.

Two cases of urinary extravasation with ureteral obstruction demonstrated by the radionuclide studies are reported. The value of radionuclide studies in patients with renal transplantation has been reported previously, but studies in patients without transplantation have rarely been described in the literature. Ureteral obstruction may cause urinary extravasation, which may be demonstrated by radionuclide studies even when radiologic studies are inconclusive. In one case, urinary extravasation was detected in the sitting position but not in the supine position. Renal imaging should probably be performed not only with multiple projections but also in different positions.

Shape Matters: Intravital Microscopy Reveals Surprising Geometrical Dependence for Nanoparticles in Tumor Models of Extravasation

PubMed Central

Smith, Bryan Ronain; Kempen, Paul; Bouley, Donna; Xu, Alexander; Liu, Zhuang; Melosh, Nicholas; Dai, Hongjie; Sinclair, Robert; Gambhir, Sanjiv Sam

2012-01-01

Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous. PMID:22650417

Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation

PubMed Central

Cheng, Chih-Chung; Yang, Ya Lan; Liao, Kate Hsiurong; Lai, Ted Weita

2016-01-01

Conventional methods for therapeutic blood-brain barrier (BBB) disruption facilitate drug delivery but are cumbersome to perform. A previous study demonstrated that adenosine receptor (AR) stimulation by 5′-N-ethylcarboxamide adenosine (NECA) increased the extravasation of intravascular tracers into the brain and proposed that AR agonism may be an effective method for therapeutic BBB disruption. We attempted to confirm the extravasation of tracers into the brain and also investigated tracer extravasation into peripheral organs and tracer retention in the blood. We found that NECA not only increased the extravasation of intravascular fluorescein and low molecular weight dextran into the brain of mice but also increased the concentrations of these tracers in the blood. In fact, the brain:blood ratio-normalized BBB permeability for either tracer is actually decreased by NECA administration. Elevated blood urea nitrogen levels in mice following NECA treatment suggested that renal function impairment was a probable cause of tracer retention. Therefore, NECA has almost no effect on the extravasation of intravascular Evans blue dye (EBD), an albumin-binding tracer with little renal clearance. Rather than inducing BBB disruption, our study demonstrated that NECA increased tracer extravasation into the brain by increasing the concentration gradient of the tracer across the BBB. PMID:27025761

Younger age and in situ duration of peripheral intravenous catheters were risk factors for extravasation in a retrospective paediatric study.

PubMed

Fonzo-Christe, C; Parron, A; Combescure, C; Rimensberger, P C; Pfister, R E; Bonnabry, P

2018-07-01

Epidemiological data on the incidence and risk factors of extravasation of peripheral intravenous catheters (PIVC) in neonates and children are scarce and that is what this study explored. This was a one-year retrospective study of all neonates and paediatric intensive care patients with at least one recorded PIVC at the Geneva University Hospitals, Switzerland, in 2013. The extravasation rate was determined for all patients, including neonates below 28 days, and for all PIVCs. Multivariate analysis of the associated risk factors was performed. We analysed 1300 PIVC in 695 paediatric patients with a median age of 1.5 years. The overall extravasation incidence was 17.6% for all patients and 11.7% for PIVC. The overall incidence rate of PIVC extravasation was 4.5 per 100 catheters days, and the risk was highest in the 201 neonates, at 28.4%. The incidence rate four days after insertion of the PIVC was around three times higher than on day one. Neonates and the in situ duration of PIVCs were associated risk factors (p < 0.001). Extravasation was frequent and neonates were particularly at risk. Younger age and longer in situ PIVC duration were independent risk factors for extravasation. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Pharmacological management of anticancer agent extravasation: A single institutional guideline.

PubMed

Kimmel, Jaime; Fleming, Patrick; Cuellar, Sandra; Anderson, Jennifer; Haaf, Christina Mactal

2018-03-01

Although the risk of extravasation of a chemotherapy (anticancer) medication is low, the complications associated with these events can have a significant impact on morbidity and health care costs. Institutions that administer anticancer agents should ideally have a current guideline on the proper management of the inadvertent administration of these toxic medications into tissues surrounding blood vessels. It is imperative that the health care team involved in administering drugs used to treat cancer be educated on the risk factors, preventative strategies and treatment of anticancer extravasations, as well as practice safe and proper administration techniques. Anticancer agents are generally divided into classes based on their ability to cause tissue damage. The review of current published guidelines and available literature reveals a lack of consensus on how these medications should be classified. In addition, many recently approved drugs for the treatment of cancer may lack data to support their classification and management of extravasation events. The treatment of the majority of extravasations of anticancer agents involves nonpharmacological measures, potentially in the ambulatory care setting. Antidotes are available for the extravasation of a minority of vesicant agents in order to mitigate tissue damage. Due to the limited data and lack of consensus in published guidelines, a working group was established to put forth an institutional guideline on the management of anticancer extravasations.

Adenosine receptor agonist NECA increases cerebral extravasation of fluorescein and low molecular weight dextran independent of blood-brain barrier modulation.

PubMed

Cheng, Chih-Chung; Yang, Ya Lan; Liao, Kate Hsiurong; Lai, Ted Weita

2016-03-30

Conventional methods for therapeutic blood-brain barrier (BBB) disruption facilitate drug delivery but are cumbersome to perform. A previous study demonstrated that adenosine receptor (AR) stimulation by 5'-N-ethylcarboxamide adenosine (NECA) increased the extravasation of intravascular tracers into the brain and proposed that AR agonism may be an effective method for therapeutic BBB disruption. We attempted to confirm the extravasation of tracers into the brain and also investigated tracer extravasation into peripheral organs and tracer retention in the blood. We found that NECA not only increased the extravasation of intravascular fluorescein and low molecular weight dextran into the brain of mice but also increased the concentrations of these tracers in the blood. In fact, the brain:blood ratio-normalized BBB permeability for either tracer is actually decreased by NECA administration. Elevated blood urea nitrogen levels in mice following NECA treatment suggested that renal function impairment was a probable cause of tracer retention. Therefore, NECA has almost no effect on the extravasation of intravascular Evans blue dye (EBD), an albumin-binding tracer with little renal clearance. Rather than inducing BBB disruption, our study demonstrated that NECA increased tracer extravasation into the brain by increasing the concentration gradient of the tracer across the BBB.

Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: a prospective clinical study.

PubMed

Bertelli, G; Gozza, A; Forno, G B; Vidili, M G; Silvestro, S; Venturini, M; Del Mastro, L; Garrone, O; Rosso, R; Dini, D

1995-11-01

To evaluate the activity and tolerability of dimethylsulfoxide (DMSO) in the prevention of soft tissue toxicity after extravasation of cytotoxic drugs. From June 1991 to December 1994, all patients who had an extravasation during intravenous (IV) infusion of cytotoxic drugs in our institution were considered for an open, prospective study of preventive treatment with 99% DMSO, applied topically on the extravasation site every 8 hours for 7 days. Intermittent local cooling (for 1 hour three times daily) on the first 3 days was also used. One hundred forty-four patients with extravasations of doxorubicin (n = 11), epirubicin (n = 46), mitomycin (n = 5), mitoxantrone (n = 13), cisplatin (n = 44), carboplatin (n = 6), ifosfamide (n = 14), and fluorouracil (n = 5) entered the study; 127 were assessable. Only one patient suffered an ulceration. The treatment was well tolerated, with mild local burning and a characteristic breath odor being the only side effects of DMSO application, even in cases in which treatment continued for up to 6 weeks to obtain remission of the symptoms of extravasation. Topical DMSO is an effective and safe antidote that may be used with local cooling after extravasations of vesicant drugs other than those drugs for which standard interventions are defined.

Effect of the Location of Endplate Cement Extravasation on Adjacent Level Fracture in Osteoporotic Patients Undergoing Vertebroplasty and Kyphoplasty.

PubMed

Jesse, Mary Kristen; Petersen, Brian; Glueck, Deborah; Kriedler, Sarah

2015-01-01

The most widely researched risk/complication following vertebroplasty (VP) or kyphoplasty (KP) is that of adjacent level fracture (ALF). Current literature results regarding the effect of intradiscal extravasation of cement on the risk of ALF is conflicting with about half of the studies concluding there is no added risk with endplate extravasation and half of the studies reporting opposite conclusions. The purpose of the study is to further stratify the data to determine whether specifically the location and extent of endplate cement extravasation more strongly affect ALF risk in osteoporotic patients following either VP or balloon KP. Retrospective cohort study. University teaching hospital. One hundred and fifty-six cemented levels in 80 patients, treated at a single center between 2008 and 2012 were reviewed. Age, gender, T-score, body mass index, and osteoporosis type (primary or secondary) were recorded. An ALF was defined as a fracture: 1) in a non-cemented vertebra; 2) adjacent to a cemented level; and 3) not due to trauma or malignancy. Location of the cement extravasation (anterior, middle, or posterior third of the vertebral body) and extravasation extent (percentage of the intervertebral disc height occupied by the bolus) were measured. A logistic modeling strategy permitted examining the association between the location and extent of extravasation and the odds of ALF. ALF occurred in 14 of the 52 patients (27%) and 20 of the 98 levels (20.4%) remaining after exclusions. Odds of ALF were 5.9 times higher (95% CI: 1.6 to 21.2, P = 0.008) with extravasation when compared to no leakage. Odds of ALF in a given patient were 22.6 times higher (95% CI: 3.0 to 170.9, P = 0.003) with anterior extravasation when compared to no leakage. Leakage in the middle or posterior thirds and extent of extravasation were not associated with ALF. Limitations of the study include the retrospective study design and small sample size as well as the retrospective implementation of follow-up criteria posing risk of selection bias. Cement endplate extravasation isolated to the anterior third of the vertebral body is associated with is significantly higher odds of ALF after VP or KP in patients with osteoporosis.

Describing Intravenous Extravasation in Children (DIVE Study).

PubMed

Paquette, Vanessa; McGloin, Rumi; Northway, Tracie; Dezorzi, Pia; Singh, Avash; Carr, Roxane

2011-09-01

Extravasation, the inadvertent leakage of intravenous (IV) medication from the vein into the surrounding tissue, is a iatrogenic cause of patient injury. Extravasation has been reported to occur in 0.1% to 6.5% of hospital inpatients. The incidence may be higher among children because they have multiple risk factors, including small and fragile veins, decreased peripheral circulation, capillary leakage, and flexible subcutaneous tissue. To describe the incidence of extravasation at a pediatric tertiary care hospital, to identify the agents causing extravasation, and to describe the use of antidotes to manage identified cases. A secondary objective was to describe adverse drug effects associated with the antidotes administered. The medical records of pediatric patients with documented extravasation of an IV medication between January 1, 2006, and August 31, 2008, were analyzed retrospectively. The appropriateness of antidote use was determined in terms of adherence to the institution's protocol for treatment of extravasation. A total of 42 patients had documented extravasation, for an overall incidence of 0.04% per patient-day. Of the 40 cases in which location was documented, 12 (30%) occurred on the general pediatric wards, 10 (25%) on the surgical ward, 9 (22%) in the neonatal intensive care unit, 5 (12%) in the pediatric intensive care unit, 3 (8%) in day care, and 1 (2%) in the emergency department. The most common medications involved were fluids for IV administration (18 [43%]), potassium chloride (11 [26%]), antibiotics (8 [19%]), total parenteral nutrition (8 [19%]), calcium chloride (2 [5%]), and epinephrine (2 [5%]). Multiple drugs were involved in some cases of extravasation. The decision to administer an antidote and the choice of antidote (if required) were appropriate in 50% of the cases. No adverse drug effects were reported with use of antidotes. The incidence of extravasation was low. The medications most commonly involved were similar to those reported in the literature. Antidotes were well tolerated but were appropriately used in only half of the events. Prospective trials are needed to determine the clinical severity of injury and to assess the effectiveness and safety of antidotes.

Describing Intravenous Extravasation in Children (DIVE Study)

PubMed Central

Paquette, Vanessa; McGloin, Rumi; Northway, Tracie; DeZorzi, Pia; Singh, Avash; Carr, Roxane

2011-01-01

Background: Extravasation, the inadvertent leakage of intravenous (IV) medication from the vein into the surrounding tissue, is a iatrogenic cause of patient injury. Extravasation has been reported to occur in 0.1% to 6.5% of hospital inpatients. The incidence may be higher among children because they have multiple risk factors, including small and fragile veins, decreased peripheral circulation, capillary leakage, and flexible subcutaneous tissue. Objectives: To describe the incidence of extravasation at a pediatric tertiary care hospital, to identify the agents causing extravasation, and to describe the use of antidotes to manage identified cases. A secondary objective was to describe adverse drug effects associated with the antidotes administered. Methods: The medical records of pediatric patients with documented extravasation of an IV medication between January 1, 2006, and August 31, 2008, were analyzed retrospectively. The appropriateness of antidote use was determined in terms of adherence to the institution’s protocol for treatment of extravasation. Results: A total of 42 patients had documented extravasation, for an overall incidence of 0.04% per patient-day. Of the 40 cases in which location was documented, 12 (30%) occurred on the general pediatric wards, 10 (25%) on the surgical ward, 9 (22%) in the neonatal intensive care unit, 5 (12%) in the pediatric intensive care unit, 3 (8%) in day care, and 1 (2%) in the emergency department. The most common medications involved were fluids for IV administration (18 [43%]), potassium chloride (11 [26%]), antibiotics (8 [19%]), total parenteral nutrition (8 [19%]), calcium chloride (2 [5%]), and epinephrine (2 [5%]). Multiple drugs were involved in some cases of extravasation. The decision to administer an antidote and the choice of antidote (if required) were appropriate in 50% of the cases. No adverse drug effects were reported with use of antidotes. Conclusions: The incidence of extravasation was low. The medications most commonly involved were similar to those reported in the literature. Antidotes were well tolerated but were appropriately used in only half of the events. Prospective trials are needed to determine the clinical severity of injury and to assess the effectiveness and safety of antidotes. PMID:22479086

Clinical outcome and subsequent sequelae of cement extravasation after percutaneous kyphoplasty and vertebroplasty: a comparative review.

PubMed

Semaan, Hassan; Obri, Tawfik; Bazerbashi, Mohamad; Paull, Daniel; Liu, Xiaochen; Sarrouj, Marah; Elgafy, Hossein

2018-07-01

Background Injection of cement during vertebroplasty and kyphoplasty can leak into surrounding structures and could be symptomatic. Purpose To identify the sites and incidence of cement extravasation after kyphoplasty and vertebroplasty, and to evaluate their impacts on clinical outcomes. Material and Methods A retrospective review of 316 patients treated with kyphoplasty and vertebroplasty; 411 cases were included (223 kyphoplasty and 188 vertebroplasty). Cement extravasation was evaluated postoperatively by computed tomography (CT) scan of the spine. Clinical outcomes were assessed by visual analog scale (VAS) and Oswestry Disability Index (ODI). Results There was a statistically significant difference in the incidence rate of cement extravasation between vertebroplasty and kyphoplasty groups ( P < 0.04). The most common site of cement extravasation was in paravertebral soft tissues for vertebroplasty (n = 33, 40.7%) and for kyphoplasty (n = 30, 30%). In the subgroup where cement leaked into the intradiscal space, adjacent vertebral body fractures occurred in 3/26 vertebrae (11.5%) in the vertebroplasty group and in 2/18 vertebrae (11.1%) in the kyphoplasty group. Both groups showed a statistically significant decrease in both VAS ( P < 0.001) and ODI scores ( P < 0.001). There was no significantly difference in patient satisfaction between those who had cement extravasation and those who did not, in both groups. Conclusion Kyphoplasty has an advantage in terms of less risk of cement extravasation. However, this factor did not reflect on subsequent sequelae or final clinical outcomes. This study did not find a distinct correlation between intradiscal cement extravasation and increased risk of adjacent vertebral fractures.

Extravasation emergencies: state-of-the-art management and progress in clinical research.

PubMed

Pluschnig, Ursula; Haslik, Werner; Bartsch, Rupert; Mader, Robert M

2016-01-01

In cancer treatment, extravasation is defined as an inadvertent instillation or leakage of cytotoxic drugs into the perivascular space during infusion. As a dreaded complication of chemotherapy, extravasation has gained increasing attention in recent years. Classified according to their subcutaneous toxicity, three types of cytotoxins have been established: vesicants, irritants and nonvesicant drugs. Vesicant cytotoxic drugs may induce tissue damage, ulceration and tissue necrosis. Although we have established measures to manage extravasation emergencies, prevention is of paramount importance. This may be achieved within hospitals through regular training and education, which is best provided by a specialised and experienced task force including all disciplines involved in cancer therapy. Moreover, clinical and translational studies contribute to a better management of chemotherapy-induced extravasation as shown by our group in recent years. We were able to demonstrate that the evaluation of blood flow by indocyanine green angiography in the extravasation area predicts the extent of damage and the need of future surgical intervention. When a Port-a-Cath® extravasation is detected early, a subcutaneous wash-out procedure was found to be beneficial, corroborated by the analytical evaluation of the removed cytotoxic compound epirubicin. In another study, the tissue distribution of platinum was quantified at the anatomic level in cryosections of various tissues. This novel knowledge complements and supports our current efforts to handle extravasations better. On the other hand, a number of new drugs (chemotherapy, monoclonal antibodies, checkpoint inhibitors etc.) with many open issues to reliably classify their tissue toxicity still require our attention.

[Current guidelines for prevention and management of chemotherapy extravasation].

PubMed

Bahyrycz, Jan; Pityński, Kazimierz; Ludwin, Artur; Ludwin, Inga; Gawlik, Małgorzata

2012-01-01

Cytostatic drugs extravasation is the serious side effect of chemotherapy. It may lead to health-threatening complications as well as to impairment of cancer patients quality of life. Prevention, early diagnosis and appropriate treatment significantly reduce the consequences of extravasation. Training of medical staff and patients education have enormous importance on this point.

The evidence for and against different modes of tumour cell extravasation in the lung: diapedesis, capillary destruction, necroptosis, and endothelialization.

PubMed

Paku, Sándor; Laszlo, Viktoria; Dezso, Katalin; Nagy, Peter; Hoda, Mir Alireza; Klepetko, Walter; Renyi-Vamos, Ferenc; Timar, Jozsef; Reynolds, Andrew R; Dome, Balazs

2017-03-01

The development of lung metastasis is a significant negative prognostic factor for cancer patients. The extravasation phase of lung metastasis involves interactions of tumour cells with the pulmonary endothelium. These interactions may have broad biological and medical significance, with potential clinical implications ranging from the discovery of lung metastasis biomarkers to the identification of targets for intervention in preventing lung metastases. Because of the potential significance, the mechanisms of tumour cell extravasation require cautious, systematic studies. Here, we discuss the literature pertaining to the proposed mechanisms of extravasation and critically compare a recently proposed mechanism (tumour cell-induced endothelial necroptosis) with the already described extravasation mechanisms in the lung. We also provide novel data that may help to explain the underlying physiological basis for endothelialization as a mechanism of tumour cell extravasation in the lung. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Successful combined treatment with total parenteral nutrition fluid extravasation injuries in preterm infants.

PubMed

Cho, Ky Young; Lee, Soo Jung; Burm, Jin Sik; Park, Eun Ae

2007-06-01

Extravasation injuries in the neonatal intensive care unit are not rare during parenteral hyperalimentation. There have been many different methods of management. We report five premature infants with wounds of hyperalimentation fluid extravasation managed by the antibacterial ointment (Terramycin ophthalmic ointment and sesame oil and a antiinflammatory herbal mixture (MEBO).) The mean gestational age of patients was 31(+2) weeks (range, 28(+4) to 35(+6) weeks), and the mean weight at extravasation was 1,930 g (range, 1,140 to 2,680 g). Extravasation occurred within the mean of 32 days (range, 17 to 50 days). The method of dressing was application of a thick layer of this mixture covered by vaseline and wet gauze renewed at an interval of 8-12 hr after irrigating the wounds thoroughly with normal saline. The mean duration of dressing was 30 days (range, 20-50 days). The wounds had healed completely leaving a small size of contracture without functional abnormality. We conclude that this therapy may be considered for an alternative treatment and warrants clinical trials for the confirmation of the local management of extravasation injury.

Successful Combined Treatment with Total Parenteral Nutrition Fluid Extravasation Injuries in Preterm Infants

PubMed Central

Cho, Ky Young; Lee, Soo Jung; Burm, Jin Sik

2007-01-01

Extravasation injuries in the neonatal intensive care unit are not rare during parenteral hyperalimentation. There have been many different methods of management. We report five premature infants with wounds of hyperalimentation fluid extravasation managed by the antibacterial ointment (Terramycin ophthalmic ointment™) and sesame oil and a antiinflammatory herbal mixture (MEBO™). The mean gestational age of patients was 31+2 weeks (range, 28+4 to 35+6 weeks), and the mean weight at extravasation was 1,930 g (range, 1,140 to 2,680 g). Extravasation occurred within the mean of 32 days (range, 17 to 50 days). The method of dressing was application of a thick layer of this mixture covered by vaseline and wet gauze renewed at an interval of 8-12 hr after irrigating the wounds thoroughly with normal saline. The mean duration of dressing was 30 days (range, 20-50 days). The wounds had healed completely leaving a small size of contracture without functional abnormality. We conclude that this therapy may be considered for an alternative treatment and warrants clinical trials for the confirmation of the local management of extravasation injury. PMID:17596679

Negative-pressure wound therapy and early pedicle flap reconstruction of the chest wall after epirubicin extravasation.

PubMed

Papadakis, Marios; Rahmanian-Schwarz, Afshin; Bednarek, Marzena; Arafkas, Mohamed; Holschneider, Philipp; Hübner, Gunnar

2017-05-15

Accidental extravasation is a serious iatrogenic injury among patients receiving anthracycline-containing chemotherapy. The aim of this work is to present a combination therapy for chest wall reconstruction following epirubicin extravasation. Herein, we report a 68-year-old woman with massive soft tissue necrosis of the anterolateral chest wall after epirubicin extravasation from a port implanted in the subclavicular area. The necrotic tissue was resected, the port was removed, and negative-pressure wound therapy was applied. Three weeks later, a latissimus dorsi pedicle flap was successfully used to cover the defect. To the best of the authors' knowledge, this is the first report of a strategy comprising the combination of negative-pressure wound therapy and a latissimus pedicle flap for reconstruction of the chest wall after soft tissue necrosis following epirubicin extravasation.

Early surgical suction and washout for treatment of cytotoxic drug extravasations.

PubMed

Vandeweyer, E; Deraemaecker, R

2000-02-01

This case report is presented to assess safety and efficiency of early suction and saline washout of extravasated cytotoxic drugs. Through multiple small skin incisions, the area of extravasation is first suctioned and subsequently extensively washed out with saline. Incisions are left open and the arm is elevated for 24 hours. A complete healing was obtained in five days without any skin or soft tissue loss. No additional treatment was needed. Early referral and surgical treatment by suction and washout is a safe and reliable treatment protocol for major cytotoxic drug extravasation injuries.

Iatrogenic chylothorax due to pleural cavity extravasation of total parenteral nutrition in two adults receiving nutrition through a peripherally inserted central catheter.

PubMed

Johnson, Thomas J; Jamous, Fady G; Kooistra, Alma; Zawada, Edward T

2010-02-01

Extravasation of total parenteral nutrition (TPN) delivered via central lines is a known potential complication, but significant extravasations of infusate into the pleural space when using peripherally inserted central catheters (PICCs) have not been reported in adults. We report 2 cases ofpleural cavity extravasation ofTPN delivered via a PICC. Measurement of the glucose level of the effusate is a quick way to determine the presence of TPN and should be considered in any patient receiving TPN via any type of central line with a rapidly developing effusion.

Treatment of extravasation of both doxorubicin and vincristine administration in a Y-site infusion.

PubMed

Comas, D; Mateu, J

1996-03-01

To describe a patient treated with vincristine, doxorubicin, and dexamethasone who experienced extravasation of both doxorubicin and vincristine during a Y-site infusion. A 74-year-old white woman was diagnosed with multiple myeloma IgA kappa in stage IIA. One year after a complete remission she relapsed. Her treatment included daily doxorubicin 16 mg in 500 mL of dextrose 5% and vincristine 0.4 mg in 500 mL of dextrose 5% administered in a Y-site continuous infusion into a peripheral vein of her left forearm. Extravasation occurred during administration of these drugs. Immediately, chondroitinsulfatase, a mucopolysaccharidase similar to hyaluronidase, was administered subcutaneously around the extravasation area and repeated 24 hours later. Furthermore, dimethyl sulfoxide 90% v/v was applied topically on the area four times daily for 2 weeks. All inflammatory signs resolved and no necrosis developed. Ths is the first report of an extravasation of two cytotoxic drugs. Doxorubicin and vincristine have different antidotes and opposite physical treatments for their extravasation. The antidotes dimethyl sulfoxide and chondroitinsulfatase have different mechanisms of action, but both cause uptake of the cytotoxic agent from the tissue and are likely to be administered together. No warming or cooling was performed. Topical dimethyl sulfoxide four times daily for 14 days plus subcutaneous chondroitinsulfatase in one or two applications effectively treated an extravasation of both doxorubicin and vincristine in our patient.

Correlation Between Extravasation and Alterations of Cerebrovascular Laminin and β-Dystroglycan Immunoreactivity Following Cryogenic Lesions in Rats.

PubMed

Kálmán, Mihály; Tóth, László; Szöllosi, Dávid; Oszwald, Erzsébet; Mahalek, Judit; Sadeghian, Sam

2017-11-01

The blood-brain barrier becomes "leaky" following lesions. Former studies revealed that following lesions the immunoreactivity of cerebrovascular laminin becomes detectable whereas that of β-dystroglycan disappears. These alterations may be indicators of glio-vascular decoupling that may result in the impairment of the blood-brain-barrier. This study investigates correlation between the post-lesion extravasation and the above-mentioned immunohistochemical alterations. Following cryogenic lesions, the survival periods lasted 5, 10, 30 minutes, 1 or 12 hours, or 1 day. Some brains were fixed immediately post-lesion. Immunofluorescent reactions were performed in floating sections. The extravasation was detected with immunostaining for plasma fibronectin and rat immunoglobulins. When the survival period was 30 minutes or longer, the area of extravasation corresponded to the area of altered laminin and β-dystroglycan immunoreactivities. Following immediate fixation some laminin immunoreactivity was already detected. The extravasation seemed to precede this early appearance of laminin immunoreactivity. The β-dystroglycan immunoreactivity disappeared later. When the extravasation spread into the corpus callosum, vascular laminin immunoreactivity appeared but the β-dystroglycan immunoreactivity persisted. It seems that extravasation separates the glial and vascular basal laminae, which results in the appearance of laminin immunoreactivity. The disappearance of β-dystroglycan immunoreactivity is neither a condition nor an inevitable consequence of the 2 other phenomena. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Nonoperative Management of Extravasation Injuries Associated With Neonatal Parenteral Nutrition Using Multiple Punctures and a Hydrocolloid Dressing.

PubMed

Sung, Kun-Yong; Lee, Sang-Yeul

2016-05-01

Neonatal extravasation injuries are often associated with peripheral parenteral nutrition. Several treatment modalities have been developed and used for managing these injuries with variable results. However, there is a lack of consensus regarding the management of neonatal extravasation injuries. The aim of this paper is to introduce a new nonoperative method for the treatment of neonatal extravasation injuries associated with parenteral nutrition. The authors made multiple punctures on the extravasated wound using a No. 11 scalpel blade tip and applying a DuoDERM Extra Thin (ConvaTec Inc, Princeton, NJ) dressing, a hydrocolloid dressing. The dressing was changed every 6 hours on the first day, and dressing changes were continued with decreasing frequency according to the amount of exudate until the wound healed. After the devitalized tissue began to demarcate and autolyse, surgical debridement was gradually performed. Twelve neonatal extravasation injuries, which occurred between November 2010 and June 2014, were evaluated. The mean follow-up duration was 10 months. The average duration of treatment for wound healing was 25 days. All wounds healed without func- tional deficits and conspicuous scars. The authors suggest their new method of using multiple punctures and a hydrocolloid dressing is an easy, effective, and minimally invasive treatment for neonatal extravasation injuries associated with peripheral parenteral nutrition, and it can be used as an alternative treatment option.

Characterization of the effect of hyperthermia on nanoparticle extravasation from tumor vasculature.

PubMed

Kong, G; Braun, R D; Dewhirst, M W

2001-04-01

The efficacy of novel cancer therapeutics can be hampered by inefficient delivery of agents to the tumor at effective concentrations. Liposomes have been used as a method to overcome some delivery issues and, in combination with hyperthermia, have been shown to increase drug delivery to tumors. This study investigates the effects of a range of temperatures (34-42 degrees C) and hyperthermia treatment scheduling (time between hyperthermia and drug administration as well as between consecutive hyperthermia treatments) on the extravasation of nanoparticles (100-nm liposomes) from tumor microvasculature in a human tumor (SKOV-3 ovarian carcinoma) xenograft grown in athymic nude mouse window chambers. Under normothermic conditions (34 degrees C) and at 39 degrees C, nanoparticles were unable to extravasate into the tumor interstitium. From 40 to 42 degrees C, nanoparticle extravasation increased with temperature, reaching maximal extravasation at 42 degrees C. Temperatures higher than 42 degrees C led to hemorrhage and stasis in tumor vessels. Enhanced nanoparticle extravasation was observed several hours after heating, decaying back to baseline at 6 h postheating. Reheating (42 degrees C for 1 h) 8 h after an initial heating (42 degrees C for 1 h) did not result in any increased nanoparticle extravasation, indicating development of vascular thermotolerance. The results of this study have implications for the application and scheduling of hyperthermia combined with other therapeutics (e.g., liposomes, antibodies, and viral vectors) for the treatment of cancer.

Sacroplasty procedural extravasation with high viscosity bone cement: comparing the intraoperative long-axis versus short-axis techniques in osteoporotic cadavers.

PubMed

Miller, Jeffrey W; Diani, Art; Docsa, Steve; Ashton, Kristi; Sciamanna, Michele

2017-09-01

Percutaneous sacroplasty involves image-guided injection of bone cement for sacral insufficiency fractures to alleviate pain and facilitate mobility. Correct sacral placement of the cement and the risk of cement extravasation present procedural challenges. This study compares the occurrence, number, location, and surface area of high viscosity radiopaque bone cement extravasation via biplane fluoroscopy with Dyna CT between the fluoroscopically-guided intraoperative long-axis and short-axis sacroplasty techniques in osteoporotic cadavers. Ten osteoporotic cadavers underwent bilateral percutaneous instillation of VertaPlex HV High Viscosity Radiopaque Bone Cement. Long- and short-axis sacroplasty techniques were randomly assigned to zone 1 of the left or right sacral ala of each cadaver. Cement extravasation data were summarized by technique (long-axis vs short-axis) and time period (15-min and 3-hour post-procedure syngo DynaCT scan) in the form of point and CI estimates for the true proportions of cement extravasation. No procedural sacral extravasation differences were observed between the long-axis and short-axis sacroplasty techniques. There were no occurrences of intra-procedural or post-procedural cement extravasation at 15 min or 3 hours in association with either the long-axis sacroplasty technique or the short-axis sacroplasty technique. The long- and short-axis sacroplasty techniques, using high viscosity cement with careful post-procedural positioning, result in no occurrence of cement extravasation in porous osteoporotic cadaver bone. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Fluid Extravasation in Hip Arthroscopy: A Systematic Review.

PubMed

Ekhtiari, Seper; Haldane, Chloe E; de Sa, Darren; Simunovic, Nicole; Ayeni, Olufemi R

2017-04-01

The purpose of this systematic review was to (1) characterize cases of fluid extravasation during hip arthroscopy and explore common factors among them and (2) describe management strategies and outcomes of this complication. The databases MEDLINE, EMBASE, and PubMed were searched and screened in duplicate. Data regarding patient demographics, fluid management, presentation, management, and outcomes were collected. Study quality was assessed in duplicate using the Methodological Index for Non-Randomized Studies Criteria. Fourteen studies (1,286 patients) were included. Twenty-two occurrences of symptomatic fluid extravasation were reported in 21 patients (1.6% of total patients; one patient had fluid extravasation during 2 separate hip arthroscopies). Two studies of normal fluid extravasation in asymptomatic patients reported 1.13 to 3.06 L of extravasated fluid observed on computed tomography. Nine case studies were included, which provided detailed patient and surgical information. Of these 9 patients (10 cases) with a mean age of 38.2 years old (range, 15 to 55 years), 6 were female. Signs of fluid extravasation included abdominal distension (89%), hypothermia (56%), hypotension. and metabolic acidosis (33% each). Four patients required surgical intervention, while 3 underwent paracentesis. Two patients were managed conservatively. All patients stabilized and were discharged, with one patient reporting abdominal complaints at latest follow-up (length of follow-up unspecified). Fluid extravasation is a rare but potentially life-threatening complication of hip arthroscopy. It is important for surgeons and anaesthesiologists to be aware of its existence in order to recognize and manage it promptly. Most patients require interventional management by surgery or paracentesis, but some stabilize with conservative management. Level IV, systematic review of Level IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Childhood extravasation injuries: improved outcome following the introduction of hospital-wide guidelines.

PubMed

Ghanem, Ali M; Mansour, Abdulrab; Exton, Rebecca; Powell, Jonathan; Mashhadi, Syed; Bulstrode, Neil; Smith, Gillian

2015-04-01

Extravasation is an iatrogenic injury that may produce soft tissue necrosis requiring surgical reconstruction (Rose et al., 2008) and (Goon et al., 2006). Previous review of extravasation injuries within our hospital showed that early referral to plastic surgeons and washout of high-risk cases lead to favourable outcome in 86% of patients (Gault, 1993). Hospital-wide guidelines were introduced in 2005. This paper closes the audit loop by evaluating extravasation injuries outcome following the introduction of these guidelines. All patients referred to the plastic surgery department for extravasation injuries between October 2008 and October 2009 were reviewed. A favourable outcome was defined as resolution without tissue loss requiring surgical reconstruction. Patients were excluded if they sustained the extravasation in other institution. A total of 82 extravasation injuries in 78 patients were reviewed during the audit period. Mean age was 3.2 years (Median 0.2 years, Minimum 0 day, and maximum 16.7 years). The injuries were more frequent on the left half of the body (52%) and involving the upper limbs (59%). Mean time to referral was 8 h, with 60% of patients referred within 6 h of the injury, 30% in 6-12 h, and 10% referred after more than 12 h 26% of the injuries required washout treatment - the rest was treated conservatively. Tissue necrosis occurred in 3 cases (4%) but required no surgical intervention due to the small area affected. Our audit showed an improved outcome of extravasation injury following introduction of hospital-wide guidelines of early referral to specialist team and washout of high-risk cases. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Polymeric micelles and nanoemulsions as tumor-targeted drug carriers: Insight through intravital imaging.

PubMed

Rapoport, Natalya; Gupta, Roohi; Kim, Yoo-Shin; O'Neill, Brian E

2015-05-28

Intravital imaging of nanoparticle extravasation and tumor accumulation has revealed, for the first time, detailed features of carrier and drug behavior in circulation and tissue that suggest new directions for optimization of drug nanocarriers. Using intravital fluorescent microscopy, the extent of the extravasation, diffusion in the tissue, internalization by tissue cells, and uptake by the RES system were studied for polymeric micelles, nanoemulsions, and nanoemulsion-encapsulated drug. Discrimination of vascular and tissue compartments in the processes of micelle and nanodroplet extravasation and tissue accumulation was possible. A simple 1-D continuum model was suggested that allowed discriminating between various kinetic regimes of nanocarrier (or released drug) internalization in tumors of various sizes and cell density. The extravasation and tumor cell internalization occurred much faster for polymeric micelles than for nanoemulsion droplets. Fast micelle internalization resulted in the formation of a perivascular fluorescent coating around blood vessels. A new mechanism of micelle extravasation and internalization was suggested, based on the fast extravasation and internalization rates of copolymer unimers while maintaining micelle/unimer equilibrium in the circulation. The data suggested that to be therapeutically effective, nanoparticles with high internalization rate should manifest fast diffusion in the tumor tissue in order to avoid generation of concentration gradients that induce drug resistance. However an extra-fast diffusion should be avoided as it may result in the flow of extravasated nanoparticles from the tumor to normal organs, which would compromise targeting efficiency. The extravasation kinetics were different for nanodroplets and nanodroplet-encapsulated drug F-PTX suggesting a premature release of some fraction of the drug from the carrier. In conclusion, the development of an "ideal" drug carrier should involve the optimization of both drug retention and carrier diffusion parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo

PubMed Central

Broermann, Andre; Winderlich, Mark; Block, Helena; Frye, Maike; Rossaint, Jan; Zarbock, Alexander; Cagna, Giuseppe; Linnepe, Ruth; Schulte, Dörte; Nottebaum, Astrid Fee

2011-01-01

We have recently shown that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial membrane protein, associates with VE-cadherin and is required for optimal VE-cadherin function and endothelial cell contact integrity. The dissociation of VE-PTP from VE-cadherin is triggered by vascular endothelial growth factor (VEGF) and by the binding of leukocytes to endothelial cells in vitro, suggesting that this dissociation is a prerequisite for the destabilization of endothelial cell contacts. Here, we show that VE-cadherin/VE-PTP dissociation also occurs in vivo in response to LPS stimulation of the lung or systemic VEGF stimulation. To show that this dissociation is indeed necessary in vivo for leukocyte extravasation and VEGF-induced vascular permeability, we generated knock-in mice expressing the fusion proteins VE-cadherin-FK 506 binding protein and VE-PTP-FRB* under the control of the endogenous VE-cadherin promoter, thus replacing endogenous VE-cadherin. The additional domains in both fusion proteins allow the heterodimeric complex to be stabilized by a chemical compound (rapalog). We found that intravenous application of the rapalog strongly inhibited VEGF-induced (skin) and LPS-induced (lung) vascular permeability and inhibited neutrophil extravasation in the IL-1β inflamed cremaster and the LPS-inflamed lung. We conclude that the dissociation of VE-PTP from VE-cadherin is indeed required in vivo for the opening of endothelial cell contacts during induction of vascular permeability and leukocyte extravasation. PMID:22025303

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

PubMed Central

Jeon, Jessie S.; Bersini, Simone; Gilardi, Mara; Dubini, Gabriele; Charest, Joseph L.; Moretti, Matteo; Kamm, Roger D.

2015-01-01

A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine. PMID:25524628

Acute compartment syndrome of hand resulting from radiographic contrast iohexol extravasation

PubMed Central

Vinod, Kolar Vishwanath; Shravan, Rampelli; Shrivarthan, Radhakrishnan; Radhakrishna, Pedapati; Dutta, Tarun Kumar

2016-01-01

Intravenous (IV) administration of iodinated contrast agents (ICAs) is frequently employed for image enhancement while performing radiographic studies such as computed tomography and angiography. Complications related to IV administration of ICAs such as immediate hypersensitivity reactions and nephrotoxicity are well-known. However, severe skin and soft tissue injuries and acute compartment syndrome resulting from contrast extravasation are rare. This is especially so with small volume extravasation of a low osmolar, nonionic ICA such as iohexol. Here, we report a 63-year-old woman who developed acute compartment syndrome of left hand following iohexol extravasation and had swelling, blistering, cutaneous and soft tissue necrosis. She underwent fasciotomy for acute compartment syndrome of hand and later surgical debridement of necrotic skin and soft tissues was carried out. Clinical pharmacology of ICAs, extravasation injuries following their IV administration, their management and measures to reduce them are discussed in brief. PMID:27127398

Management of extravasation of oxaliplatin by mimicking its biotransformation.

PubMed

Bahadori, F; Demiray, M

2018-04-27

Although oxaliplatin (Oxali) plays a key role in the treatment of many types of cancer and has been reported to be an irritant, there is no specific and effective method for its extravasation and failure in Oxali extravasation management results in the need for plastic surgery. In the body, Oxali bio-transforms upon dilution in chloride-containing buffer salts to its di-chloro derivative and loses an oxalate molecule. Consequently, the chloride ions exchange with water molecules in the intracellular environment to produce the di-aqua derivative, which is the most active biotransformation product of Oxali in terms of forming the DNA adducts. Thus, inhibiting transformation of di-chloro to di-aqua derivatives by accumulating chloride ions at the site of extravasation and saturating the Oxali molecule with these ions is a strategy that could help manage extravasation. Injecting normal saline at this site is a simple yet effective way to achieve this goal.

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation.

PubMed

Jeon, Jessie S; Bersini, Simone; Gilardi, Mara; Dubini, Gabriele; Charest, Joseph L; Moretti, Matteo; Kamm, Roger D

2015-01-06

A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine.

Tissue necrosis following extravasation of acyclovir in an adolescent: A case report.

PubMed

Neocleous, Charalambos; Andonopoulou, Eleni; Adramerina, Alkistis; Pegkou, Antigoni; Savelieva, Olga; Georgiadou, Petroula; Drikos, Ioannis

2017-05-01

Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Acute compartment syndrome of hand resulting from radiographic contrast iohexol extravasation.

PubMed

Vinod, Kolar Vishwanath; Shravan, Rampelli; Shrivarthan, Radhakrishnan; Radhakrishna, Pedapati; Dutta, Tarun Kumar

2016-01-01

Intravenous (IV) administration of iodinated contrast agents (ICAs) is frequently employed for image enhancement while performing radiographic studies such as computed tomography and angiography. Complications related to IV administration of ICAs such as immediate hypersensitivity reactions and nephrotoxicity are well-known. However, severe skin and soft tissue injuries and acute compartment syndrome resulting from contrast extravasation are rare. This is especially so with small volume extravasation of a low osmolar, nonionic ICA such as iohexol. Here, we report a 63-year-old woman who developed acute compartment syndrome of left hand following iohexol extravasation and had swelling, blistering, cutaneous and soft tissue necrosis. She underwent fasciotomy for acute compartment syndrome of hand and later surgical debridement of necrotic skin and soft tissues was carried out. Clinical pharmacology of ICAs, extravasation injuries following their IV administration, their management and measures to reduce them are discussed in brief.

Management of anthracycline extravasation into the pleural space.

PubMed

Chang, Rachael; Murray, Nick

2016-10-01

Anthracycline extravasation is a feared complication of intravenous (i.v.) chemotherapy due to the tissue toxicity of this group of drugs. We describe a 54-year-old woman with history of stage IIIa breast cancer, receiving adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide. The chemotherapy was administered through a Poweport ® device, the position of which was confirmed with fluoroscopy and function confirmed by flushing the line. Urgent intervention was required as patient was symptomatic and experienced severe right-sided pleuritic chest pain. Radiology also confirmed the extravasation of doxorubicin into the pleural space. Surgical washout of the pleural space and 3 days therapy with i.v. dexrazoxane were carried out to prevent tissue damage and long-term sequelae. Use of dexrazoxane should always be considered following intra-pleural extravasation because of its potential efficacy and reasonable tolerability. However, the best approach to extravasation injury is prevention by systematic implementation of careful, standardized, evidence-based administration techniques.

Chemotherapy extravasations: prevention, identification, management, and documentation.

PubMed

Gonzalez, Tulia

2013-02-01

The nurses' role in safe and effective practice of chemotherapy administration is paramount. The purpose of this article is to present nurses administering chemotherapy with evidence-based information useful in eliminating or reducing the severity of an injury from a chemotherapy extravasation. Nurse education is essential to prevent, recognize, manage, and document chemotherapy extravasations. The classification of the cytotoxic drug and its mechanism of action is useful when selecting the IV access device and also will direct the nurse's intervention to manage the injury. The Oncology Nursing Society's Chemotherapy and Biotherapy Guidelines and Recommendations for Practice and the drug manufacturer are the best sources offering pharmacologic and nonpharmacologic recommendations. The nurse's best ally in the prevention, prompt recognition, and management of an extravasation is the educated patient. Documenting chemotherapy extravasation is another important step to guide the treatment plan; therefore, the document must provide complete details and the extent of the event.

Microbiota signalling through MyD88 is necessary for a systemic neutrophilic inflammatory response

PubMed Central

Karmarkar, Dipti; Rock, Kenneth L

2013-01-01

In the present study, we have found that intestinal flora strongly influence peritoneal neutrophilic inflammatory responses to diverse stimuli, including pathogen-derived particles like zymosan and sterile irritant particles like crystals. When germ-free and flora-deficient (antibiotic-treated) mice are challenged with zymosan intraperitoneally, neutrophils are markedly impaired in their ability to extravasate from blood into the peritoneum. In contrast, in these animals, neutrophils can extravasate in response to an intraperitoneal injection of the chemokine, macrophage inflammatory protein 2. Neutrophil recruitment upon inflammatory challenge requires stimulation by microbiota through a myeloid differentiation primary response gene (88) (MyD88) -dependent pathway. MyD88 signalling is crucial during the development of the immune system but depending upon the ligand it may be dispensable at the time of the actual inflammatory challenge. Furthermore, pre-treatment of flora-deficient mice with a purified MyD88-pathway agonist is sufficient to restore neutrophil migration. In summary, this study provides insight into the role of gut microbiota in influencing acute inflammation at sites outside the gastrointestinal tract. PMID:23909393

Current recommendations for prevention and therapy of extravasation reactions in dermato-oncology.

PubMed

Kähler, Katharina C; Mustroph, Dieter; Hauschild, Axel

2009-01-01

Despite the introduction of many targeted therapies, a wide variety of cytostatic agents are still frequently used in dermato-oncology. In order to avoid further morbidity in tumor patients, prevention of extravasation reactions is of highest importance. The optimal management of extravasation requires an early diagnosis, the application of specific antidotes and a well-trained oncology team.

Extravasation injuries: a review.

PubMed

Goutos, I; Cogswell, L K; Giele, H

2014-10-01

Extravasation injuries are common emergencies in clinical practice. If they are not recognized and treated promptly, they can lead to deleterious functional and cosmetic outcomes. There is a vast range of agents involved in these injuries and marked paucity of evidence to support their specific management. Following an extensive literature review, we outline management principles for clinicians involved in the care of patients with extravasation injuries. Key parameters in deciding appropriate management plans include the volume/toxicity of the agent, the necrosis interval of the injury, patient-related factors, as well as the facilities and expertise available in the setting of individual cases of extravasation. © The Author(s) 2014.

Neuropilin-2 promotes extravasation and metastasis by interacting with endothelial α5 integrin.

PubMed

Cao, Ying; Hoeppner, Luke H; Bach, Steven; E, Guangqi; Guo, Yan; Wang, Enfeng; Wu, Jianmin; Cowley, Mark J; Chang, David K; Waddell, Nicola; Grimmond, Sean M; Biankin, Andrew V; Daly, Roger J; Zhang, Xiaohui; Mukhopadhyay, Debabrata

2013-07-15

Metastasis, the leading cause of cancer death, requires tumor cell intravasation, migration through the bloodstream, arrest within capillaries, and extravasation to invade distant tissues. Few mechanistic details have been reported thus far regarding the extravasation process or re-entry of circulating tumor cells at metastatic sites. Here, we show that neuropilin-2 (NRP-2), a multifunctional nonkinase receptor for semaphorins, vascular endothelial growth factor (VEGF), and other growth factors, expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular extravasation and metastasis in zebrafish and murine xenograft models of clear cell renal cell carcinoma (RCC) and pancreatic adenocarcinoma. In tissue from patients with RCC, NRP-2 expression is positively correlated with tumor grade and is highest in metastatic tumors. In a prospectively acquired cohort of patients with pancreatic cancer, high NRP-2 expression cosegregated with poor prognosis. Through biochemical approaches as well as Atomic Force Microscopy (AFM), we describe a unique mechanism through which NRP-2 expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular adhesion and extravasation. Taken together, our studies reveal a clinically significant role of NRP-2 in cancer cell extravasation and promotion of metastasis. ©2013 AACR.

Related factors with extravasation of non-cytostatic agents in peripheral vein catheters.

PubMed

Fernández-García, Cristina; Mata-Peón, Esther; Avanzas-Fernández, Sara

To know the independent variables related to the occurrence of extravasation in patients with peripheral vein catheters (PVC). Retrospective study carried out in 6 longitudinal cuts between July 2013 an January 2014. A total of 1,442 PVC were reviewed, of which 730 met the inclusion criteria, and were divided into 2 groups: extravasation and not extravasation, with 365 cases each. The variables of age, gender, admission unit, catheter gauge, insertion site, previous insertion into the same limb, hospital unit where the insertion took place, communication difficulties, personal health history and analyzed parenterally drug administered were considered. Risk factors to develop extravasation were: female gender, with previous insertion in the same limb, <72h PVC of insertion, communication difficulties, personal health history of neoplasia and KCl, gentamicin or beta lactam treatment. Our study allows to know the variables that are related to the emergence of extravasations in patients with non-cancer treatments (gender, medical service of admission, catheter gauge, elapsed time since the insertion, patient communication difficulties, personal health history, and intravenous treatments), as well as the factors that may be considered protective. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Compartment syndrome due to extravasation of peripheral parenteral nutrition: extravasation injury of parenteral nutrition.

PubMed

Park, Huee Jin; Kim, Kyung Hoon; Lee, Hyuk Jin; Jeong, Eui Cheol; Kim, Kee Won; Suh, Dong In

2015-11-01

Compartment syndrome is a rare but devastating condition that can result in permanent neuromuscular or soft tissue injuries. Extravasation injuries, among the iatrogenic causes of compartment syndrome, occur under a wide variety of circumstances in the inpatient setting. Total parenteral nutrition via a peripheral route is an effective alternative for the management of critically ill children who do not obtain adequate nutrition via the oral route. However, there is an inherent risk of extravasation, which can cause compartment syndrome, especially when detected at a later stage. Herein, we report a rare case of compartment syndrome and skin necrosis due to extravasation, requiring emergency fasciotomy and skin graft in a 7-month-old boy who was treated with peripheral parenteral nutrition via a pressurized infusion pump. Although we cannot estimate the exact time at which extravasation occurred, the extent and degree of the wound suggest that the ischemic insult was prolonged, lasting for several hours. Pediatric clinicians and medical teams should carefully examine the site of insertion of the intravenous catheter, especially in patients receiving parenteral nutrition via a peripheral intravenous catheter with a pressurized infusion pump.

Synergistic interaction between fentanyl and the histamine H3 receptor agonist R-(alpha)-methylhistamine, on the inhibition of nociception and plasma extravasation in mice.

PubMed

Poveda, Raquel; Fernández-Dueñas, Víctor; Fernández, Alejandro; Sánchez, Sílvia; Puig, Margarita M; Planas, Eulàlia

2006-07-10

Here we report a synergistic interaction between fentanyl and the histamine H(3) receptor agonist R-(alpha)-methylhistamine on the inhibition of nociception and plasma extravasation in mice. Chronic inflammation was induced by subplantar injection of Complete Freund's Adjuvant into the right hind paw, and the effect of the drugs was evaluated 7 days later. Nociception and plasma extravasation were assessed by hot-plate and Evans blue tests respectively. Subcutaneous administration of fentanyl (0.01-0.1 mg/kg) induced dose-related anti-nociceptive and anti-extravasation effects (E(max)=100% and 62%, respectively). R-(alpha)-methylhistamine administration (0.3-3 mg/kg) showed a dose-related inhibitory effect on extravasation (E(max)=65%) but not on nociception. To analyze possible interaction between these two drugs, a dose-response curve to fentanyl plus a fixed dose of R-(alpha)-methylhistamine (0.5 mg/kg) was obtained. The dose-response curve for the combined treatment showed a shift to the left compared with that for fentanyl alone. Our results confirm that fentanyl and R-(alpha)-methylhistamine interact in a synergic way, inhibiting nociception and plasma extravasation.

NK-1 receptor desensitization and neutral endopeptidase terminate SP-induced pancreatic plasma extravasation.

PubMed

Maa, J; Grady, E F; Kim, E H; Yoshimi, S K; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-10-01

Substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin-1 receptor (NK1-R). We characterized the mechanisms regulating this response in the rat pancreas. Anesthetized rats were continuously infused with SP, and plasma extravasation was quantified using Evans blue (EB) dye. Continuous infusion of SP (8 nmol. kg(-1). h(-1)) resulted in a threshold increase in EB at 15 min, a peak effect at 30 min (150% increase), and a return to baseline by 60 min. The NK1-R antagonist CP-96,345 blocked SP-induced plasma extravasation. After 60 min, the NK1-R was desensitized to agonist challenge. Resensitization was first detected at 20 min and increased until full recovery was seen at 30 min. Inhibition of the cell-surface protease neutral endopeptidase (NEP) by phosphoramidon potentiated the effect of exogenous SP; therefore endogenous NEP attenuates SP-induced plasma extravasation. Thus the continuous infusion of SP stimulates plasma extravasation in the rat pancreas via activation of the NK1-R, and these effects are terminated by both desensitization of the NK1-R and the cell-surface protease NEP.

The effect of extracorporeal shock wave lithotripsy on the rat spinal cord.

PubMed

Karatas, A; Dosoglu, M; Zeyrek, T; Kayikci, A; Erol, A; Can, B

2008-09-01

Experimental study. To determine the effects of extracorporeal shock wave lithotripsy (ESWL) on the rat spinal cord. Animals were randomly divided into three groups. Groups 1 and 2 consisted of five rats each that underwent ESWL (2000 impulses at 15 kV and 2000 impulses at 18 kV, respectively) and group 3 contained five control rats (no shock wave treatment). ESWL-treated and control rats were compared with regard to light and electron microscopic findings of the adjacent spinal cord. Gross neurological outcomes were normal in all groups. Light microscopic examination of group 1 showed extensive extravasation of red blood cells over all the interstitial spaces. Group 2 also had haemorrhagic areas and an irregular organization of axons in the white matter. Transmission electron microscopic examination of group 1 indicated extravasated red blood cells through the endothelium and swollen axoplasm, degenerated mitochondria, destruction of myelin sheaths and a slight increase in the number of lysosomes. Extravasated red blood cells were also seen in group 2. The axoplasmic mitochondria were enlarged, but no sign of mitochondrial degeneration was observed. Lamellar degeneration of myelin sheaths and abundant lysosomes were more predominant in group 2 than in group 1. Extracorporeal shock wave lithotripsy caused not only haemorrhage but also damage to neuronal structures except the nucleus. Our findings showed that higher-energy ESWL caused more myelin degeneration in the spinal cord.

In-vivo extravasation induces the expression of interleukin 1 receptor type 1 in human neutrophils

PubMed Central

Paulsson, J M; Moshfegh, A; Dadfar, E; Held, C; Jacobson, S H; Lundahl, J

2012-01-01

In order to address neutrophil activation during inflammation we assessed the expression of interleukin 1 receptor type 1 (IL-1R1) following in-vivo extravasation. Extravasated neutrophils were collected from 11 healthy study subjects by a skin chamber technique and compared to neutrophils in peripheral blood. Expression of IL-1R1 was assessed by microarray, quantitative polymerase chain reaction (qPCR), Western blot, flow cytometry, enzyme linked immunosorbent assay (ELISA) and immunoelectron microscopy (iEM). IL-1R1 was induced following extravasation, demonstrated by both gene array and qPCR. Western blot demonstrated an increased expression of IL-1R1 in extravasated leucocytes. This was confirmed further in neutrophils by flow cytometry and iEM that also demonstrated an increased intracellular pool of IL-1R1 that could be mobilized by N-formyl-methionine-leucine-phenylalanine (fMLP). Stimulation of peripheral neutrophils with IL-1 resulted in transcription of NFκB and a number of downstream chemokines and the corresponding chemokines were also induced following in-vivo extravasation. The present results demonstrate that IL-1R1 is induced following extravasation and exists on the neutrophil surface, as well as in a mobile intracellular pool. Furthermore, neutrophils express functional IL-1R1 as demonstrated by the induction of chemokines following IL-1 stimulation. The results indicate a potential role for IL-1 in the activation of neutrophils at inflammatory sites. PMID:22385245

Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation.

PubMed

Moriuchi, H; Arai, I; Yuizono, T

1995-12-01

Activation of fibrinolysis is implicated in the development of vascular injury in certain lung injuries. It has yet to be reported that activation of plasmin is involved in extravasation caused by oleic acid (OA). We examined whether or not plasmin is involved in pulmonary extravasation by OA. Prospective trial. University laboratory. A total of 78 guinea pigs (498.9 +/- 10.6 g). Evans blue (EB) was administered to anesthetized guinea pigs. Subsequently four protocols were followed: (1) After 1 min, 60 micro l/kg of OA was injected. Perfusion was performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2) After 1 min, 15, 30 or 60 micro l/kg of OA was injected. (3) Tranexamic acid (TA) (2 g/kg) or saline was administered 30 min before OA (15 micro l/kg) injection. (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min before OA (15 micro l/kg) injection. Except in protocol 1, the chest cavity was opened 90 min after OA injection. Perfusion was then performed. Airway was separated into four parts from trachea to distal bronchus. EB was extracted from the tissues and measured. OA caused an extravasation throughout airways in a time- and dose-dependent manner. Extravasation was more conspicuous in peripheral tissues. TA significantly attenuated extravasation, while diphenhydramine hydrochloride did not. It is suggested that plasmin, but not histamine, is involved in extravasation by OA. Inhibition of plasmin can be an effective strategy for treatment of this kind of lung injury.

Quantification of cancer cell extravasation in vivo.

PubMed

Kim, Yohan; Williams, Karla C; Gavin, Carson T; Jardine, Emily; Chambers, Ann F; Leong, Hon S

2016-05-01

Cancer cell 'invasiveness' is one of the main driving forces in cancer metastasis, and assays that quantify this key attribute of cancer cells are crucial in cancer metastasis research. The research goal of many laboratories is to elucidate the signaling pathways and effectors that are responsible for cancer cell invasion, but many of these experiments rely on in vitro methods that do not specifically simulate individual steps of the metastatic cascade. Cancer cell extravasation is arguably the most important example of invasion in the metastatic cascade, whereby a single cancer cell undergoes transendothelial migration, forming invasive processes known as invadopodia to mediate translocation of the tumor cell from the vessel lumen into tissue in vivo. We have developed a rapid, reproducible and economical technique to evaluate cancer cell invasiveness by quantifying in vivo rates of cancer cell extravasation in the chorioallantoic membrane (CAM) of chicken embryos. This technique enables the investigator to perform well-powered loss-of-function studies of cancer cell extravasation within 24 h, and it can be used to identify and validate drugs with potential antimetastatic effects that specifically target cancer cell extravasation. A key advantage of this technique over similar assays is that intravascular cancer cells within the capillary bed of the CAM are clearly distinct from extravasated cells, which makes cancer cell extravasation easy to detect. An intermediate level of experience in injections of the chorioallantoic membrane of avian embryos and cell culture techniques is required to carry out the protocol.

Post chemotherapy extravasation injuries: Hypogastric flap for reconstruction of wounds over dorsum of hand.

PubMed

Salunke, Abhijeet Ashok; Nambi, G I; Sudhakar, N

2015-01-01

Management of extravasation injuries over the dorsum of hand after administration of chemotherapeutic agents. To study the results of hypogastric flap reconstruction in chemotherapy extravasation wounds over dorsum of hand. Retrospective study. At our center over 3-years period, 32 patients were treated for chemotherapy extravasation wounds. Out of these 32 patients, seven had wound over dorsum of hand. There were five males and two females, and their mean age was 45 years (range, 19 - 64 years). These patients with wound over the dorsum of hand were treated with multiple debridements and hypogastric flap reconstruction. The mean interval between extravasation wound and surgical treatment was 6.28 days (range, 4 - 10). The mean size of extravasation wound defect was 14 × 8 (range, 12 × 7 to 18 × 8). Non-dominant hand was involved in six patients and dominant hand in one patient. In four patients, the hypogastric flap was supplemented with skin graft. The hypogastric flap settled well in all patients and enabled a good wound cover. Complete division of the flap and final insetting was done under local anesthesia after 3 weeks; this was followed by limb mobilization exercises. Contour difference over the dorsum of hand was present in all the cases. The range of movement of the hand was functionally restricted in one patient. No patient in current series developed wound infection. Hypogastric flap is a reliable flap to cover wound over dorsum of hand after extravasation of chemotherapeutic agents.

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

PubMed Central

Piedimonte, G; McDonald, D M; Nadel, J A

1991-01-01

Glucocorticoids inhibit plasma extravasation induced in the rat tracheal mucosa by substance P and other tachykinins released from sensory nerves. This study was performed to determine whether this antiinflammatory effect of glucocorticoids is mediated by the tachykinin-degrading enzymes neutral endopeptidase (NEP) and kininase II (angiotensin converting enzyme, ACE). In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE. Adult male pathogen-free F344 rats were treated for 2 d with dexamethasone (0.5 mg/kg per d i.p.), or with the vehicle used to dissolve the steroid. The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 micrograms/kg) or PAF (10 micrograms/kg) was then assessed by using Monastral blue pigment as an intravascular tracer. The role of NEP and ACE activities in the changes produced by dexamethasone was investigated by examining the effect of the selective inhibitors of these enzymes, phosphoramidon and captopril. Dexamethasone reduced the substance P-induced extravasation by 57% but did not affect the PAF-induced extravasation. The suppressive effect of dexamethasone on substance P-induced extravasation was completely reversed by simultaneously inhibiting NEP and ACE activities, but the inhibition of these enzymes had no effect on PAF-induced extravasation, regardless of whether the rats were pretreated with dexamethasone or not. These results suggest that NEP and ACE mediate a selective inhibitory effect of glucocorticoids on neurogenic plasma extravasation. PMID:1711545

A Case of Traumatic Mesenteric Bleeding Controlled by only Transcatheter Arterial Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asayama, Yoshiki, E-mail: asayama@elf.coara.or.jp, E-mail: asayama@radiol.med.kyushu-u.ac.jp; Matsumoto, Shunichi; Isoda, Takuro

We report a case of mesenteric hematoma following blunt abdominal trauma that was successfully treated with transcatheter arterial embolization (TAE) and did not require surgical repair. A 43-year-old man with blunt abdominal trauma caused in a factory accident was admitted with a stable general condition and laboratory data. On CT examination, a large mesenteric hematoma with extravasation of contrast media was observed. TAE was first attempted to control the bleeding. A superior mesenteric angiogram showed extravasation of contrast medium from a branch of the ileocolic artery and obstruction of the cecal branch. After successful TAE using microcoils, the distal portionmore » of the cecal branch was still preserved via collateral circulation. No abdominal symptoms have occurred during the 7 months following TAE. In mesenteric injury cases with limited intestinal damage, TAE may therefore be a reasonable alternative to emergent laparotomy.« less

Bullous dermatosis associated with vancomycin extravasation.

PubMed

Bohm, Nicole M; Wong, Jeffrey G

2012-02-01

Cutaneous side effects related to vancomycin therapy have been reported including histamine-related reactions, linear IgA bullous dermatosis, Stevens-Johnson syndrome, maculopapular rash and drug rash with eosinophilia and systemic symptoms. In all instances, these reports were due to the systemic administration of vancomycin and subsequent immunological reactions to the medication. Drug extravasation into soft tissues can result in a variety of clinical outcomes usually related to physiochemical properties of the drug extravasated and its diluents or pharmacologic effects on the vasculature and tissue. The authors report a patient who experienced vancomycin extravasation that resulted in a localized bullous eruption resembling linear IgA bullous dermatosis, a phenomenon not previously described in the literature.

Diode Laser Assisted Excision and Low Level Laser Therapy in the Management of Mucus Extravasation Cysts: A Case Series

PubMed Central

Ahad, Abdul; Tandon, Shruti; Lamba, Arundeep Kaur; Faraz, Farrukh; Anand, Parimal; Aleem, Abdul

2017-01-01

Introduction: Mucus extravasation cyst is a commonly occurring lesion in oral cavity that may result from traumatic severance of a salivary gland duct with subsequent extravasation of mucus into fibrous connective tissue. After a conventional excision or marsupialization, recurrence is not uncommon. Diode laser offers an effective modality for management of such lesions. Case Reports: Four patients were referred with painless fluctuant swellings on labial and buccal mucosa. After recording history and clinical examination, provisional diagnosis of mucocele was made. All the lesions were excised with a diode laser and biopsy was performed. Surgical wounds were treated with low-level laser therapy (LLLT). Results: Uneventful healing was observed in all 4 cases. Significant reduction in postoperative discomfort was recorded after application of LLLT. Histopathological findings were suggestive of mucus extravasation cysts. Conclusion: Diode laser appears to be a good alternative to conventional modalities for the management of mucus extravasation cysts. PMID:29123637

Diode Laser Assisted Excision and Low Level Laser Therapy in the Management of Mucus Extravasation Cysts: A Case Series.

PubMed

Ahad, Abdul; Tandon, Shruti; Lamba, Arundeep Kaur; Faraz, Farrukh; Anand, Parimal; Aleem, Abdul

2017-01-01

Introduction: Mucus extravasation cyst is a commonly occurring lesion in oral cavity that may result from traumatic severance of a salivary gland duct with subsequent extravasation of mucus into fibrous connective tissue. After a conventional excision or marsupialization, recurrence is not uncommon. Diode laser offers an effective modality for management of such lesions. Case Reports: Four patients were referred with painless fluctuant swellings on labial and buccal mucosa. After recording history and clinical examination, provisional diagnosis of mucocele was made. All the lesions were excised with a diode laser and biopsy was performed. Surgical wounds were treated with low-level laser therapy (LLLT). Results: Uneventful healing was observed in all 4 cases. Significant reduction in postoperative discomfort was recorded after application of LLLT. Histopathological findings were suggestive of mucus extravasation cysts. Conclusion: Diode laser appears to be a good alternative to conventional modalities for the management of mucus extravasation cysts.

Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice.

PubMed

Ishida, O; Maruyama, K; Sasaki, K; Iwatsuru, M

1999-11-10

We have examined the size dependence of extravasation and interstitial localization of polyethyleneglycol-coated liposomes (PEG-liposomes) in the solid tumor tissue by means of electron microscopic observation. Liposomes composed of distearoyl phosphatidylcholine, cholesterol and distearoylphosphatidylethanolamine derivative of polyethyleneglycol (PEG) were prepared in various size ranges. PEG-liposomes with an average diameter of 100-200 nm showed the most prolonged circulation time and the greatest tumor accumulation in all the solid tumors employed in this experiment. Although large PEG-liposomes with a diameter of 400 nm showed a short circulation time in normal mice, the results in splenectomized mice indicated that they do have an intrinsic prolonged circulation character in vivo. However, large PEG-liposomes could not extravasate into solid tumor tissue. These results indicate that the size of liposomes is critical for extravasation. The electron microscopic observations revealed the almost exclusive engulfment of extravasated liposomes by tumor-associated macrophages; very few were taken up by tumor cells.

Infiltration and extravasation.

PubMed

Hadaway, Lynn

2007-08-01

The Infusion Nurses Society's national standards of practice require that a nurse who administers IV medication or fluid know its adverse effects and appropriate interventions to take before starting the infusion. A serious complication is the inadvertent administration of a solution or medication into the tissue surrounding the IV catheter--when it is a nonvesicant solution or medication, it is called infiltration; when it is a vesicant medication, it is called extravasation. Both infiltration and extravasation can have serious consequences: the patient may need surgical intervention resulting in large scars, experience limitation of function, or even require amputation. Another long-term effect is complex regional pain syndrome, a neurologic syndrome that requires long-term pain management. These outcomes can be prevented by using appropriate nursing interventions during IV catheter insertion and early recognition and intervention upon the first signs and symptoms of infiltration and extravasation. Nursing interventions include early recognition, prevention, and treatment (including the controversial use of antidotes, and heat and cold therapy). Steps to manage infiltration and extravasation are presented.

Sulfadiazine-Induced Obstructive Nephropathy Presenting with Upper Urinary Tract Extravasation.

PubMed

Kabha, Maharan; Dekalo, Snir; Barnes, Sophie; Mintz, Ishay; Matzkin, Haim; Sofer, Mario

2016-01-01

Background: Obstructive nephropathy is an uncommon side effect of sulfadiazine, which is used for the treatment of toxoplasmosis. We present a case of acute renal colic and urine extravasation of a patient shortly after she was started on this medication. Case Presentation: A 31-year-old female presented with acute renal colic 2 weeks after starting treatment with sulfadiazine and pyrimethamine for ocular toxoplasmosis. Results: A noncontrast computed tomography revealed left hydronephrosis and fluid located around the kidney and in the left gutter. There were no urinary stones. Administration of intravenous contrast revealed significant urine extravasation at the level of the ureteropelvic junction. Intravenous contrast injection confirmed that the extravasation consisted of urine leakage at the ureteropelvic junction. Her clinical condition improved with the insertion of an internal stent, which was left in place for 4 weeks. A retrograde pyelography performed at the time of the internal stent removal ruled out persistent extravasation and filling defects in the left upper urinary tract. Considering the clinical circumstances and the imaging results, it appears that this is a first reported case of sulfadiazine-induced obstructive uropathy associated with urine extravasation. Conclusion: Although rare, obstructive uropathy related to sulfadiazine medication should be promptly suspected, diagnosed, and treated. Patients should be instructed to substantially increase their liquid intake while on that medication.

Onyx extravasation during embolization of a brain arteriovenous malformation.

PubMed

Ikeda, Hiroyuki; Imamura, Hirotoshi; Agawa, Yuji; Imai, Yukihiro; Tani, Shoichi; Adachi, Hidemitsu; Ishikawa, Tatsuya; Mineharu, Yohei; Sakai, Nobuyuki

2017-04-01

During Onyx embolization to treat brain arteriovenous malformation (AVM), carefully observing the penetration of Onyx to the nidus is important in order to avoid complications such as hemorrhage, ischemia, and difficulty with microcatheter removal. We encountered a case of Onyx extravasation during embolization of a cerebellar AVM confirmed by surgical resection and pathological analysis. The patient was a 44-year-old man with Spetzler-Martin grade I cerebellar AVM who underwent Onyx embolization prior to resection of the brain AVM. While injecting Onyx into the nidus using the "plug-and-push" technique, Onyx extravasation was observed. Onyx injection was paused and subsequently restarted, thereby allowing continuation of embolization. An oblate Onyx cast that was entirely covered in cerebellar tissue was removed during total resection of the AVM, performed the same day. The surgically removed oblate Onyx cast did not contain brain tissue or vessel wall, and immunohistochemical staining against glial fibrillary acidic protein (GFAP) showed Onyx penetration into GFAP-positive cerebellar tissue. Onyx extravasation was confirmed based on intraoperative findings during resection as well as pathological findings. The patient has been followed for four years postoperatively, and adverse events caused by Onyx extravasation have not been observed. Unexpected cast of Onyx, remote from the vascular architecture of the AVM, may represent an intra-parenchymal extravasation.

Onyx extravasation during embolization of a brain arteriovenous malformation

PubMed Central

Imamura, Hirotoshi; Agawa, Yuji; Imai, Yukihiro; Tani, Shoichi; Adachi, Hidemitsu; Ishikawa, Tatsuya; Mineharu, Yohei; Sakai, Nobuyuki

2016-01-01

During Onyx embolization to treat brain arteriovenous malformation (AVM), carefully observing the penetration of Onyx to the nidus is important in order to avoid complications such as hemorrhage, ischemia, and difficulty with microcatheter removal. We encountered a case of Onyx extravasation during embolization of a cerebellar AVM confirmed by surgical resection and pathological analysis. The patient was a 44-year-old man with Spetzler-Martin grade I cerebellar AVM who underwent Onyx embolization prior to resection of the brain AVM. While injecting Onyx into the nidus using the “plug-and-push” technique, Onyx extravasation was observed. Onyx injection was paused and subsequently restarted, thereby allowing continuation of embolization. An oblate Onyx cast that was entirely covered in cerebellar tissue was removed during total resection of the AVM, performed the same day. The surgically removed oblate Onyx cast did not contain brain tissue or vessel wall, and immunohistochemical staining against glial fibrillary acidic protein (GFAP) showed Onyx penetration into GFAP-positive cerebellar tissue. Onyx extravasation was confirmed based on intraoperative findings during resection as well as pathological findings. The patient has been followed for four years postoperatively, and adverse events caused by Onyx extravasation have not been observed. Unexpected cast of Onyx, remote from the vascular architecture of the AVM, may represent an intra-parenchymal extravasation. PMID:27903925

Complement C3 and C5 play critical roles in traumatic brain cryoinjury: blocking effects on neutrophil extravasation by C5a receptor antagonist☆

PubMed Central

Sewell, Diane L.; Nacewicz, Brendon; Liu, Frances; Macvilay, Sinarack; Erdei, Anna; Lambris, John D.; Sandor, Matyas; Fabry, Zsuzsa

2016-01-01

The role of complement components in traumatic brain injury is poorly understood. Here we show that secondary damage after acute cryoinjury is significantly reduced in C3−/− or C5−/− mice or in mice treated with C5a receptor antagonist peptides. Injury sizes and neutrophil extravasation were compared. While neutrophil density increased following traumatic brain injury in wild type (C57BL/6) mice, C3-deficient mice demonstrated lower neutrophil extravasation and injury sizes in the brain. RNase protection assay indicated that C3 contributes to the induction of brain inflammatory mediators, MIF, RANTES (CCL5) and MCP-1 (CCL2). Intracranial C3 injection induced neutrophil extravasation in injured brains of C3−/− mice suggesting locally produced C3 is important in brain inflammation. We show that neutrophil extravasation is significantly reduced in both C5−/− mice and C5a receptor antagonist treated cryoinjured mice suggesting that one of the possible mechanisms of C3 effect on neutrophil extravasation is mediated via downstream complement activation products such as C5a. Our data indicates that complement inhibitors may ameliorate traumatic brain injury. PMID:15342196

Identification of highly concentrated dextrose solution (50% dextrose) extravasation and treatment--a clinical report.

PubMed

Lawson, Sarah L; Brady, William; Mahmoud, Ahmed

2013-05-01

Treatment for significant hypoglycemia includes administration of dextrose containing agents, including 50% dextrose (D50%W) intravenously. Significant extravasation of D50%W can lead to complications, including skin and soft tissue injury, loss of limb, or death. The aim of this case report, using an interdisciplinary team approach, explores extravasation protocols as well as literature review, is to provide information about the proper use of hyaluronidase in patients with D50%W extravasations. A 46-year-old African American man presented to the emergency department (ED) after blood glucose level was initially 13 mg/dL. Emergency medical service established a large bore intravenous (IV) line in the right antecubital vein and administered a total of 50 g of D50%W. Upon arrival to the ED, the patient's level of consciousness had significantly improved. After arrival to the ED, the patient started complaining of pain in his right arm, near the site of the IV line insertion. On inspection, the IV site was grossly infiltrated. Hospital protocols for hyperosmolar infiltration were used. Extravasation is a common medical complication of infused medications and needs to be properly identified and treated. The multitude of skills from nursing, medicine, and pharmacy ensures that extravasation is managed appropriately and effectively to ensure safety to patients. Recognition, communication, and awareness of the institutional guidelines on how to treat infiltration and extravasation should be encouraged in all ED and intensive care unit medical personnel who deal with a variety of infusions and IV medications that have serious implications if not treated correctly.

Taxanes: vesicants, irritants, or just irritating?

PubMed

Barbee, Meagan S; Owonikoko, Taofeek K; Harvey, R Donald

2014-01-01

Several classes of antineoplastic agents are universally referred to as vesicants with ample supporting literature. However, the literature surrounding the taxanes is controversial. While the American Society of Clinical Oncology and Oncology Nursing Society Chemotherapy Administration Safety Standards and the Chemotherapy and Biotherapy Guidelines and Recommendations for Practice identify the risks of extravasation and the parameters surrounding the infusion of known vesicants, recommend administration sites for known agents, and recommend antidotes for particular extravasation cases, they fail to provide specific recommendations for the administration of individual taxanes, or a classification system for antineoplastic agents as vesicants, irritants, or inert compounds. There is also a lack of prescribing information regarding such recommendations. The lack of a formal classification system further complicates the accurate delineation of vesicant antineoplastic agents and subsequent appropriate intravenous administration and extravasation management. There are several factors that make the classification of taxanes as vesicants or irritants challenging. Comprehensive preclinical data describing potential mechanisms of tissue damage or vesicant-like properties are lacking. Furthermore, most case reports of taxane extravasation fail to include the parameters surrounding administration, such as the concentration of medication and duration of infusion, making it difficult to set parameters for vesicant potential. Subsequently, many practitioners default to central venous administration of taxanes without evidence that such administration minimizes the risk of extravasation or improves outcomes thereof. Here, we review briefly the data surrounding taxane extravasation and potential vesicant or irritant properties, classify the taxanes, and propose a spectrum for antineoplastic agent potential to cause tissue injury that warrants clinical intervention if extravasation occurs.

Transcatheter Arterial Embolization with N-Butyl-2-Cyanoacrylate in the Management of Spontaneous Hematomas.

PubMed

Ozyer, Umut

2017-01-01

Spontaneous hematoma refractory to conservative management is a potentially serious condition that requires prompt diagnosis and intervention. The purpose of this study was to evaluate the performance of computed tomography (CT) in the treatment planning and to report the effectiveness of transcatheter embolization with N-butyl-2-cyanoacrylate (NBCA). Forty-one interventions in 38 patients within a 12-year period were evaluated. CT and angiograms were reviewed for the location of the hematoma, the presence of extravasation, and the correlation of CT and angiography findings. Arterial extravasation was present on 34/39 CT scans. Angiograms confirmed the CT scans in 29 cases. Angiograms revealed extravasation in four cases which CT showed venous bleeding (n = 2) or no bleeding (n = 2). Five patients with arterial and 1 patient with venous extravasation on CT images had no extravasation on angiograms. Embolization was performed to all arteries with extravasation on angiograms. Empiric embolization of the corresponding artery on the CT was performed when there was no extravasation on angiograms. Embolization procedures were performed with 15 % NBCA diluted with iodized oil. Technical success was achieved in 40/41 (97.6 %) interventions. Clinical success was achieved in 35 patients with a single, in 1 patient with 2, and in 1 patient with 3 interventions. No complications related to embolization procedure occurred. None of the patients died due to a progression of the hematoma. NBCA is an effective and safe embolic agent to treat hematoma refractory to conservative management. Contrast-enhanced CT may provide faster and more effective intervention. Retrospective.

Relevance of antecedent venography in percutaneous vertebroplasty for the treatment of osteoporotic compression fractures.

PubMed

Gaughen, John R; Jensen, Mary E; Schweickert, Patricia A; Kaufmann, Timothy J; Marx, William F; Kallmes, David F

2002-04-01

Controversy exists regarding the utility of antecedent venography in percutaneous vertebroplasty. Our purpose was to determine whether antecedent venography improves clinical outcomes and/or decreases extravertebral cement extravasation in these procedures. We retrospective reviewed outcomes of consecutive percutaneous vertebroplasty procedures performed at our institution to define two populations, each consisting of 24 patients treated at 42 vertebral levels. Group 1 included patients who underwent antecedent venography, and group 2 included patients treated without venography. Clinical outcomes were assessed with quantitative measurements of pain and mobility. Venograms and postprocedural radiographs were interpreted to evaluate the number of vertebrae with extravertebral cement extravasation, degree of extravasation at each level, and correlation between venography and vertebroplasty. Pain improved in 19 of 20 group 1 patients, compared with 21 of 22 group 2 patients; mean postoperative pain levels were 1.3 and 1.8, respectively (P =.50), on a scale of 0 (no pain) to 10 (worst pain). All 11 group 1 patients with impaired preoperative mobility reported postoperative improvement, as did all 12 group 2 patients; mean levels of postoperative impaired mobility for groups 1 and 2 were 0.35 and 0.27, respectively (P =.43). Twenty-two of 42 vertebrae treated in group 1 demonstrated extravasation, compared with 28 of 42 in group 2 (P =.266); amounts of extravasation did not differ. Among 22 levels of extravasation in group 1, venograms in 14 showed correlative extravasation. Antecedent venography does not significantly improve the effectiveness or safety of percutaneous vertebroplasty performed by qualified, experienced operators.

Involvement of tumour necrosis factor-α in Clostridium perfringens β-toxin-induced plasma extravasation in mice

PubMed Central

Nagahama, M; Kihara, A; Kintoh, H; Oda, M; Sakurai, J

2008-01-01

Background and purpose: Clostridium perfringens beta-toxin, an important agent of necrotic enteritis, causes plasma extravasation due to the release of a tachykinin NK1 receptor agonist in mouse skin. In this study, we investigated the role of cytokines in beta-toxin-induced plasma extravasation. Experimental approach: Male Balb/c, C3H/HeN and C3H/HeJ mice were anaesthetized with pentobarbitone and beta-toxin was injected i.d. into shaved dorsal skin. SR140333, capsaicin, chlorpromazine and pentoxifylline were given as pretreatment when required before the injection of the toxin. Cytokines in the dorsal skin were measured by ELISA. Key results: Injection (i.d.) of beta-toxin induced a dose-dependent increase in dermal TNF-α and interleukin (IL)-1β levels with a concomitant increase in plasma extravasation, but not the release of IL-6. SR140333 and capsaicin significantly inhibited the toxin-induced release of TNF-α and IL-1β. The plasma extravasation and the release of TNF-α induced by beta-toxin were significantly inhibited by chlorpromazine and pentoxifylline which inhibit the release of TNF-α. The toxin-induced plasma extravasation in mouse skin was attenuated by pretreatment with a monoclonal antibody against TNF-α, but not anti-IL-1β. Furthermore, the toxin caused an increase in plasma extravasation in both C3H/HeN (TLR4-intact) and C3H/HeJ (TLR4-deficient) mice. In C3H/HeN mice, the toxin-induced leakage was not inhibited by pretreatment with anti-TLR4/MD-2 antibody. Conclusions and implications: These observations show that beta-toxin-induced plasma extravasation in mouse skin is related to the release of TNF-α via the mechanism involving tachykinin NK1 receptors, but not via TLR4. PMID:18264118

Rate of Contrast Extravasation on CT Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage

PubMed Central

Brouwers, H. Bart; Battey, Thomas W.K.; Musial, Hayley H.; Ciura, Viesha A.; Falcone, Guido J.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Viswanathan, Anand; Anderson, Christopher D.; Greenberg, Steven M.; Pomerantz, Stuart R.; Ortiz, Claudia J.; Goldstein, Joshua N.; Gonzalez, R. Gilberto; Rosand, Jonathan; Romero, Javier M.

2015-01-01

Background and Purpose In primary intracerebral hemorrhage (ICH), the presence of contrast extravasation following CT angiography (CTA), termed the ‘spot sign’, predicts hematoma expansion and mortality. Since the biological underpinnings of the spot sign are not fully understood, we investigated whether the rate of contrast extravasation - which may reflect the rate of bleeding - predicts expansion and mortality beyond the simple presence of the spot sign. Methods Consecutive ICH patients with first-pass CTA followed by a 90-second delayed post-contrast CT (delayed CTA) were included. CTAs were reviewed for spot sign presence by two blinded readers. Spot sign volumes on first-pass and delayed CTA and ICH volumes were measured using semi-automated software. Extravasation rates were calculated and tested for association with hematoma expansion and mortality using uni- and multivariable logistic regression. Results 162 patients were included, 48 (30%) of whom had ≥1 spot sign. Median spot sign volume was 0.04mL on first-pass CTA and 0.4mL on delayed CTA. Median extravasation rate was 0.23mL/min overall, and 0.30mL/min among expanders versus 0.07mL/min in non-expanders. Extravasation rates were also significantly higher in patients who died in hospital: 0.27mL/min versus 0.04mL/min. In multivariable analysis, the extravasation rate was independently associated with in-hospital mortality (OR1.09 [95%CI 1.04–1.18], p=0.004), 90-day mortality (OR1.15 [95%CI 1.08–1.27], p=0.0004), and hematoma expansion (OR1.03 [95%CI 1.01–1.08], p=0.047). Conclusions Contrast extravasation rate, or spot sign growth, further refines the ability to predict hematoma expansion and mortality. Our results support the hypothesis that the spot sign directly measures active bleeding in acute ICH. PMID:26243220

Rate of Contrast Extravasation on Computed Tomographic Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage.

PubMed

Brouwers, H Bart; Battey, Thomas W K; Musial, Hayley H; Ciura, Viesha A; Falcone, Guido J; Ayres, Alison M; Vashkevich, Anastasia; Schwab, Kristin; Viswanathan, Anand; Anderson, Christopher D; Greenberg, Steven M; Pomerantz, Stuart R; Ortiz, Claudia J; Goldstein, Joshua N; Gonzalez, R Gilberto; Rosand, Jonathan; Romero, Javier M

2015-09-01

In primary intracerebral hemorrhage, the presence of contrast extravasation after computed tomographic angiography (CTA), termed the spot sign, predicts hematoma expansion and mortality. Because the biological underpinnings of the spot sign are not fully understood, we investigated whether the rate of contrast extravasation, which may reflect the rate of bleeding, predicts expansion and mortality beyond the simple presence of the spot sign. Consecutive intracerebral hemorrhage patients with first-pass CTA followed by a 90-second delayed postcontrast CT (delayed CTA) were included. CTAs were reviewed for spot sign presence by 2 blinded readers. Spot sign volumes on first-pass and delayed CTA and intracerebral hemorrhage volumes were measured using semiautomated software. Extravasation rates were calculated and tested for association with hematoma expansion and mortality using uni- and multivariable logistic regressions. One hundred and sixty-two patients were included, 48 (30%) of whom had ≥1 spot sign. Median spot sign volume was 0.04 mL on first-pass CTA and 0.4 mL on delayed CTA. Median extravasation rate was 0.23 mL/min overall and 0.30 mL/min among expanders versus 0.07 mL/min in nonexpanders. Extravasation rates were also significantly higher in patients who died in hospital: 0.27 mL/min versus 0.04 mL/min. In multivariable analysis, the extravasation rate was independently associated with in-hospital mortality (odds ratio, 1.09 [95% confidence interval, 1.04-1.18], P=0.004), 90-day mortality (odds ratio, 1.15 [95% confidence interval, 1.08-1.27]; P=0.0004), and hematoma expansion (odds ratio, 1.03 [95% confidence interval, 1.01-1.08]; P=0.047). Contrast extravasation rate, or spot sign growth, further refines the ability to predict hematoma expansion and mortality. Our results support the hypothesis that the spot sign directly measures active bleeding in acute intracerebral hemorrhage. © 2015 American Heart Association, Inc.

Role of Hydrogen Sulfide in Early Blood-Brain Barrier Disruption following Transient Focal Cerebral Ischemia

PubMed Central

Jiang, Zheng; Li, Chun; Manuel, Morganne L.; Yuan, Shuai; Kevil, Christopher G.; McCarter, Kimberly D.; Lu, Wei; Sun, Hong

2015-01-01

We determined the role of endogenous hydrogen sulfide (H₂S) in cerebral vasodilation/hyperemia and early BBB disruption following ischemic stroke. A cranial window was prepared over the left frontal, parietal and temporal cortex in mice. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA) for two hours. Regional vascular response and cerebral blood flow (CBF) during ischemia and reperfusion were measured in real time. Early BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. Topical treatment with DL-propargylglycine (PAG, an inhibitor for cystathionine γ-lyase (CSE)) and aspartate (ASP, inhibitor for cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST)), but not O-(Carboxymethyl)hydroxylamine hemihydrochloride (CHH, an inhibitor for cystathionine β-synthase (CBS)), abolished postischemic cerebral vasodilation/hyperemia and prevented EB and Na-F extravasation. CSE knockout (CSE-/-) reduced postischemic cerebral vasodilation/hyperemia but only inhibited Na-F extravasation. An upregulated CBS was found in cerebral cortex of CSE-/- mice. Topical treatment with CHH didn’t further alter postischemic cerebral vasodilation/hyperemia, but prevented EB extravasation in CSE-/- mice. In addition, L-cysteine-induced hydrogen sulfide (H2S) production similarly increased in ischemic side cerebral cortex of control and CSE-/- mice. Our findings suggest that endogenous production of H2S by CSE and CAT/3-MST during reperfusion may be involved in postischemic cerebral vasodilation/hyperemia and play an important role in early BBB disruption following transient focal cerebral ischemia. PMID:25695633

The control of microvascular permeability and blood pressure by neutral endopeptidase.

PubMed

Lu, B; Figini, M; Emanueli, C; Geppetti, P; Grady, E F; Gerard, N P; Ansell, J; Payan, D G; Gerard, C; Bunnett, N

1997-08-01

Plasma extravasation from postcapillary venules is one of the earliest steps of inflammation. Substance P (SP) and bradykinin (BK) mediate extravasation and cause hypotension. The cell-surface enzyme neutral endopeptidase (NEP) inactivates both peptides. Thus, absence of NEP may predispose development of inflammation and hypotension. We examined these possibilities in mice in which the NEP gene was deleted by homologous recombination. There was widespread basal plasma extravasation in postcapillary venular endothelia in NEP-/- mice, which was reversed by recombinant NEP and antagonists of SP (NK1) and BK (B2) receptors. Mean arterial blood pressure was 20% lower in NEP-/- animals, but this was unaffected by reintroduction of recombinant NEP and the kinin receptor antagonists. The hypotension was also independent of nitric oxide (NO), because NEP-/- mice treated with a NO synthase inhibitor remained hypotensive relative to the wild type. Thus, NEP has important roles in regulating basal microvascular permeability by degrading SP and BK, and may regulate blood pressure set point through a mechanism that is independent of SP, BK and NO. The use of NEP antagonists as candidate drugs in cardiovascular disease is suggested by the blood pressure data reported herein.

Breast necrosis secondary to vasopressor extravasation: management using indocyanine green angiography and omental flap closure.

PubMed

Hagopian, Thomas M; Ghareeb, Paul A; Arslanian, Brian H; Moosavi, Benjamin L; Carlson, Grant W

2015-01-01

Extravasation is a rare but serious complication of vasopressor administration. A 60-year-old female who underwent ascending and hemiarch repair of the aorta along with aortic valve replacement developed extensive right breast and chest wall necrosis after vasopressor extravasation from an internal jugular vein central line. The patient underwent a total mastectomy due to deep tissue necrosis detected by laser-assisted indocyanine green dye angiography, and eventually required omental flap reconstruction to obtain adequate sternal coverage. This case represents a previously unreported complication of internal jugular central line extravasation of vasopressors with resultant breast and chest wall necrosis, and highlights the utility of the omentum in chest wall reconstruction. © 2015 Wiley Periodicals, Inc.

The use of dexrazoxane for the prevention of anthracycline extravasation injury.

PubMed

Hasinoff, Brian B

2008-02-01

The use of the anthracycline anticancer drugs doxorubicin, daunorubicin, epirubicin and idarubicin sometimes results in accidental extravasation injury and can be a serious complication of their use. The object of this review was to evaluate the preclinical and clinical literature on the use of dexrazoxane in preventing anthracycline-induced extravasation injury. A review of the literature was carried out using PubMed. Dexrazoxane, which is clinically used to reduce doxorubicin-induced cardiotoxicity, has been shown in two clinical studies and in several case reports to be highly efficacious in preventing anthracycline-induced extravasation injury. Dexrazoxane is a prodrug analog of the metal chelator EDTA that likely acts by removing iron from the iron-anthracycline complex, thus preventing formation of damaging reactive oxygen species.

Dexrazoxane use in the prevention of anthracycline extravasation injury.

PubMed

Hasinoff, Brian B

2006-02-01

Accidental extravasation injury from the use of the anthracycline anticancer drugs doxorubicin, daunorubicin, epirubicin and idarubicin can be a serious complication of their use. As yet, there is little consensus on the way that anthracycline extravasation injury should be clinically managed. Dexrazoxane, which is currently clinically used to reduce doxorubicin-induced cardiotoxicity, has also been shown in preclinical studies to be highly efficacious in preventing anthracycline-induced extravasation injury. Several clinical case reports of dexrazoxane for this use have also indicated positive outcomes. There are currently two multicenter Phase II/III clinical trials underway. Dexrazoxane is a prodrug analog of the metal chelator EDTA that most likely acts by removing iron from the iron-doxorubicin complex, thus preventing formation of damaging reactive oxygen species.

CT Appearance of Traumatic Inferior Vena Cava Injury.

PubMed

Tsai, Richard; Raptis, Constantine; Schuerer, Douglas J; Mellnick, Vincent M

2016-07-19

CT plays a crucial role in the evaluation of stable patients with blunt and penetrating trauma in the emergency department. Among the more severe injuries that may occur in penetrating and blunt trauma are those to the inferior vena cava (IVC). The purpose of this study was to evaluate and differentiate the CT findings associated with penetrating versus blunt trauma to the IVC to aid the radiologist in diagnosing IVC injuries. Cases of blunt and penetrating IVC injury were retrospectively identified using search queries. Criteria for inclusion were preoperative contrast-enhanced CT and surgically confirmed caval injury or direct findings of caval injury on CT with patient death before surgical confirmation could be obtained. Twelve cases of traumatic IVC injury were identified over a 9-year period: six blunt and six penetrating. The most common finding was a retroperitoneal hematoma, seen in 75% of cases. Eighty-three percent of blunt injuries were associated with hepatic lacerations and contrast material extravasation. Thirty-three percent of penetrating IVC injuries were associated with extravasation. Contour abnormalities were seen in 50% of blunt and 17% of penetrating injuries to the IVC. All three cases of IVC injury resulting in mortality occurred in the retrohepatic segment. Injury to the IVC is frequently fatal in patients with penetrating or blunt trauma. The CT appearance of IVC injury is dichotomous between the two causes, with blunt IVC injury more likely to show extravasation, contour abnormality, and associated hepatic laceration. Injury of the retrohepatic IVC portends a poor outcome. With the continued use of CT for evaluation of trauma patients, the radiologist should be familiar with IVC injury and its different CT appearances.

Transcatheter Arterial Embolization with N-Butyl-2-Cyanoacrylate in the Management of Spontaneous Hematomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozyer, Umut, E-mail: umutozyer@gmail.com

IntroductionSpontaneous hematoma refractory to conservative management is a potentially serious condition that requires prompt diagnosis and intervention. The purpose of this study was to evaluate the performance of computed tomography (CT) in the treatment planning and to report the effectiveness of transcatheter embolization with N-butyl-2-cyanoacrylate (NBCA).Materials and MethodsForty-one interventions in 38 patients within a 12-year period were evaluated. CT and angiograms were reviewed for the location of the hematoma, the presence of extravasation, and the correlation of CT and angiography findings.ResultsArterial extravasation was present on 34/39 CT scans. Angiograms confirmed the CT scans in 29 cases. Angiograms revealed extravasation inmore » four cases which CT showed venous bleeding (n = 2) or no bleeding (n = 2). Five patients with arterial and 1 patient with venous extravasation on CT images had no extravasation on angiograms. Embolization was performed to all arteries with extravasation on angiograms. Empiric embolization of the corresponding artery on the CT was performed when there was no extravasation on angiograms. Embolization procedures were performed with 15 % NBCA diluted with iodized oil. Technical success was achieved in 40/41 (97.6 %) interventions. Clinical success was achieved in 35 patients with a single, in 1 patient with 2, and in 1 patient with 3 interventions. No complications related to embolization procedure occurred. None of the patients died due to a progression of the hematoma.ConclusionNBCA is an effective and safe embolic agent to treat hematoma refractory to conservative management. Contrast-enhanced CT may provide faster and more effective intervention.Level of Evidence IIIRetrospective.« less

Real-time imaging and kinetics measurements of focused ultrasound-induced extravasation in skeletal muscle using SPECT/CT.

PubMed

Sanches, Pedro Gomes; Rossin, Raffaella; Böhmer, Marcel; Tiemann, Klaus; Grüll, Holger

2013-06-28

Drugs need to overcome several biological barriers such as the endothelium and cellular membranes in order to reach their target. Promising new therapeutics, many of which are charged and macromolecular, are not able to passively extravasate, let alone cross cell membranes, and stay mainly in the blood pool upon intravenous injection until clearance. Using focused ultrasound (fUS) in combination with circulating microbubbles (MBs) leads to temporary localized tissue permeabilization allowing extravasation of (macro) molecules from the vascular system. Thus, fUS is a promising approach for localized drug delivery. However, little is known about the permeabilization kinetics in skeletal muscle. In this study, we used single photon emission computed tomography (SPECT) to characterize the kinetics of extravasation of ¹¹¹In-labeled bovine serum albumin (BSA), a model macromolecular drug, in muscle treated with fUS and MBs. The same fUS protocol was applied to 6 groups of mice with different times, ∆t, between fUS application and BSA injection (∆t=-10, 2.5, 10, 30, 60, 90 min) followed by SPECT imaging. For ∆t ≤30min we observed an exponential accumulation of activity in an area of the treated muscle which extended to a volume larger than the fUS pattern with highest accumulation for short waiting times ∆t. The extent of extravasation decreased exponentially with increasing ∆t, with a calculated half-life of ca. 21 min, defining the time window of extravasation. The same treatment without MBs did not induce extravasation of BSA thus supporting MBs and drug co-injection strategies. These results provide essential information for the development of fUS based strategies for localized drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

An in vivo, MRI-integrated real-time model of active contrast extravasation in acute intracerebral hemorrhage.

PubMed

Aviv, R I; Huynh, T; Huang, Y; Ramsay, D; Van Slyke, P; Dumont, D; Asmah, P; Alkins, R; Liu, R; Hynynen, K

2014-09-01

The "spot sign" or contrast extravasation is strongly associated with hematoma formation and growth. An animal model of contrast extravasation is important to test existing and novel therapeutic interventions to inform present and future clinical studies. The purpose of this study was to create an animal model of contrast extravasation in acute intracerebral hemorrhage. Twenty-eight hemispheres of Yorkshire male swine were insonated with an MR imaging-guided focused sonography system following lipid microsphere infusion and mean arterial pressure elevation. The rate of contrast leakage was quantified by using dynamic contrast-enhanced MR imaging and was classified as contrast extravasation or postcontrast leakage by using postcontrast T1. Hematoma volume was measured on gradient recalled-echo MR imaging performed 2 hours postprocedure. Following this procedure, sacrificed brain was subjected to histopathologic examination. Power level, burst length, and blood pressure elevation were correlated with leakage rate, hematoma size, and vessel abnormality extent. Median (intracerebral hemorrhage) contrast extravasation leakage was higher than postcontrast leakage (11.3; 6.3-23.2 versus 2.4; 1.1-3.1 mL/min/100 g; P<.001). Increasing burst length, gradient recalled-echo hematoma (ρ=0.54; 95% CI, 0.2-0.8; P=.007), and permeability were correlated (ρ=0.55; 95% CI, 0.1-0.8; P=.02). Median permeability (P=.02), gradient recalled-echo hematoma (P=.02), and dynamic contrast-enhanced volumes (P=.02) were greater at 1000 ms than at 10 ms. Within each burst-length subgroup, incremental contrast leakage was seen with mean arterial pressure elevation (ρ=0.2-0.8). We describe a novel MR imaging-integrated real-time swine intracerebral hemorrhage model of acute hematoma growth and contrast extravasation. © 2014 by American Journal of Neuroradiology.

Extravasation of radiopharmaceuticals - a study of its frequency and estimation of absorbed doses in diagnosis and therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strand, S.E.; Grafstroem, G.; Kontestabile, E.

In all injection procedures exists a risk for extravasation. For radiopharmaceuticals, the absorbed dose at the injection site can be high because of high activity concentrations. In radionuclide therapy (RNT), this can cause deterministic effects such as tissue necrosis. To estimate the risk for extravasation, we studied various injection techniques at two nuclear medicine clinics. The frequency and magnitude of extravasations was studied in randomly selected patients. Clinic A used peripheral venous cathethers (PVC), and clinic B used direct injections with injection needles (IN). At clinic A 203 patients were investigated and at clinic B 90. All of these patientsmore » were injected with either 99mTc-DTPA, 99mTc-MAA, 99mTc-MDP or pertechnetate. Both arms were imaged with a scintillation camera as soon as possible after the injection. In the case of an extravasation, the retention time at the injection site was determined with multiple imaging, together with volume estimates. The results for PVC injected patients showed one complete extravasation. We also found that in 8% of these patients the remaining activity at the injection site was up to 2%. For the IN injected patients there was none with complete extravasation. However, in 33% of these patients the remaining activity was up to 18%. The locally absorbed doses in these diagnostically investigated patients were estimated with the MIRD formalism to be up to 0.1 Sv (10 rem). Transforming these results to the RNT, the absorbed doses can be up to 1000 times higher. In addition to the calculated absorbed doses, radionuclides localizing to the cell nucleus could enhance the effects.« less

The role of bradykinin receptor type 2 in spontaneous extravasation in mice skin: implications for non-allergic angio-oedema.

PubMed

Bisha, Marion; Dao, Vu Thao-Vi; Gholamreza-Fahimi, Ehsan; Vogt, Michael; van Zandvoort, Marc; Weber, Sarah; Bas, Murat; Khosravani, Farbod; Kojda, Georg; Suvorava, Tatsiana

2018-05-01

Non-allergic angio-oedema is a life-threatening disease mediated by activation of bradykinin type 2 receptors (B 2 receptors). The aim of this study was to investigate whether activation of B 2 receptors by endogenous bradykinin contributes to physiological extravasation. This may shed new light on the assumption that treatment with an angiotensin converting enzyme inhibitor (ACEi) results in an alteration in the vascular barrier function predisposing to non-allergic angio-oedema. We generated a new transgenic mouse model characterized by endothelium-specific overexpression of the B 2 receptor (B2 tg ) and established a non-invasive two-photon laser microscopy approach to measure the kinetics of spontaneous extravasation in vivo. The B2 tg mice showed normal morphology and litter size as compared with their transgene-negative littermates (B2 n ). Overexpression of B 2 receptors was functional in conductance vessels and resistance vessels as evidenced by B 2 receptor-mediated aortic dilation to bradykinin in presence of non-specific COX inhibitor diclofenac and by significant hypotension in B2 tg respectively. Measurement of dermal extravasation by Miles assay showed that bradykinin induced extravasation was significantly increased in B2 tg as compared with B2 n . However, neither endothelial overexpression of B 2 receptors nor treatment with the ACEi moexipril or B 2 antagonist icatibant had any effect on spontaneous extravasation measured by two-photon laser microscopy. Activation of B 2 receptors does not appear to be involved in spontaneous extravasation. Therefore, the assumption that treatment with an ACEi results in an alteration in the physiological vascular barrier function predisposing to non-allergic angio-oedema is not supported by our findings. © 2018 The British Pharmacological Society.

Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice

PubMed Central

Grady, Eileen F; Yoshimi, Shandra K; Maa, John; Valeroso, Dahlia; Vartanian, Robert K; Rahim, Shamila; Kim, Edward H; Gerard, Craig; Gerard, Norma; Bunnett, Nigel W; Kirkwood, Kimberly S

2000-01-01

Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin-1 receptor (NK1-R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis.Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1-R agonists/antagonists in rats and NK1-R(+/+)/(−/−) mice. The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized.In rats, both SP and the NK1-R selective agonist [Sar9 Met(O2)11]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1-R antagonist CP 96,345. Selective agonists of the NK-2 or NK-3 receptors had no effect.In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1-R antagonist CP 96,345.In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1-R knockout mice.In NK1-R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals.Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis. PMID:10821777

Implications of iodinated contrast media extravasation in the emergency department.

PubMed

Sonis, Jonathan D; Gottumukkala, Ravi V; Glover, McKinley; Yun, Brian J; White, Benjamin A; Kalra, Mannudeep K; Otrakji, Alexi; Raja, Ali S; Prabhakar, Anand M

2018-02-01

To characterize the management, outcomes, and emergency department (ED) length of stay (LOS) following iodinated contrast media extravasation events in the ED. All ED patients who developed iodinated contrast media extravasation following contrast-enhanced CT (CECT) from October 2007-December 2016 were retrospectively identified. Medical records were reviewed and management, complications, frequency of surgical consultation, and ED LOS were quantified using descriptive statistics. The Wilcoxon rank sum test was used to compare ED LOS in patients who did and did not receive surgical consultation. A total of 199 contrast extravasation episodes occurred in ED patients during the 9-year study period. Of these, 42 patients underwent surgical consultation to evaluate the contrast extravasation event. No patient developed progressive symptoms, compartment syndrome, or tissue necrosis, and none received treatment beyond supportive care (warm/cold packs, elevation, compression). Median ED LOS for patients who did and did not receive surgical consultation was 11.3h versus 9.0h, respectively (p<0.01). Close observation and supportive care are sufficient for contrast extravasation events in the ED without concerning symptoms (progressive pain/swelling, altered tissue perfusion, sensory changes, or blistering/ulceration). Routine surgical consultation is likely unnecessary in the absence of these symptoms - concordant with the current American College of Radiology guidelines - and may be associated with longer ED LOS without impacting management. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of Active Extravasation and Complications after Conventional Angiography for Acute Intraabdominal Bleeding.

PubMed

Haber, Zachary M; Charles, Hearns W; Erinjeri, Joseph P; Deipolyi, Amy R

2017-04-18

Conventional angiography is used to evaluate and treat possible sources of intraabdominal bleeding, though it may cause complications such as contrast-induced nephropathy (CIN). The study's purpose was to identify factors predicting active extravasation and complications during angiography for acute intraabdominal bleeding. All conventional angiograms for acute bleeding (January 2013-June 2015) were reviewed retrospectively, including 75 angiograms for intraabdominal bleeding in 70 patients. Demographics, comorbidities, vital signs, complications within one month, and change in hematocrit (ΔHct) and fluids and blood products administered over the 24 h prior to angiography were recorded. Of 75 exams, 20 (27%) demonstrated extravasation. ΔHct was the only independent predictor of extravasation ( p = 0.017), with larger ΔHct (-17%) in patients with versus those without extravasation (-1%) ( p = 0.01). CIN was the most common complication, occurring in 10 of 66 angiograms (15%). Glomerular filtration rate (GFR) was the only independent predictor ( p = 0.03); 67% of patients with GFR < 30, 29% of patients with GFR 30-60, and 8% of patients with GFR > 60 developed CIN. For patients with intraabdominal bleeding, greater ΔHct decrease over 24 h before angiography predicts active extravasation. Pre-existing renal impairment predicts CIN. Patients with large hematocrit declines should be triaged for rapid angiography, though benefits can be weighed with the risk of renal impairment.

Predictors of Active Extravasation and Complications after Conventional Angiography for Acute Intraabdominal Bleeding

PubMed Central

Haber, Zachary M.; Charles, Hearns W.; Erinjeri, Joseph P.; Deipolyi, Amy R.

2017-01-01

Conventional angiography is used to evaluate and treat possible sources of intraabdominal bleeding, though it may cause complications such as contrast-induced nephropathy (CIN). The study’s purpose was to identify factors predicting active extravasation and complications during angiography for acute intraabdominal bleeding. All conventional angiograms for acute bleeding (January 2013–June 2015) were reviewed retrospectively, including 75 angiograms for intraabdominal bleeding in 70 patients. Demographics, comorbidities, vital signs, complications within one month, and change in hematocrit (ΔHct) and fluids and blood products administered over the 24 h prior to angiography were recorded. Of 75 exams, 20 (27%) demonstrated extravasation. ΔHct was the only independent predictor of extravasation (p = 0.017), with larger ΔHct (−17%) in patients with versus those without extravasation (–1%) (p = 0.01). CIN was the most common complication, occurring in 10 of 66 angiograms (15%). Glomerular filtration rate (GFR) was the only independent predictor (p = 0.03); 67% of patients with GFR < 30, 29% of patients with GFR 30–60, and 8% of patients with GFR > 60 developed CIN. For patients with intraabdominal bleeding, greater ΔHct decrease over 24 h before angiography predicts active extravasation. Pre-existing renal impairment predicts CIN. Patients with large hematocrit declines should be triaged for rapid angiography, though benefits can be weighed with the risk of renal impairment. PMID:28420210

Evaluation of urinary extravasation and results after continence-preserving radical retropubic prostatectomy.

PubMed

Varkarakis, John; Wirtenberger, Walter; Pinggera, Germar-Michael; Berger, Andreas; Harabayashi, Toru; Bartsch, Georg; Horninger, Wolfgang

2004-11-01

To evaluate the feasibility of urinary catheter removal 10 days after a radical retropubic prostatectomy (RRP) by assessing the incidence of urinary extravasation and its effect on postoperative stricture and continence rates. During a 4.5-year period, 619 patients undergoing RRP were evaluated. If no extravasation was detected on gravity cystography, the urinary catheter was removed 10 days after RRP. In patients with significant extravasation the catheter was left in place for 3 weeks. Overall stricture and continence rates were recorded in patients at 3, 6 and 12 months after surgery. There was extravasation during cystography in 29 patients (4.6%). At 3, 6 and 12 months, continence rates after catheter removal at 10 days were 74.9%, 87.9%, and 93.6%, respectively, while in the late-removal group they were 72.4%, 84.6% and 90.9%, respectively, with no significant difference between the groups. At 3 months the overall continence rate was 74.8% and at 12 months up to 93.5%. There was no difference in stricture rates between the groups, with an overall stricture rate of 0.7%. Catheter removal 10 days after RRP is feasible, giving excellent early and late continence rates, with low anastomotic stricture rates obtained using good surgical technique. Extravasation at 10 days was rare and with proper management did not influence the final results.

[Extravasation of radiopharmaceuticals: preventive measures and management recommended by SoFRa (Société Française de Radiopharmacie)].

PubMed

Barré, E; Nguyen, M-L; Bruel, D; Fournel, C; Hosten, B; Lao, S; Vercellino, L; Rizzo-Padoin, N

2013-07-01

Radiopharmaceuticals extravasation is rare but may have serious clinical issues. Because no specific recommendations are being proposed to date, the goals of our working group created within the French Society of Radiopharmacy are to determine preventive measures and to establish a pragmatic management of extravasation of these drugs. Our preventive measures are to recognize the symptoms (erythema, venous discoloration, swelling), to know the risk factors (which are related to radiopharmaceutical, patient, site of injection, injection technique) and severity (from erythema to skin necrosis, depending on the radionuclide) and how to avoid them (training and awareness of staff, choice of injection site, route of drug administration test, use of a catheter for administration of therapeutic radiopharmaceuticals). Management should be immediate. It can be facilitated by a specific emergency kit. General measures recommended are the immediate cessation of injection, aspiration of fluid extravasation, delimitation of the extravasated area with an indelible pen, informing the doctor. Specific measures taking into account the radiotoxicity of the radionuclide and the type of radiopharmaceutical were also established. The patient should be informed by the doctor about the risks and how to take care of. Traceability of the incident must be ensured. A multidisciplinary reflexion is essential to manage the extravasation as early and effectively as possible. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Angiopellosis as an Alternative Mechanism of Cell Extravasation.

PubMed

Allen, Tyler A; Gracieux, David; Talib, Maliha; Tokarz, Debra A; Hensley, M Taylor; Cores, Jhon; Vandergriff, Adam; Tang, Junnan; de Andrade, James B M; Dinh, Phuong-Uyen; Yoder, Jeffrey A; Cheng, Ke

2017-01-01

Stem cells possess the ability to home in and travel to damaged tissue when injected intravenously. For the cells to exert their therapeutic effect, they must cross the blood vessel wall and enter the surrounding tissues. The mechanism of extravasation injected stem cells employ for exit has yet to be characterized. Using intravital microscopy and a transgenic zebrafish line Tg(fli1a:egpf) with GFP-expressing vasculature, we documented the detailed extravasation processes in vivo for injected stem cells in comparison to white blood cells (WBCs). While WBCs left the blood vessels by the standard diapedesis process, injected cardiac and mesenchymal stem cells underwent a distinct method of extravasation that was markedly different from diapedesis. Here, the vascular wall undergoes an extensive remodeling to allow the cell to exit the lumen, while the injected cell remains distinctively passive in activity. We termed this process Angio-pello-sis, which represents an alternative mechanism of cell extravasation to the prevailing theory of diapedesis. Stem Cells 2017;35:170-180 Video Highlight: https://youtu.be/i5EI-ZvhBps. © 2016 AlphaMed Press.

Prehospital Dextrose Extravasation Causing Forearm Compartment Syndrome: A Case Report.

PubMed

Chinn, Matthew; Colella, M Riccardo

2017-01-01

A 57-year-old woman was found at home by paramedics to be hypoglycemic with altered mental status. She had multiple attempts at IV access and eventually a 22G IV was established and D50 was infused into her right forearm. Extravasation of the dextrose was noted after approximately 12 g of the medication was infused. She was given a dose of glucagon intramuscularly and her mental status improved. Shortly after her arrival to the emergency department, she was noted to have findings of compartment syndrome of her forearm at the site of the dextrose extravasation. She was evaluated by plastic surgery and taken to the operating room for emergent fasciotomy. She recovered well from the operation. D50 is well known to cause phlebitis and local skin necrosis as a complication. This case illustrates the danger of compartment syndrome after D50 extravasation. It is the first documented case of prehospital dextrose extravasation leading to compartment syndrome. There may be safer alternatives to D50 administration and providers must be acutely aware to monitor for D50 infusion complications.

[Interest and feasibility of local anesthesia in the management of massive extravasation of contrast medium].

PubMed

Ho Quoc, C; Chaput, B; Grolleau, J-L

2013-04-01

Radiographic contrast medium extravasation in the upper extremity is not rare. It can be responsible for functional (compartment syndrome) and cosmetic sequelae. It is very difficult to predict the degree of final tissue injury in emergency. Currently, there is no consensus of emergency treatment. However, liposuction and saline washout as described by Gault is the usual treatment. We report the case of 42 year-old woman with radiographic contrast medium extravasation in the arm (120 cm(3)) with neurologic complications involving median nerve and medial cutaneous nerves of arm and forearm. Emergency conservative surgical washout with saline solution was performed under local anaesthesia. Drainage was realised by lipoaspiration cannula and arm massages. Clinical and radiological results were estimated. Ultimately, the patient has retained no sequela. Contrast medium extravasation in the arm with tissue complications is exceptional. We think that saline washout and lipoaspiration cannula drainage are an emergency useful treatment for radiographic contrast medium extravasation with tissue complications. Tolerance of the management was quite good. Postoperative X-rays are useful to assess treatment efficacy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Vital microscopic analysis of polymeric micelle extravasation from tumor vessels: macromolecular delivery according to tumor vascular growth stage.

PubMed

Hori, Katsuyoshi; Nishihara, Masamichi; Yokoyama, Masayuki

2010-01-01

Particles larger than a specific size have been thought to extravasate from tumor vessels but not from normal vessels. Therefore, various nanoparticles incorporating anticancer drugs have been developed to realize selective drug delivery to solid tumors. However, it is not yet clear whether nanoparticles extravasate readily from all tumor vessels including vessels of microtumors. To answer this question, we synthesized new polymeric micelles labeled with fluorescein isothiocyanate (FITC) and injected them into the tail vein of rats with implanted skinfold transparent chambers. We also analyzed, by means of time-lapse vital microscopy with image analysis, extravasation of FITC micelles from tumor vessels at different stages of growth of Yoshida ascites sarcoma LY80. Polymeric micelles readily leaked from vessels at the interface between normal and tumor tissues and those at the interface between tumor tissues and necrotic areas. The micelles showed negligible extravasation, however, from the vascular network of microtumors less than 1 mm in diameter and did not accumulate in the microtumor. Our results suggest that we must develop a novel therapeutic strategy that can deliver sufficient nanomedicine to microtumors.

Neonatal extravasation injury: prevention and management in Australia and New Zealand-a survey of current practice.

PubMed

Restieaux, Matthew; Maw, Andrew; Broadbent, Roland; Jackson, Pam; Barker, David; Wheeler, Ben

2013-03-11

Extravasation injury remains an important cause of iatrogenic injury in neonatal intensive care. This study aims to describe the current approach to extravasation injury (EI) prevention and management in Neonatal Intensive Care Units (NICUs) in Australia and New Zealand. A literature review regarding extravasation injury in the newborn was carried out to inform questionnaire design. An internet-based survey was then conducted with the clinical directors of the 27 tertiary NICUs in Australia and New Zealand. The survey received a 96% response rate. Approximately two thirds of Australian and New Zealand NICUs have written protocols for prevention and management of extravasation injury. Considerable practice variation was seen for both prevention and treatment of EI. 92% of units had experienced cases of significant EI. Australian and New Zealand tertiary neonatal units clearly recognise EI as an important cause of iatrogenic morbidity and mortality. Significant variation still exists among units with regards to guidelines for both prevention and management of EI. We recommend that neonatal staff should remain vigilant, ensuring that guidelines for the prevention and treatment of EI are available, and rigorously followed.

Pulmonary actions of the neurokinin1-specific agonist [Sar9,Met(O2)11]-substance P.

PubMed

Yiamouyiannis, C A; Stengel, P W; Cockerham, S L; Silbaugh, S A

1995-01-01

We examined the relationship between airway obstruction and plasma extravasation produced by the intravenous administration of the selective NK1 receptor agonist [Sar9, Met(O2)11]-substance P(SP). Conscious guinea-pigs were injected with Evans' blue dye followed by intravenous [Sar9,Met(O2)11]-SP. Animals were killed 3 min later and airway obstruction, determined via excised lung gas volumes, and plasma extravasation in the trachea, mainstem bronchi and intrapulmonary airways quantitated. Maximal plasma protein extravasation occurred at a dose about 30 times less than that required to elicit airway obstruction. Neither the neutral endopeptidase (NEP) inhibitor, thiorphan, or the angiotensin-converting enzyme (ACE) inhibitor, captopril, altered the extravasation response to [Sar9,Met(O2)11]-SP. However, thiorphan alone or combined with captopril produced a small but significant potentiation of the airway obstructive response. The marked difference between pulmonary gas trapping and Evans' blue extravasation responses suggest that [Sar9,Met(O2)11]-SP-induced airway obstruction is not secondary to increased pulmonary edema.

Studies on the trigeminal antidromic vasodilatation and plasma extravasation in the rat.

PubMed Central

Couture, R; Cuello, A C

1984-01-01

Antidromic stimulation of sensory peripheral branches of the trigeminal system (mental nerve) led to cutaneous vasodilatation and increased vascular permeability in rats anaesthetized with urethane. The antidromic vasodilatation observed in intact animals was not altered by decentralization or sympathectomy. Both antidromic vasodilatation and neurogenic plasma extravasation remained unaffected by pre-treatment with cimetidine, indomethacin, baclofen, guanethidine plus phentolamine and propranolol, but were significantly reduced by cimetidine plus mepyramine and atropine, suggesting that cholinergic and histaminergic components might be involved in the sensory neurogenic responses. Methysergide reduced only the extravasation, suggesting that probably serotonin liberated by mast cells upon sensory stimulation can contribute to the neurogenic responses. In tests using substance P (SP) antagonists (D-pro4, D- trp 7, 9, 10)-SP (4-11) and (D-pro2, D-trp 7, 9)-SP it was found that they are more active in reducing the neurogenic extravasation than the vasodilatation. In addition it was observed that (D-pro 4, D-trp 7, 9, 10)-SP (4-11) was the most potent substance P antagonist in reducing the plasma extravasation and antidromic vasodilatation resulting from sensory stimulation. PMID:6199494

Eliminating extravasation events: a multidisciplinary approach.

PubMed

Coyle, Christine E; Griffie, Julie; Czaplewski, Lynn M

2014-01-01

Administration of chemotherapy agents can give rise to many safety issues. Extravasation of a vesicant agent causes tissue blistering and necrosis. This complication of chemotherapy administration causes additional pain and suffering in patients who are already suffering with a diagnosis of cancer. Nurses hold key responsibilities for educating patients about administration issues and following practice standards to minimize the risk of extravasation. Defining a path of shared responsibilities among team members is a critical step in assuring the safe administration of drugs classified as vesicants. This article describes a clinical practice change that is used at a large midwestern academic medical cancer center. This practice and policy change has resulted in a 90% reduction in the administration of vesicant agents peripherally, with no occurrence of extravasations in the first 6 months of implementation.

Eliminating Extravasation Events: A Multidisciplinary Approach.

PubMed

Coyle, Christine E; Griffie, Julie; Czaplewski, Lynn M

2015-01-01

Administration of chemotherapy agents can give rise to many safety issues. Extravasation of a vesicant agent causes tissue blistering and necrosis. This complication of chemotherapy administration causes additional pain and suffering in patients who are already suffering with a diagnosis of cancer. Nurses hold key responsibilities for educating patients about administration issues and following practice standards to minimize the risk of extravasation. Defining a path of shared responsibilities among team members is a critical step in assuring the safe administration of drugs classified as vesicants. This article describes a clinical practice change that is used at a large midwestern academic medical cancer center. This practice and policy change has resulted in a 90% reduction in the administration of vesicant agents peripherally, with no occurrence of extravasations in the first 6 months of implementation.

Defining Tumor Cell and Immune Cell Behavior in Vivo during Pulmonary Metastasis of Breast Cancer

DTIC Science & Technology

2015-09-01

cancer cell extravasation , establishment and growth. PLoS One 4, e6562, doi:10.1371/journal.pone.0006562 (2009). 2 Qian, B. Z. et al. CCL2...cytoplast­ingesting cells behaved with respect to extravasation . We used i.v. injection of labelled anti­CD45 antibody15 to localize ZsGreen+ populations relative...to the vasculature at 4 and 24 h after injection. Consistent with previous data3, non­alveolar macrophages extravasated over this time period (Fig

Scintigraphic assessment of perivesical urinary extravasation following renal transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bushnell, D.L.; Wilson, D.G.; Lieberman, L.M.

Radionuclide scintigraphy is a safe and accurate means of detecting postoperative urologic complications in renal transplant recipients. Early identification of urinary leakage coupled with aggressive intervention significantly reduces the associated morbidity and mortality. Perivesical extravasate may be difficult to distinguish from adjacent or nearby bladder activity on scintiscan. Clarification of actual bladder contour and determination of its exact location within the pelvis may resolve such uncertainties. We describe imaging techniques that define the anatomic extent of the bladder and demonstrate our scintigraphic assessment of perivesical extravasation.

[Skin necrosis resulting from the extravasation of intravenous injections].

PubMed

Ikhefoulma, Soumaya; Mahiou, Abelhamid; Perillat, Isabelle

2012-09-01

Extravasation is the diffusion of a product injected intravenously into the perivascular or subcutaneous spaces. Skin necrosis of iatrogenic origin can be observed for example with a subcutaneous perfusion of solution containing potassium chloride or the extravasation of 30% hypertonic glucose serum. Whenever a product is injected, the administration route for which the product has obtained marketing authorisation must be respected and a perfusion time of at least 4 to 5 hours per litre of solution perfused must be observed.

Can the use of methylprednisolone, vitamin C, or alpha-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets?

PubMed

Farstad, M; Heltne, J K; Rynning, S E; Onarheim, H; Mongstad, A; Eliassen, F; Husby, P

2004-02-01

Hypothermic cardiopulmonary bypass is associated with capillary fluid leakage, resulting in edema and occasionally organ dysfunction. Systemic inflammatory activation is considered responsible. In some studies methylprednisolone has reduced the weight gain during cardiopulmonary bypass. Vitamin C and alpha-trinositol have been demonstrated to reduce the microvascular fluid and protein leakage in thermal injuries. We therefore tested these three agents for the reduction of cold-induced fluid extravasation during cardiopulmonary bypass. A total of 28 piglets were randomly assigned to four groups of 7 each: control group, high-dose vitamin C group, methylprednisolone group, and alpha-trinositol-group. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass was initiated in all animals and continued to 90 minutes. The fluid level in the extracorporeal circuit reservoir was kept constant at the 400-mL level and used as a fluid gauge. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit, and total water contents in different tissues were recorded, and the protein masses and the fluid extravasation rate were calculated. Hemodilution was about 25% after start of normothermic cardiopulmonary bypass. Cooling did not cause any further changes in hemodilution. During steady-state normothermic cardiopulmonary bypass, the fluid need in all groups was about 0.10 mL/(kg.min), with a 9-fold increase during the first 30 minutes of cooling (P <.001). This increased fluid need was due mainly to increased fluid extravasation from the intravascular to the interstitial space at a mean rate of 0.6 mL/(kg.min) (range 0.5-0.7 mL/[kg.min]; P <.01) and was reflected by increased total water content in most tissues in all groups. The albumin and protein masses remained constant in all groups throughout the study. Pretreatment with methylprednisolone, vitamin C, or alpha-trinositol was unable to prevent the increased fluid extravasation rate during hypothermic cardiopulmonary bypass. These findings, together with the stability of the protein masses throughout the study, support the presence of a noninflammatory mechanism behind the cold-induced fluid leakage seen during cardiopulmonary bypass.

Very Mild Hypothermia (35°C) Postischemia Reduces Infarct Volume and Blood/Brain Barrier Breakdown Following tPA Treatment in the Mouse.

PubMed

Cechmanek, Brian K; Tuor, Ursula I; Rushforth, David; Barber, Philip A

2015-12-01

Reperfusion therapies for stroke diminish in effectiveness and safety as time to treatment increases. Hypothermia neuroprotection for stroke is established, but its clinical translation has been hampered by uncertainties regarding optimal temperature and complications associated with moderate hypothermia. Also, hypothermia targeting temperatures of 32-33°C is associated with clinical and logistical problems related to induction and adverse side effects. We hypothesized that ischemic damage and tPA-exacerbated blood/brain barrier (BBB) breakdown produced following 30 minutes of middle cerebral artery occlusion and either 1 hour of saline or tPA infusion would be reduced by treatment with very mild cooling of 1.5°C for 48 hours followed by 24 hours of gradual rewarming. Infarct volume was reduced by 29.6% (p<0.001) and 41.9% (p<0.001) in hypothermic-tPA (Hypo_tPA)-treated and hypothermic-saline (Hypo_Sal)-treated animals compared to normothermic-tPA (Norm_tPA) and saline (Norm_Sal)-treated animals, respectively. Hypothermia also reduced IgG extravasation in tPA-treated, but not saline-treated groups compared to their normothermic controls (p<0.001). The ipsilateral-contralateral changes in optical density for IgG extravasation were 18.4% greater in the Norm_tPA than Norm_Sal (p<0.001) group. The ipsilateral-contralateral changes in optical density for IgG extravasation were reduced by 17.8% (p<0.001) in the Hypo_tPA compared to Norm_tPA group. No significant mean difference in IgG extravasation was seen between Hypo_tPA and Hypo_Sal groups (p>0.05). Very modest hypothermia to reduce the BBB breakdown could improve the availability and safety of reperfusion treatments for stroke.

Glutamine and alanyl-glutamine dipeptide reduce mesenteric plasma extravasation, leukocyte adhesion and tumor necrosis factor-α (TNF-α) release during experimental endotoxemia.

PubMed

Scheibe, R; Schade, M; Grundling, M; Pavlovic, D; Starke, K; Wendt, M; Retter, S; Murphy, M; Suchner, U; Spassov, A; Gedrange, T; Lehmann, Ch

2009-12-01

Glutamine (GLN) appears to be an essential nutrient during organism development and critical illness. The aim of our study was to evaluate the effects of GLN and its generic preparation alanyl-glutamine-dipeptide (DIP) on the microcirculation in endotoxemia in rats and its effects on tonus or aortal rings in vitro. Male Lewis rats (n=40) were separated in 4 groups. Group 1 (CON) served as healthy control group while the other groups received an endotoxin bolus i.v. (5 mg/kg lipopolysaccharide, LPS i.v.). In group 3 (LPS+GLN) 0.75 g/kg-1 GLN i.v. before LPS challenge was administered. In group 4 (LPS+DIP) DIP containing 0.75 g/kg GLN was given. Leukocyte-endothelial interactions and mesenteric plasma extravasation were determined at 0, 1 and 2 hours during the experiment by intravital fluorescence microscopy (IVM). Cytokine release (TNF-alpha, IL-1 beta, IL-6, IL-10) was measured by ELISA. GLN treatment reduced leukocyte adherence (-49.7% vs. LPS group, p<0.05) and plasma extravasation (-12.3% vs. LPS group, p<0.05) significantly during endotoxemia compared to untreated LPS animals. In group 4 (DIP+LPS), a decrease of leukocyte adherence (-56.0%) and mesenteric plasma extravasation (-18.8% vs. LPS group, p<0.05) was also found. TNF-alpha levels were reduced in both GLN and DIP (p<0.05). In vitro experiments demonstrated that glutamine agents could attenuate the response to contracting agents in presence of the vascular endothelium, implying nitric oxide pathway. In vivo, GLN as well as DIP pre-treatment diminish the detrimental impact of endotoxemia on the mesenteric microcirculation and the TNF-alpha release, the effects whose clinical importance should be further examined.

Detection of urinary extravasation by delayed technetium-99m DTPA renal imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taki, J.; Tonami, N.; Aburano, T.

Delayed imaging with Tc-99m DTPA renal scintigraphy demonstrated urinary extravasation in a patient with acute anuria in whom early sequential imaging showed no abnormal extrarenal radionuclide accumulation.

Skin necrosis due to antiblastics (procedures of prevention and therapy).

PubMed

Villani, C; Pace, S; Tomao, S; Pietrangeli, D; Pucci, G

1986-01-01

Among the toxic effects of antitumor drugs the injury for extravasation occurs too. The kinds of damage which result can achieve dramatic features with serious consequences on the psychophysic activity of patients who once tried other kinds of toxicity following chemotherapy. As the extravasation is caused by way of use and by drug-giving methods, we present this accident: it is necessary to observe rigorous rules of procedure during infusion and, if extravasation occurs, to make use of efficient drugs and physical methods. A recent case of extravasation occurred, at our Gynecological Oncology Service, in a patient who carried out chemotherapy without hospitalization. This case is here proposed and discussed; we think that the rarity of this accident is in our experience, due to the several precautions we observe during the infusion of drug.

Prevention of cytotoxic drug induced skin ulcers with dimethyl sulfoxide (DMSO) and alpha-tocopherole.

PubMed

Ludwig, C U; Stoll, H R; Obrist, R; Obrecht, J P

1987-03-01

Accidental subcutaneous extravasation of several antineoplastic agents may provoke skin ulcerations for which there has been no simple and effective treatment. Since January 1983 we have treated all patients in our institution sustaining extravasation by a cytotoxic drug with a combination of DMSO and alpha-Tocopherole. During the first 48 hr after extravasation a mixture of 10% alpha-Tocopherole acetate and 90% DMSO was topically applied. The bandage was changed every 12 hr. So far eight patients with extravasation of an anthracycline or Mitomycin were treated on this protocol. No skin ulceration, functional or neurovascular impairment occurred in any of these patients. The only toxic effect observed by this treatment was a minor skin irritation. The combination of DMSO and alpha-Tocopherole seems to prevent skin ulceration induced by anthracyclines and Mitomycin.

Nanomolar concentration of blood-soluble drag-reducing polymer inhibits experimental metastasis of human breast cancer cells

PubMed Central

Ding, Zhijie; Joy, Marion; Kameneva, Marina V; Roy, Partha

2017-01-01

Metastasis is the leading cause of cancer mortality. Extravasation of cancer cells is a critical step of metastasis. We report a novel proof-of-concept study that investigated whether non-toxic blood-soluble chemical agents capable of rheological modification of the near-vessel-wall blood flow can reduce extravasation of tumor cells and subsequent development of metastasis. Using an experimental metastasis model, we demonstrated that systemic administration of nanomolar concentrations of so-called drag-reducing polymer dramatically impeded extravasation and development of pulmonary metastasis of breast cancer cells in mice. This is the first proof-of-principle study to directly demonstrate physical/rheological, as opposed to chemical, way to prevent cancer cells from extravasation and developing metastasis and, thus, it opens the possibility of a new direction of adjuvant interventional approach in cancer. PMID:28280386

Complex upper arm reconstruction using an antero-lateral thigh free flap after an extravasation of Yttrium-90-ibritumomab Tiuxetan: A case report and literature review.

PubMed

Baus, A; Keilani, C; Bich, C-S; Entine, F; Brachet, M; Duhamel, P; Amabile, J-C; Malfuson, J V; Bey, E

2018-04-01

Yttrium-90-Ibritumomab Tiuxetan (Zevalin ® ) is used in the treatment of non- Hodgkin's lymphoma. Extravasation is an iatrogenic complication that is fortunately rare. However, the treatment of this complication is often complex due to the risk of extensive skin necrosis and unpredictable evolution of localized irradiation. This vesicant drug requires emergency management when extravasation occured. Radiations burns have specificities. Therefore, wound coverage involves specific plastic surgical techniques. Here, we report the case of a man presenting a chronic and extensive skin necrosis of upper arm treated with an antero-lateral thigh free flap. Moreover, we compare our experience of Zevalin ® extravasation management to other past publications and propose recommendations to prevent this unacceptable complication. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The cannabinoid receptor agonist WIN 55,212-2 inhibits antigen-induced plasma extravasation in guinea pig airways.

PubMed

Fukuda, Hironobu; Abe, Toshio; Yoshihara, Shigemi

2010-01-01

Although neurogenic inflammation of the airways via activation of C-fibers is thought to be important in the pathogenesis of asthma, the mechanisms regulating C-fiber activity remain uncertain. The influence of a cannabinoid receptor agonist, WIN 55,212-2, on C-fiber activation in guinea pig airways was investigated, as was the mechanism by which cannabinoids regulate antigen-induced airway inflammation. The inhibitory effect of WIN 55,212-2 on antigen-induced plasma extravasation was assessed in guinea pig tracheal tissues by photometric measurement of extravasated Evans blue dye after extraction with formamide. Pretreatment with WIN 55,212-2 (0.001, 0.01 or 0.1 mg/kg) significantly and dose-dependently reduced tracheal plasma extravasation induced by inhaling a 5% ovalbumin solution for 2 min after pretreatment with a neutral endopeptidedase inhibitor (phosphoramidon at 2.5 mg/kg i.v.). A cannabinoid CB2 receptor antagonist (SR144528) blunted the inhibitory effect of WIN 55,212-2, while a cannabinoid CB1 antagonist (SR141716A) did not. Pretreatment with a neurokinin-1 receptor antagonist (FK888) significantly reduced ovalbumin-induced extravasation of Evans blue dye. Pretreatment with the combination of WIN 55,212-2 and FK888 reduced antigen-induced plasma extravasation more markedly than FK888 alone. These findings suggest that WIN 55,212-2 inhibits C-fiber activation via the cannabinoid CB2 receptor and thus suppresses antigen-induced inflammation in guinea pig airways. 2010 S. Karger AG, Basel.

PO-12 - The key role of talin-1 in cancer cell extravasation dissected through human vascularized 3D microfluidic model.

PubMed

Gilardi, M; Bersini, S; Calleja, A Boussomier; Kamm, R D; Vanoni, M; Moretti, M

2016-04-01

Metastases are responsible for more than 90% of cancer related mortality. The hematogenous metastatic invasion is a complex process in which the endothelium plays a key role. Extravasation is a dynamic process involving remodeling and change in cell shape and in cytoskeleton whereby a series of strongly dependent interactions between CTCs and endothelium occurs [1]. Talins are proteins regulating focal adhesions and cytoskeleton remodeling. Talin-1 seems to be involved in the aggressiveness, motility, survival and invadopodia formation of cancer cells throughout the entire metastatic cascade [2], being up-regulated in breast cancer cells and mutated in sarcomas. Understand the implication of talin-1 in extravasation could facilitate the design of new therapies and finally fight cancer. We hypothesized that Talin-1 could be specifically involved in extravasation driving each of its steps. We developed a human 3D microfluidic model that enables the study of human cancer cell extravasation within a perfusable human microvascularized organ specific environment[3]. For the study of extravasation we applied microfluidic approach through the development of a microfluidic device in which endothelial cells and fibroblasts generated a 3D human functional vascular networks. Microvessel characterization was performed with immunofluorescence and permeability assays. We knocked-down talin-1 in triple negative breast cancer cell line MDA-MB231 and metastatic fibro-sarcoma cell line HT1080 with SiRNA and verified by Western-blot. Cancer cells were then perfused in the vessels and extravasation monitored through confocal imaging. We developed a human vascularized 3D microfluidic device with human perfusable capillary-like structures embedded in fibrin matrix, characterized by mature endothelium markers and physiological permeability (1.5±0.76)×10(-6) cm/s. We focused on the role of Talin-1 in adhesion to endothelium, trans-endothelial migration (TEM) and early invasion. Adhesion to the endothelium, TEM and migration within the ECM were monitored through confocal analyses. We demonstrated that Talin-1 KD significantly reduced the adhesion efficiency and TEM in both cell lines. Early invasion was also strongly and statistically reduced by the SiRNA treatment in both cell lines. We proved Talin-1 function in driving the extravasation mechanism in a human 3D vascularized environment. We demonstrated that Talin-1 is involved in each part of extravasation significantly affecting adhesion, TEM and the invasion stages. Targeting this protein could thus be an effective strategy to block metastasis. © 2016 Elsevier Ltd. All rights reserved.

Elucidation of the roles of tumor integrin β1 in the extravasation stage of the metastasis cascade

PubMed Central

Chen, Michelle B.; Lamar, John M.; Li, Ran

2016-01-01

Tumor integrin β1 (ITGB1) contributes to primary tumor growth and metastasis, but its specific roles have yet been clearly elucidated. In this study, we engineered an three-dimensional microfluidic model of the human microvasculature to recapitulate the environment wherein extravasation takes place and assess the consequences of β1 depletion in cancer cells. Combined with confocal imaging, these tools allowed us to decipher the detailed morphology of transmigrating tumor cells and associated endothelial cells in vitro at high spatio-temporal resolution not easily achieved in conventional transmigration assays. Dynamic imaging revealed that β1-depleted cells lacked the ability to sustain protrusions into the subendothelial matrix in contrast to control cells. Specifically, adhesion via α3β1 and α6β1 to subendothelial laminin was a critical prerequisite for successful transmigration. β1 was required to invade past the endothelial basement membrane, whereas its attenuation in a syngeneic tumor model resulted in reduced metastatic colonization of the lung, an effect not observed upon depletion of other integrin alpha and beta subunits. Collectively, our findings in this novel model of the vascularized tumor microenvironment revealed a critical requirement for β1 in several steps of extravasation, providing new insights into the mechanisms underlying metastasis. PMID:26988988

Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs.

PubMed

Parker, J C; Ivey, C L

1997-12-01

To separate the contributions of cellular and basement membrane components of the alveolar capillary barrier to the increased microvascular permeability induced by high pulmonary venous pressures (Ppv), we subjected isolated rat lungs to increases in Ppv, which increased capillary filtration coefficient (Kfc) without significant hemorrhage (31 cmH2O) and with obvious extravasation of red blood cells (43 cmH2O). Isoproterenol (20 microM) was infused in one group (Iso) to identify a reversible cellular component of injury, and residual blood volumes were measured to assess extravasation of red blood cells through ruptured basement membranes. In untreated lungs (High Ppv group), Kfc increased 6.2 +/- 1.3 and 38.3 +/- 15.2 times baseline during the 31 and 43 cmH2O Ppv states. In Iso lungs, Kfc was 36.2% (P < 0.05) and 64.3% of that in the High Ppv group at these Ppv states. Residual blood volumes calculated from tissue hemoglobin contents were significantly increased by 53-66% in the high Ppv groups, compared with low vascular pressure controls, but there was no significant difference between High Ppv and Iso groups. Thus isoproterenol significantly attenuated vascular pressure-induced Kfc increases at moderate Ppv, possibly because of an endothelial effect, but it did not affect red cell extravasation at higher vascular pressures.

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

PubMed

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

Genetic control of indirect airway responsiveness in the rat.

PubMed

Pauwels, R A; Germonpré, P R; Kips, J C; Joos, G F

1995-11-01

Many of the airway responses to endogenous and exogenous stimuli are caused by indirect mechanisms such as the activation of neurons and/or inflammatory cells. In the present study we compare the bronchoconstrictor and the plasma protein extravasation response to adenosine and tachykinins in two highly inbred rat strains, F344 and BDE. BDE-rats have a bronchoconstrictor response to adenosine at lower doses. Challenge with the A3-adenosine receptor agonist APNEA demonstrates that the difference in airway responsiveness to adenosine between BDE- and F344-rats is probably related to a higher number of A3-receptors on the airway mast cells of BDE-rats. In contrast, F344-rats have a higher airway responsiveness to tachykinins than BDE-rats. Tachykinins cause bronchoconstriction in F344-rats mainly by an indirect mechanism, involving stimulation of NK1-receptors and mast cell activation. In BDE-rats they cause bronchoconstriction by a direct effect on airway smooth muscle via activation of NK2-receptors. Finally we also observed a difference between F344- and BDE-rats with regard to the mechanisms involved in the plasma protein extravasation in the airways caused by substance P or capsaicin. In F344-rats but not in BDE-rats mast cell activation and the release of 5-hydroxytryptamine is partly responsible for this plasma protein extravasation.

[Introduction of a clinical protocol for extravasation at the National Institute of Oncology, Budapest, Hungary].

PubMed

Bartal, Alexandra; Mátrai, Zoltán; Rosta, András; Szûcs, Attila

2011-03-01

Extravasation of cytostatics occurs when an infusion containing a cytotoxic drug leaks into the surrounding perivascular and subcutaneous tissues. Incidence of cytostatic extravasation is found to be 0.1-6% according to the literature. Depending on the severity of complications, pain, loss of function in the extremities, or in extreme cases tissue necrosis necessitating an amputation may develop, drawing consequences like delay or interruption of the chemotherapy. Extent of complications is greatly influenced by the type of medication administered, general condition of the patient, and professional preparedness of staff providing the oncological health service. The protocol recently implemented in the National Institute of Oncology is a short, compact guidance for physicians and nurses providing oncological care, so by quick and adequate management of extravasation cases, severe complications could be prevented. More complex practical guidelines including algorithms could be created as a result of a wider collaboration, with the help of which oncological health professionals could easily cope with this rare problem. The authors describe in their review the implementation of the use of dry warm and cold packs, dymethylsulfoxide and hyaluronidase and their function within the algorithm of extravasation treatment.

Neonatal extravasation injury: prevention and management in Australia and New Zealand-a survey of current practice

PubMed Central

2013-01-01

Background Extravasation injury remains an important cause of iatrogenic injury in neonatal intensive care. This study aims to describe the current approach to extravasation injury (EI) prevention and management in Neonatal Intensive Care Units (NICUs) in Australia and New Zealand. Methods A literature review regarding extravasation injury in the newborn was carried out to inform questionnaire design. An internet-based survey was then conducted with the clinical directors of the 27 tertiary NICUs in Australia and New Zealand. Results The survey received a 96% response rate. Approximately two thirds of Australian and New Zealand NICUs have written protocols for prevention and management of extravasation injury. Considerable practice variation was seen for both prevention and treatment of EI. 92% of units had experienced cases of significant EI. Conclusions Australian and New Zealand tertiary neonatal units clearly recognise EI as an important cause of iatrogenic morbidity and mortality. Significant variation still exists among units with regards to guidelines for both prevention and management of EI. We recommend that neonatal staff should remain vigilant, ensuring that guidelines for the prevention and treatment of EI are available, and rigorously followed. PMID:23497004

Effect of quercetin on tachykinin-induced plasma extravasation in rat urinary bladder.

PubMed

Wille, P R; Ribeiro-do-Valle, R M; Simões, C M; Gabilan, N H; Nicolau, M

2001-08-01

The effect of quercetin on substance P-induced plasma extravasation in rat urinary bladder and its modulation by endogenous peptidases in conscious rats was studied. Plasma protein extravasation (PE) was assayed by measurement of extravasated Evans blue dye (microg/g dry tissue). Intravenous injection of substance P (SP, 10 nmol/kg) significantly increased PE in the urinary bladder. PE evoked by SP was increased significantly by quercetin (20 mg/kg, p.o.) pretreatment in the urinary bladder (73.5 +/- 4.9 to 152.2 +/- 9.9). Pretreatment with captopril, an angiotensin-converting enzyme (ACE) inhibitor (10 nmol/kg, i.v.), or with phosphoramidon, a neutral endopeptidase (NEP) inhibitor (2.5 micromol/kg, i.v.) also potentiated the SP-induced PE in urinary bladder, 286.2 +/- 20.4 and 323.3 +/- 34.0, respectively. Quercetin did not show any effect on neurokinin-A (NKA, 10 nmol/kg, i.v.) -induced plasma extravasation. The present study demonstrates that quercetin potentiates the PE induced by substance P in the urinary bladder. These effects suggest that this flavonoid might cause inhibition of NEP and/or ACE. Copyright 2001 John Wiley & Sons, Ltd.

Preventing extravasation injuries in neonates.

PubMed

Tong, Rachael

2007-10-01

Sick and preterm neonates are particularly vulnerable to extravasation injury but many of these injuries could be prevented if a 'hyper-vigilant' approach to monitoring of the intravenous access is adopted. A number of barriers exist that may prevent rigorous and continuous monitoring of intravenous access sites in neonatal units. Several themes were identified in the literature as supporting quality nursing practice in this area, including: staffing and skill mix, preceptorship of newly qualified staff, continuing professional development, record keeping and communication. These themes are explored and recommendations made to help reduce the incidence of extravasation injury.

Crossing the endothelial barrier during metastasis.

PubMed

Reymond, Nicolas; d'Água, Bárbara Borda; Ridley, Anne J

2013-12-01

During metastasis, cancer cells disseminate to other parts of the body by entering the bloodstream in a process that is called intravasation. They then extravasate at metastatic sites by attaching to endothelial cells that line blood vessels and crossing the vessel walls of tissues or organs. This Review describes how cancer cells cross the endothelial barrier during extravasation and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process. Identification of the mechanisms that underlie cancer cell extravasation could lead to the development of new therapies to reduce metastasis.

Rapid Bolus Administration Does not Increase The Extravasation Rate of Albumin: A Randomized Controlled Trial in The Endotoxemic Pig.

PubMed

von Seth, Magnus; Lipcsey, Miklós; Engström, Peter; Larsson, Anders; Hillered, Lars; Maripuu, Enn; Widström, Charles; Sjölin, Jan

2017-04-01

Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL × kg 5% albumin labeled with Technetium-99m, either as a rapid 15-min bolus (Bolus group, n = 16) or as a 2-h infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate, and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney, and lung was analyzed post mortem.The plasma area under the curve activity0-6 h was 4.4 ± 0.9 × 10 in the Bolus group and 4.4 ± 1.1 × 10 counts × min × mL × h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine, or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.

Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat.

PubMed

Miao, F J; Benowitz, N L; Heller, P H; Levine, J D

1997-01-01

1. In this study, we examined the mechanism(s) by which s.c. nicotine inhibits synovial plasma extravasation. We found that nicotine dose-dependently inhibited bradykinin (BK)- and platelet activating factor (PAF)-induced plasma extravasation. 2. The effect of nicotine on both BK- and PAF-induced plasma extravasation was attenuated by adrenal medullectomy. ICI-118,551 (a selective beta 2-adrenoceptor blocker) (30 micrograms ml-1, intra-articularly) significantly attenuated the inhibitory action of high-dose (1 mg kg-1) nicotine on BK-induced plasma extravasation without affecting the inhibition by low- (0.01 microgram kg-1) dose nicotine or that on PAF-induced plasma extravasation by nicotine at any dose. This suggested that beta 2-adrenoceptors mediate the inhibitory actions of high-dose, but not low-dose, nicotine. We also found that systemic naloxone (an opioid receptor antagonist) (two hourly injections of 1 mg kg-1, i.p.) attenuated the inhibitory action produced by all doses of nicotine on BK- or PAF-induced plasma extravasation, suggesting the contribution of endogenous opioids. 3. RU-38,486 (a glucocorticoid receptor antagonist) (30 mg kg-1, s.c.), and metyrapone (a glucocorticoid synthesis inhibitor) (two hourly injections of 100 mg kg-1, i.p.) both attenuated the action of high-dose nicotine without affecting that of low-dose nicotine. 4. Spinal mecamylamine (a nicotinic receptor antagonist) (0.025 mg kg-1, intrathecally, i.t.) attenuated the action of high-dose, but not low-dose, nicotine, suggesting that part of the action of high-dose nicotine is mediated by spinal nicotinic receptors. 5. Combined treatment with ICI-118,551, naloxone and RU-38,486 attenuated the action of low-dose nicotine by an amount similar to that produced by naloxone alone but produced significantly greater attenuation of the effect of high-dose nicotine when compared to the action of any of the three antagonists alone.

Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat

PubMed Central

Jia-Pei Miao, Frederick; Benowitz, Neal L; Heller, Philip H; Levine, Jon D

1997-01-01

In this study, we examined the mechanism(s) by which s.c. nicotine inhibits synovial plasma extravasation. We found that nicotine dose-dependently inhibited bradykinin (BK)- and platelet activating factor (PAF)-induced plasma extravasation. The effect of nicotine on both BK- and PAF-induced plasma extravasation was attenuated by adrenal medullectomy. ICI-118,551 (a selective β2-adrenoceptor blocker) (30 μg ml−1, intra-articularly) significantly attenuated the inhibitory action of high-dose (1 mg kg−1) nicotine on BK-induced plasma extravasation without affecting the inhibition by low- (0.01 μg kg−1) dose nicotine or that on PAF-induced plasma extravasation by nicotine at any dose. This suggested that β2-adrenoceptors mediate the inhibitory actions of high-dose, but not low-dose, nicotine. We also found that systemic naloxone (an opioid receptor antagonist) (two hourly injections of 1 mg kg−1, i.p.) attenuated the inhibitory action produced by all doses of nicotine on BK- or PAF-induced plasma extravasation, suggesting the contribution of endogenous opioids. RU-38,486 (a glucocorticoid receptor antagonist) (30 mg kg−1, s.c.) and metyrapone (a glucocorticoid synthesis inhibitor) (two hourly injections of 100 mg kg−1, i.p.) both attenuated the action of high-dose nicotine without affecting that of low-dose nicotine. Spinal mecamylamine (a nicotinic receptor antagonist) (0.025 mg kg−1, intrathecally, i.t.) attenuated the action of high-dose, but not low-dose, nicotine, suggesting that part of the action of high-dose nicotine is mediated by spinal nicotinic receptors. Combined treatment with ICI-118,551, naloxone and RU-38,486 attenuated the action of low-dose nicotine by an amount similar to that produced by naloxone alone but produced significantly greater attenuation of the effect of high-dose nicotine when compared to the action of any of the three antagonists alone. PMID:9117123

Risk management of extravasation of cytostatic drugs at the Adult Chemotherapy Outpatient Clinic of a university hospital.

PubMed

Adami, Nilce Piva; de Gutiérrez, Maria Gaby Rivero; da Fonseca, Selma Montosa; de Almeida, Elizabeth Pinto Magalhães

2005-08-01

To verify the incidence of extravasation of cytostatic drugs in patients treated on an outpatient basis at a university hospital in the city of São Paulo, Brazil, during the period from 1998 to 2002, and to assess the quality of care provided by the nursing team using a protocol adopted for the treatment of this adverse event as a parameter. The movement for quality in healthcare services has been a recent event in Brazil, mainly as the result of the Brazilian Program of Hospital Accreditation instituted in 1998. Considering the emphasis on risk management, it is important to mention the monitoring of the occurrence of extravasations of cytostatic drugs in order to improve the quality of nursing care provided to cancer patients. An evaluative study with a descriptive, prospective and longitudinal design was conducted, based on the documentary analysis of the notification of 216 extravasations of vesicant and irritant drugs that occurred between 1998 and 2002 and the corresponding prescriptions of cold or hot compresses. The mean incidence of extravasations ranged from 0.2 to 1.4% over the five years of the study. Incorrect prescription of the type of compress was observed for three patients. Undesired effects were ulcers caused by the extravasation of vinblastine and dacarbazine in two cases. The low incidence of both extravasation and tissue damage demonstrates the adequate quality of nursing care provided to cancer patients at the outpatient clinic studied. However, the identification of the lack of 12 records of thermal treatment and of three erroneous prescriptions requires the implementation of educational measures to prevent these types of incident. The relevance of this study to clinical practice is to increase the awareness and involvement of the nursing team in the maintenance of a continuous surveillance system of the process and results of chemotherapy administration in order to increase the quality of care and the safety of the patient.

Effect of platelet activating factor on endothelial permeability to plasma macromolecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Handley, D.A.; Arbeeny, C.M.; Lee, M.L.

The effect of intrajugular administration of platelet activating factor (PAF-C16) on vascular permeability was examined in the guinea pig. To examine the loss of selective endothelial permeability, the extravasative effect of PAF was assessed by monitoring hemoconcentration and the plasma loss of /sup 125/I-albumin (6.7 nm), /sup 125/I-low density lipoproteins (22.0 nm) or /sup 125/I-very low density lipoproteins (62.1 nm). Extravasation was dose-dependent and began 1 min after PAF administration, continuing for 5-7 min. During extravasation, there was no evidence for selective plasma retention of any of the labeled plasma tracers, as measured by plasma radioactivity. These results suggest thatmore » PAF-induced extravasation is dose-dependent, with increases in vascular permeability sufficient to permit similar plasma efflux rates of albumin, low density lipoproteins and very low density lipoproteins.« less

Neutrophils suppress intraluminal NK-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells

PubMed Central

Spiegel, Asaf; Brooks, Mary W.; Houshyar, Samin; Reinhardt, Ferenc; Ardolino, Michele; Fessler, Evelyn; Chen, Michelle B.; Krall, Jordan A.; DeCock, Jasmine; Zervantonakis, Ioannis K.; Iannello, Alexandre; Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Kamm, Roger D.; Pittet, Mikael J.; Raulet, David H.; Weinberg, Robert A.

2016-01-01

Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b+/Ly6G+ neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL-1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their crosstalk with host cells and disseminating carcinoma cells. PMID:27072748

Extravasation of paclitaxel into breast tissue from central catheter port.

PubMed

Barutca, Sabri; Kadikoylu, Gurhan; Bolaman, Zahit; Meydan, Nezih; Yavasoglu, Irfan

2002-10-01

A 53-year-old woman with advanced-stage ovarian cancer experienced extravasation of paclitaxel into the breast tissue as a result of inappropriate needle insertion and/or dislodgement; it came from a central catheter port (CCP) that was found to be intact under radiological examination with contrast material. The breast became tender and oedematous with erythema, and local warming was observed within a few hours. The patient improved in the next few days during nonsteroidal anti-inflammatory medication and close observation, and the breast healed with thickened and darkened skin and central scarring in the 6th month of follow-up. To the best of our knowledge, extravasation into breast tissue is rare in the literature. Extravasation of vesicant drugs from CCP can cause tissue necrosis; it is therefore essential that ports be carefully assessed and used by experienced staff to lessen the likelihood of such an unpleasant complication.

Extravasation of polymeric nanomedicines across tumor vasculature.

PubMed

Danquah, Michael K; Zhang, Xin A; Mahato, Ram I

2011-07-18

Tumor microvasculature is fraught with numerous physiological barriers which hinder the efficacy of anticancer agents. These barriers include chaotic blood supply, poor tumor vasculature permeability, limited transport across the interstitium due to high interstitial pressure and absence of lymphatic network. Abnormal microvasculature also leads to hypoxia and acidosis which limits effectiveness of chemotherapy. These barriers restrict drug or drug carrier extravasation which hampers tumor regression. Targeting key features of the tumor microenvironment such as tumor microvessels, interstitial hypertension and tumor pH is a promising approach to improving the efficacy of anticancer drugs. This review highlights the current knowledge on the distinct tumor microenvironment generated barriers which limit extravasation of drugs and focuses on modalities for overcoming these barriers using multi-functional polymeric carriers. Special attention is given to utilizing polymeric nanomedicines to facilitate extravasation of anticancer drugs for future cancer therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

[Dexrazoxane in anthracycline induced cardiotoxicity and extravasation].

PubMed

Goey, Andrew K L; Schellens, Jan H M; Beijnen, Jos H; Huitema, Alwin D R

2010-01-01

Cardiotoxicity and extravasation injuries are extremely serious complications of anthracycline use. Both complications are probably caused by oxidative stress. Dexrazoxane has been approved as a cardioprotective agent and as an antidote in extravasation of anthracyclines. Randomized clinical trials have shown that dexrazoxane is the only cardioprotective agent proven to be effective in the treatment of anthracycline-induced cardiotoxicity. In these clinical studies dexrazoxane decreased the incidence of cardiac events and heart failure. Possible adverse effects of dexrazoxane when administered as a cardioprotective agent are a decreased antitumor effect of anthracyclines and the onset of secondary malignancies in children. As an antidote in anthracycline extravasation, clinical studies showed dexrazoxane to be highly efficacious in preventing the need for surgical resection. Dexrazoxane can be considered as the treatment of first choice for this indication. Dexrazoxane is well tolerated in general. The most commonly reported side effects are leukopenia, thrombocytopenia and local reactions at the infusion site.

Extravasation of a therapeutic dose of 131I-metaiodobenzylguanidine: prevention, dosimetry, and mitigation.

PubMed

Bonta, Dacian V; Halkar, Raghuveer K; Alazraki, Naomi

2011-09-01

After the extravasation of a therapeutic dose of (131)I-metaiodobenzylguanidine that produced a radiation burn to a patient's forearm, we instituted a catheter placement verification protocol. Before therapy infusion, proper placement is verified by administering 37 MBq of (99m)Tc-pertechnetate through the catheter, and monitoring activity at the administration site and on the contralateral extremity. A dosimetric model describing both high-rate and low-rate dose components was developed and predicted that the basal epidermal layer received a radiation dose consistent with the observed moist desquamation radiation skin toxicity. No extravasation incidents have occurred since the verification procedure was instituted. To protect against radiation injury from extravasation of therapeutic radionuclides, test administration of a small (99m)Tc dose with probe monitoring of comparable sites in both upper extremities appears to be an effective preventive measure.

[The significance of extravasation in oncological care].

PubMed

Zatkóné Puskás, Gabriella

2008-03-01

The treatment of cancer may be associated with various chemotherapy-induced mucocutaneous reactions. One of the mucocutaneous adverse effects of antineoplastic drugs is the toxic local tissue reaction, the extravasation, which occurs in less than 1-2% of cytotoxic infusions. The standard management of vesicant extravasation includes: discontinuing all local infusions, aspiration of any residual drug, elevating the involved limb, local cooling or warm compresses, local anesthesia, antidotes (sodium thiosulfate for alkylating agents, dimethylsulfoxide (DMSO) for anthracyclines and mitomycin, and hyaluronidase for the vinca alkaloids), and finally surgical debridement with plastic surgery reconstruction. Because the anthracyclines are topoisomerase II poisons that are antagonized by topoisomerase II catalytic inhibitors such as dexrazoxane, it seems to be the treatment of choice immediately after extravasation of doxorubicin, epirubicin, daunorubicin, etc. One systemic dose of dexrazoxane after the accident may significantly reduce the toxic tissue lesions. Repeated intralesional injections of GM-CSF may accelerate the wound healing without the need of skin grafts.

Epidemiological survey of mucus extravasation phenomenon at an oral pathology referral center during a 43 year period.

PubMed

Bezerra, Thâmara Manoela Marinho; Monteiro, Bárbara Vanessa de Brito; Henriques, Águida Cristina Gomes; de Vasconcelos Carvalho, Marianne; Nonaka, Cassiano Francisco Weege; da Costa Miguel, Márcia Cristina

2016-01-01

Mucoceles are common benign pseudocystic lesions of the oral cavity; their main etiological factors are trauma and ductal obstruction. Two histological patterns are found: mucus retention phenomenon (MRP) and mucus extravasation phenomenon (MEP). Mucus extravasation phenomenon is the more common histological subtype and it mainly affects the lower lip. The knowledge of its main clinical features and management is important to assist health professionals in clinical practice. This study aimed to determine the relative frequency and distribution of oral mucoceles in an oral pathology reference center. Cross-sectional historical study that analyzed all cases pathologically diagnosed as mucus extravasation phenomenon by the department of anatomic pathology of an oral pathology referral center from June of 1970 to May of 2014, considering the clinical characteristics of the lesion and those relating to the patient. SPSS v. 20.0 software for Windows was used for descriptive analysis. During 43 years, 719 cases of mucus extravasation phenomenon (54.7% men and 45.3% women) were registered, with the lower lip as the most commonly affected site (n=484; 67.3%). The average age of patients was 20.8 years (SD±14.4) with a peak occurrence in the second decade of life. Most professionals had oral mucocele/ranula (n=606; 84.3%) as the initial clinical impression. Mucus extravasation phenomenon is a lesion that primarily affects young patients, affecting mainly the lower lip, and is commonly found in oral diagnostic services. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Contrast Extravasation versus Hemorrhage after Thrombectomy in Patients with Acute Stroke.

PubMed

Yedavalli, Vivek; Sammet, Steffen

2017-11-01

Intra-arterial recanalization postprocedural imaging in stroke patients can result in diagnostic complications due to hyperdensities on noncontrast computed tomography (CT), which may represent either contrast extravasation or intracranial hemorrhage. If these lesions are hemorrhage, then they are risk factors becoming symptomatic, which, if not distinguished, can alter clinical management. We investigate the effects of iodinated contrast on postprocedural magnetic resonance imaging (MRI) and prevalence of equivocal imaging interpretations of postprocedural extravasated contrast versus hemorrhage while identifying protocol pitfalls. We identified 10 patients diagnosed with ischemic stroke who underwent intra-arterial recanalization in a 5-year period. These patients demonstrated a hyperdensity on a postprocedural CT within 24 hours, underwent an MRI within 48 hours, and an additional confirmatory noncontrast CT at least 72 hours postprocedure. Postprocedural MRI in all 10 stroke patients demonstrated T 1 - and T 2 -relaxation time changes due to residual iodine contrast agents. This lead to false positive postprocedural hemorrhage MRI interpretations in 2/10 patients, 3/10 false negative interpretations of contrast extravasation, and 5/10 equivocal interpretations suggesting extravasation or hemorrhage. Of these five cases, two were performed with gadolinium. MRI done within 48 hours postprocedure can lead to false positive hemorrhage or false negative contrast extravasation interpretations in stroke patients possibly due to effects from the administered angiographic contrast. Additionally, MRI should be done both after 72 hours for confirmation and without gadolinium contrast as the effects of the gadolinium contrast and residual angiographic contrast could lead to misdiagnosis. Copyright © 2017 by the American Society of Neuroimaging.

Anterior thalamic nuclei deep brain stimulation reduces disruption of the blood-brain barrier, albumin extravasation, inflammation and apoptosis in kainic acid-induced epileptic rats.

PubMed

Chen, Ying-Chuan; Zhu, Guan-Yu; Wang, Xiu; Shi, Lin; Du, Ting-Ting; Liu, De-Feng; Liu, Yu-Ye; Jiang, Yin; Zhang, Xin; Zhang, Jian-Guo

2017-12-01

Objective The therapeutic efficacy of anterior thalamic nuclei deep brain stimulation (ATN-DBS) against seizures has been largely accepted; however, the effects of ATN-DBS on disruption of the blood-brain barrier (BBB), albumin extravasation, inflammation and apoptosis still remain unclear. Methods Rats were distributed into four treatment groups: physiological saline (PS, N = 12), kainic acid (KA, N = 12), KA-sham-DBS (N = 12) and KA-DBS (N = 12). Seizures were monitored using video-electroencephalogram (EEG). One day after surgery, all rats were sacrificed. Then, samples were prepared for quantitative real-time PCR (qPCR), western blot, immunofluorescence (IF) staining, and transmission electron microscopy to evaluate the disruption of the BBB, albumin extravasation, inflammation, and apoptosis. Result Because of the KA injection, the disruption of the BBB, albumin extravasation, inflammation and apoptosis were more severe in the KA and the KA-sham-DBS groups compared to the PS group (all Ps < 0.05 or < 0.01). The ideal outcomes were observed in the KA-DBS group. ATN-DBS produced a 46.3% reduction in seizure frequency and alleviated the disruption of the BBB, albumin extravasation, inflammatory reaction and apoptosis in comparison to the KA-sham-DBS group (all Ps < 0.05 or < 0.01). Conclusion (1) Seizures can be reduced using ATN-DBS in the epileptogenic stage. (2) ATN-DBS can reduce the disruption of the BBB and albumin extravasation. (3) ATN-DBS has an anti-inflammatory effect in epileptic models.

The efficacy of negative pressure wound therapy on chemotherapeutic extravasation ulcers: An experimental study.

PubMed

Iscı, Evren; Canter, Halil I; Dadacı, Mehmet; Atılla, Pergin; Cakar, Ayse N; Kecık, Abdullah

2014-01-01

The extravasation of the chemotherapeutic agents is not an unusual phenomenon. Necrosis of the skin and underlying structures has been reported, depending on the cytotoxicity of the extravasating drug. Despite the presence of some antidotes, such wounds tend to enlarge with time and are likely to resist the treatment. The objective of this study was to investigate the efficacy of negative pressure wound therapy (NPWT) on extravasation ulcers. Animals were separated into two groups; conventional dressing group and NPWT group. Extravasation necrosis was established by intradermal doxorubicin injection. Following the debridement of the necrotic areas, one group of animals was treated with the conventional dressing while NPWT was applied to the other group. The wound areas were measured, and then biopsies were taken on the 3(rd), 7(th) and 14(th) days after the debridement. SPSS 11.5 for Windows was used. Two-way ANOVA test was used to compare wound areas between groups. Willcoxon sign test with Bonferroni correction was used to compare histological scores between groups. Chi-square test with Bonferroni correction was used to compare histological scores within the group between the days. There is no significant difference in terms of inflammatory cell count, neovascularisation, granulation tissue formation between the groups. Contrary to these results wound areas at the end of the treatment were smaller in the NPWT group compared with the dressing group. There is the superiority of NPWT over conventional dressing in chemotherapeutic extravasation wounds as well as the wound area is concerned, but it is not proven histologically.

Focused ultrasound and microbubbles for enhanced extravasation.

PubMed

Böhmer, M R; Chlon, C H T; Raju, B I; Chin, C T; Shevchenko, T; Klibanov, A L

2010-11-20

The permeability of blood vessels for albumin can be altered by using ultrasound and polymer or lipid-shelled microbubbles. The region in which the microbubbles were destroyed with focused ultrasound was quantified in gel phantoms as a function of pressure, number of cycles and type of microbubble. At 2MPa the destruction took place in a fairly wide area for a lipid-shelled agent, while for polymer-shelled agents at this setting, distinct destruction spots with a radius of only 1mm were obtained. When microbubbles with a thicker shell were used, the pressure above which the bubbles were destroyed shifts to higher values. In vivo both lipid and polymer microbubbles increased the extravasation of the albumin binding dye Evans Blue, especially in muscle leading to about 6-8% of the injected dose to extravasate per gram muscle tissue 30 min after start of the treatment, while no Evans Blue could be detected in muscle in the absence of microbubbles. Variation in the time between ultrasound treatment and Evans Blue injection, demonstrated that the time window for promoting extravasation is at least an hour at the settings used. In MC38 tumors, extravasation already occurred without ultrasound and only a trend towards enhancement with about a factor of 2 could be established with a maximum percentage injected dose per gram of 3%. Ultrasound mediated microbubble destruction especially enhances the extravasation in the highly vascularized outer part of the MC38 tumor and adjacent muscle and would, therefore, be most useful for release of, for instance, anti-angiogenic drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

Implementation of a protocol for the prevention and management of extravasation injuries in the neonatal intensive care patient.

PubMed

Warren, Diane

2011-06-01

This project sought to determine nurses' understanding and management of infants with intravenous (IV) therapy. There were three specific aims: • To improve identification and management of extravasation injuries in neonates • To ensure management of extravasation injuries in neonates is classified according to IV extravasation staging guidelines • To develop a protocol that outlined actions required to manage extravasation injuries. This project utilised a pre- and post-implementation audit strategy using the Joanna Briggs Institute (JBI) Getting Research into Practice (GRIP) program. This method has been used to improve clinical practice by utilising an audit, feedback and re-audit sequence. The project was implemented in four stages over a 7-month period from 21 October 2009 to 30 May 2010. Initially, there was poor compliance with all four criteria, ranging from zero to 63%. The GRIP phase of the project identified five barriers which were addressed throughout this project. These related to education of staff and the development of a protocol for the prevention and management of extravasation injuries in the neonatal population. Following implementation of best practice, the second audit showed a marked improvement in all four criteria, ranging from 70 to 100% compliance. Overall, this project has led to improvements in clinical practice in line with current evidence. This has resulted in enhanced awareness of the risks associated with IV therapy and of measures to prevent an injury occurring within this clinical setting. © 2011 The Author. International Journal of Evidence-Based Healthcare © 2011 The Joanna Briggs Institute.

The development of a pseudo-chamber after balloon pulmonary angioplasty: long-term complications of balloon pulmonary angioplasty.

PubMed

Sugiyama, Hisashi; Kise, Hiroaki; Toda, Takako; Hoshiai, Minako

2016-11-01

We experienced a rare complication where extravasation developed a pseudo-chamber long after the balloon pulmonary angioplasty for supravalvular pulmonary stenosis. A 3-month-old girl was diagnosed with an anomalous origin of the left coronary artery from the pulmonary artery. She underwent the Takeuchi procedure at 10 months of age. During the follow-up, the supravalvular pulmonary stenosis deteriorated, and was treated by balloon pulmonary angioplasty with the double balloon technique catheter at 6 years of age. Angiography at the main pulmonary artery showed a small amount of extravasation contrast medium after the procedure. Follow-up echocardiography showed a diminished extravasation hemorrhage. Twelve years later, right ventricular enlargement due to pulmonary regurgitation had been observed on echocardiography. In addition, abnormal echo free space was detected at the left posterior of the left atrium. Enhanced computed tomography clearly demonstrated there was an orifice and extent of the pseudo-chamber. Surgical findings revealed a large tear just distal to the coronary tunnel. We speculated that extravasation blood was limited in the perivascular area early after the procedure but eventually reached the non-adhesive oblique pericardial sinus with age. Consequently, pulmonary to oblique pericardial sinus communication was established and looked like a pseudo-chamber long after the procedure. In conclusion, even if extravasation seems to be limited immediately after the balloon pulmonary angioplasty, it could expand for non-adhesive space and could develop a huge blood space like chamber. Long-term careful observation should be necessary for extravasation of pulmonary artery even with surgical adhesion.

Specific neurokinin receptors mediate plasma extravasation in the rat knee joint.

PubMed Central

Lam, F. Y.; Ferrell, W. R.

1991-01-01

1 Plasma extravasation in the rat knee joint was induced by intra-articular injection of neurokinins and specific neurokinin receptor agonists. 2 Pronounced plasma extravasation was produced by substance P (SP, 4-185 microM) and to a lesser extent by neurokinin-B (NKB, 83-413 microM), whereas neurokinin-A (NKA, 88-440 microM) and calcitonin gene-related peptide (CGRP, 26-130 microM) had no significant effect. 3 The specific neurokinin1 receptor agonist [Sar9, Met(O2)11]-substance P (NK1 agonist) in doses of 0.4-70 microM appeared to be more potent than SP in eliciting plasma extravasation. The neurokinin2 receptor agonist [Nle10]-neurokinin A4-10 (NK2 agonist) was not effective at 70 microM but produced a small and significant effect at 330 microM, whereas the neurokinin3 receptor agonist [MePhe7]-neurokinin B (NK3 agonist) was without effect at 40 microM or 400 microM. 4 Injections of SP or NKA into the synovial cavity of the rat knee were equally effective in producing marked plasma extravasation in remote sites such as the forelimb and hindlimb paws. 5 Co-administration experiments showed that the effects of SP were synergistic with NKA or the NK1 receptor agonist, but not with CGRP or the NK2 receptor agonist. 6 The rank order of potency was NK1 agonist greater than or equal to SP greater than NKB greater than NK2 agonist suggesting that NK1 receptors mediate plasma extravasation in the rat knee joint. PMID:1715229

Impact of cell-free hemoglobin on contracting skeletal muscle microvascular oxygen pressure dynamics.

PubMed

Ferguson, Scott K; Harral, Julie W; Pak, David I; Redinius, Katherine M; Stenmark, Kurt R; Schaer, Dominik J; Buehler, Paul W; Irwin, David C

2018-06-01

Free hemoglobin (Hb) associated with hemolysis extravasates into vascular tissue and depletes nitric oxide (NO), which leads to impaired vascular function and could impair skeletal muscle metabolic control during exercise. We tested the hypothesis that: 1) free Hb would extravasate into skeletal muscle tissue, reducing the contracting skeletal muscle O 2 delivery/O 2 utilization ratio (microvascular PO 2 , PO 2 mv) to a similar extent as that observed following NO synthase (NOS) blockade, and 2) that the Hb scavenging protein haptoglobin (Hp) would prevent Hb extravasation and inhibit these skeletal muscle tissue effects. PO 2 mv was measured in eight rats (phosphorescence quenching) at rest and during 180 s of electrically induced (1-Hz) twitch spinotrapezius muscle contractions (experiment 1). A second group of seven rats was also used to investigate the effects of Hb + Hp (experiment 2). For both experiments, measurements were made: 1) during control conditions, 2) following a bolus infusion of either Hb (50 mg/kg) or Hb + Hp (50 mg/kg), and 3) following local superfusion of NG-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg). Additional experiments were completed to visualize Hb extravasation into the muscular tissue using Click chemistry techniques. There were no significant differences in the PO 2 mv observed at rest for any condition in either experiment (p > 0.05 for all). In experiment 1, both Hb and L-NAME reduced the PO 2 mv significantly during the steady-state of muscle contractions when compared to control conditions with no differences between Hb and L-NAME (control: 24 ± 1, Hb: 21 ± 1, L-NAME: 20 ± 1 mmHg, p < 0.05). In experiment 2, only L-NAME resulted in a significantly lower PO 2 mv during the steady-state of muscle contractions (control: 25 ± 1, Hb + Hp: 22 ± 2, L-NAME: 18 ± 1 mmHg, p < 0.05). Free Hb lowered the blood-myocyte O 2 driving force to a level not significantly different from L-NAME. However, infusing Hb bound to Hp resulted in no significant differences in steady-state PO 2 mv during muscle contractions when compared to control. Surprisingly, we did not observe Hb accumulation in skeletal muscle tissue. Taken together these data suggests that free Hb impairs O 2 delivery/utilization via a NO scavenging effect. Furthermore, the unchanged PO 2 mv steady-state observed following Hb + Hp further indicates that vascular compartmentalization of Hb by the scavenger protein haptoglobin may improve skeletal muscle metabolic control and potentially exercise tolerance in those afflicted with hemolytic diseases. Copyright © 2018. Published by Elsevier Inc.

Prevention of extravasation injuries secondary to doxorubicin.

PubMed

Linder, R M; Upton, J

1985-03-01

Intravenously administered drugs with potentially devastating consequences should be given only by personnel highly knowledgeable regarding the side effects and skilled in intravenous cannulation. A strict protocol should be followed. The earliest signs heralding extravasation should be recognized and infusion discontinued immediately. If extravasation occurs, prompt surgical consultation is necessary. Injection into the volar wrist, dorsum of the hand, and antecubital fossa should always be avoided. Polyethylene catheters are preferable to butterfly needles for administering chemotherapeutic agents. A careful history of the venous problems of patients who require long-term therapy should be maintained in their chart. Ideally, vascular access should avoid these problems.

Active extravasation of gadolinium-based contrast agent into the subdural space following lumbar puncture.

PubMed

Kothari, Pranay D; Hanser, Evelyn M; Wang, Harrison; Farid, Nikdokht

2016-01-01

A 38year-old male presented with cauda equina syndrome following multiple lumbar puncture attempts. Lumbar spine magnetic resonance imaging (MRI) showed a subdural hematoma and an area of apparent contrast enhancement in the spinal canal on sagittal post-contrast images. Axial post-contrast images obtained seven minutes later demonstrated an increase in size and change in shape of the region of apparent contrast enhancement, indicating active extravasation of the contrast agent. This is the first reported case of active extravasation of gadolinium-based contrast agent in the spine. Copyright © 2016 Elsevier Inc. All rights reserved.

Early intervention reduces morbidity in extravasation injuries from 'lighter fuel' injection.

PubMed

Thaha, M A; McKinnell, T H; Graham, K E; Naasan, A N

2007-01-01

Injection of 'lighter fuel' with suicidal intent is rare. Extravasation of the chemical may rarely cause systemic toxicity, but usually it results in extensive soft tissue damage. Such injuries when managed by the traditional expectant policy are associated with considerable morbidity. Early aggressive surgical management using 'saline flush out' limits the tissue damage by stopping the natural progression of the chemical mediated injury and the subsequent inflammatory response, thereby allowing better skin preservation and functional outcome in these cases. We report a case of 'lighter fuel' subcutaneous extravasation injury managed by 'saline flush out' technique soon after presentation.

The management of cytotoxic chemotherapy extravasation: a systematic review of the literature to evaluate the evidence underpinning contemporary practice.

PubMed

Harrold, K; Gould, D; Drey, N

2015-11-01

Management of cytotoxic drug extravasation remains contentious, with differing views on the most effective management strategy. With the increasing drive to provide effective, evidence-based healthcare, while ensuring the patient experience of the treatment provided plays a significant part in the development of clinical practice guidelines, the purpose of this literature review was to both critically analyse the quality of evidence that underpins contemporary practice and to determine if the patient experience is taken into account. A literature search was undertaken sourcing publications from the 1960s to July 2014 identifying all studies detailing strategies aimed at preventing the need for surgical debridement and all studies evaluating extravasation management from the patient's perspective. No conclusive evidence was found to suggest one clinical strategy as more effective than the other. No studies were identified that evaluated outcome from the patient's perspective. It is therefore suggested that outcomes-based research should underpin contemporary extravasation management guidelines to determine what the final outcome or 'end result' is and how this impacts on the patient and that the current lack of research into the patient experience of extravasation management is an area that needs to be addressed. © 2015 John Wiley & Sons Ltd.

Extravasation of liposomal daunorubicin in patients with AIDS-associated Kaposi's sarcoma: a report of four cases.

PubMed

Cabriales, S; Bresnahan, J; Testa, D; Espina, B M; Scadden, D T; Ross, M; Gill, P S

1998-01-01

To report on four patients with AIDS-related Kaposi's sarcoma who were treated with liposomal daunorubicin (DaunoXome, NeXstar Pharmaceuticals, Inc., San Dimas, CA) as part of phase I/II and phase III clinical trials and who experienced extravasation during IV infusion. All patients were treated with ice as an immediate intervention. In addition, two patients received treatment with multiple subcutaneous injections of steroids. Two patients experienced erythema, swelling, and pain after the extravasation. Two patients who were treated aggressively reported erythema and swelling without pain. Three patients observed changes in the texture of their skin that was accompanied by decreased sensation, which developed after 8-16 weeks. These changes completely resolved in all patients receiving intervention after six months. None of the patients suffered tissue necrosis. Extravasation with liposomal daunorubicin is notable for the absence of tissue necrosis that typically is observed with anthracyclines. Long-term effects were limited to skin discoloration and decreased sensation, both of which resolved in all patients. The lack of observed skin necrosis with daunorubicin suggests a treatment advantage with a reduction in the required aggressive extravasation procedures for free anthracyclines as well as increased safety for the patient. Additional data is needed to confirm these observations.

Local anesthetics differentially inhibit sympathetic neuron-mediated and C fiber-mediated synovial neurogenic plasma extravasation.

PubMed

Pietruck, Christian; Grond, Stefan; Xie, Guo-Xi; Palmer, Pamela P

2003-05-01

Local anesthetics are used for local irrigation after many types of operations. However, recent evidence of toxic effects of local anesthetics at large concentrations during continuous administration suggests an advantage of using decreased local anesthetic concentrations for irrigation solutions. In this study, we determined whether smaller concentrations of local anesthetics may maintain an antiinflammatory and, therefore, analgesic effect without the risk of possible toxicity. Lidocaine and bupivacaine were studied for their ability to inhibit both components of neurogenic inflammation-C fiber-mediated and sympathetic postganglionic neuron (SPGN)-mediated inflammation-in the rat knee joint. Intraarticular lidocaine 0.02% reduced 5-hydroxytryptamine (5-HT)-induced (SPGN-mediated) plasma extravasation (PE) by 35%, and further decreases were obtained by perfusing larger concentrations of lidocaine. Intraarticular bupivacaine 0.025% inhibited 5-HT-induced PE by 60%, and a 95% inhibition was obtained with bupivacaine 0.05%. Larger local anesthetic concentrations were necessary to inhibit C fiber-mediated PE than those required to inhibit SPGN-mediated PE. Lidocaine 0.4% was required to reduce mustard oil-induced PE by 60%. Lidocaine 2% inhibited mustard oil-induced PE to baseline levels. Bupivacaine 0.1% was required for an 80% reduction of PE. Bupivacaine 0.25% inhibited mustard oil-induced PE to baseline levels. Our results demonstrate differential effects of local anesthetics on SPGN- and C fiber-mediated PE but confirm the concept of using smaller concentrations of local anesthetics to achieve inhibition of postoperative inflammation. Local anesthetic wound irrigation is often used to treat postoperative surgical pain. Large concentrations of local anesthetics are usually used, and these concentrations may have possible neurotoxic and myotoxic effects. Our results demonstrate antiinflammatory effects of lidocaine and bupivacaine at concentrations smaller than used clinically.

Biomarkers Prognostic for Elevated Intracranial Pressure

DTIC Science & Technology

2016-03-01

hematoma and active extravasation , for which she was taken emergently to interventional radiology for embolization of the bilateral internal iliac...approach to injuries was carried out. She was sent to IR for evaluation of her grade 3 liver laceration with active punctate extravasation and later

Extravasated platelet aggregation in liver zone 3 may correlate with the progression of sinusoidal obstruction syndrome following living donor liver transplantation: A case report

PubMed Central

NAKANUMA, SHINICHI; MIYASHITA, TOMOHARU; HAYASHI, HIRONORI; TAJIMA, HIDEHIRO; TAKAMURA, HIROYUKI; TSUKADA, TOMOYA; OKAMOTO, KOICHI; SAKAI, SEISHO; MAKINO, ISAMU; KINOSHITA, JUN; NAKAMURA, KEISHI; OYAMA, KATSUNOBU; INOKUCHI, MASAFUMI; NAKAGAWARA, HISATOSHI; NINOMIYA, ITASU; KITAGAWA, HIROHISA; FUSHIDA, SACHIO; FUJIMURA, TAKASHI; OHTA, TETSUO

2015-01-01

Sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease, is relatively rare subsequent to liver transplantation (LT). SOS refractory to medical therapy, however, can result in centrilobular fibrosis, portal hypertension and liver failure. Although sinusoidal endothelial cell damage around central venules (zone 3) occurs early in the development of SOS, the detailed mechanism of SOS development and its association with thrombocytopenia are not yet completely understood. The present report describes a patient who experienced SOS with unexplained thrombocytopenia following living donor LT. The progression of SOS resulted in graft dysfunction and the patient succumbed. The presence of platelets in the liver allograft was assayed immunohistochemically using antibody to the platelet marker cluster of differentiation 42b (platelet glycoprotein Ib). Platelet aggregates were found attached to hepatocytes along the sinusoid and within the cytoplasm of hepatocytes, particularly in zone 3. By contrast, no staining was observed in zone 1. These findings suggested that extravasated platelet aggregation in the space of Disse and the phagocytosis of platelets by hepatocytes were initiated by sinusoidal endothelial cell damage due to the toxicity of the immunosuppressant tacrolimus or a corticosteroid pulse, and that platelet activation and degranulation may be at least partially involved in the mechanism responsible for SOS. PMID:25780397

Contribution of B2 receptors for bradykinin in Arthus reaction-induced plasma extravasation in wild-type or B2 transgenic knockout mice

PubMed Central

Samadfam, R; Teixeira, C; Bkaily, G; Sirois, P; de Brum-Fernandes, A; D'Orleans-Juste, P

2000-01-01

The aim of the present study was to investigate the contribution of bradykinin (BK) B1 and B2 receptors in a model of type III hypersensitivity, the reverse passive Arthus reaction (RPA), in wild-type mice and transgenic B2 knockout littermates.BK (10 μg mouse−1) or bovine serum albumin (0.5 mg mouse−1) induced a sustained Evans blue extravasation for more than 80 min in naive or rabbit anti-bovine serum albumin-treated mice (RPA model), respectively. The response to the two stimuli was prevented by the B2 receptor antagonist, HOE-140, but not by [Leu8]desArg9-BK (B1 receptor antagonist).In contrast to the wild-type littermates, RPA and bradykinin were unable to trigger an increase in plasma extravasation in B2 knockout mice.Furthermore, endothelin-1 (5 μg mouse−1) and a selective NK-1 receptor agonist [Sar9,Met (O2)11]-SP (20 μg mouse−1), triggered a significant increase in peritoneal plasma extravasation in both wild-type and B2 knockout animals.A pretreatment with indomethacin (200 μg mouse−1) significantly reduced the RPA-induced but not the BK-induced increase in Evans blue extravasation. Furthermore, RPA, but not BK, triggered a significant indomethacin-sensitive increase in peritoneal prostaglandin E2 content.Our results suggest a pivotal role for B2 receptors in the mechanism of plasma extravasation which occurs during the reverse passive Arthus reaction in the mouse. Moreover, our results suggest an important contribution of prostanoids in the plasma leakage mechanisms triggered by RPA but not by bradykinin. PMID:10780980

Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markowitz, S.; Saito, K.; Moskowitz, M.A.

Utilizing /sup 125/I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated /sup 125/I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and /supmore » 125/I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of /sup 125/I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.« less

Management of amiodarone extravasation with intradermal hyaluronidase.

PubMed

Fox, Ashley N; Villanueva, Ruben; Miller, Jamie L

2017-10-01

The case of a patient who experienced extravasation while receiving amiodarone via a peripheral infusion and was treated with intradermal hyaluronidase is reported. A 60-year-old Caucasian man arrived at the emergency department after a motor vehicle collision. The patient was noted to have a subdural hematoma, multiple rib fractures, sternal body fracture, abdominal wall injury, left clavicle fracture, right humerus fracture, and vertebral fractures. His medical history included hypertension, atrial fibrillation, and stroke with residual right-sided weakness. On postoperative day 1, the patient developed atrial fibrillation and was started on i.v. amiodarone. Treatment resulted in conversion to sinus rhythm, but the patient again developed atrial fibrillation on postoperative day 5. During the morning hours of postoperative day 6, the patient experienced a peripheral i.v. line extravasation of amiodarone in his left arm. The amiodarone drip was discontinued, and amiodarone 400 mg orally twice daily was started. The nursing staff was instructed to treat the patient for the amiodarone extravasation with traditional nonpharmacologic measures, including warm compresses and elevation of the extremity. After extravasation, the patient reported severe pain at the site. Due to the patient's continued complaints of pain and the expanding area of induration, the interdisciplinary team elected to proceed with intradermal hyaluronidase. The patient reported significantly decreased pain and was discharged to inpatient rehabilitation on postoperative day 10 without any significant adverse effects. Administration of intradermal hyaluronidase after amiodarone extravasation was associated with decreased expansion of erythema and warmth as well as an improvement in patient-reported pain scores without any noted adverse effects. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Lesions Associated With Calcium Gluconate Extravasation: Presentation of 5 Clinical Cases and Analysis of Cases Published.

PubMed

Pacheco Compaña, Francisco Javier; Midón Míguez, José; de Toro Santos, Francisco Javier

2017-11-01

Calcium gluconate extravasation is a process, which, while not common, occurs more frequently in neonatal intensive care units. The aim of this study is to present a number of cases of calcium gluconate extravasation, which have occurred in our hospital, and to carry out a review of those clinical cases published in the literature to obtain relevant epidemiological data. Data were gathered on the medical histories of 5 patients who presented lesions secondary to calcium gluconate extravasation in our center. A review of the literature was also performed to include clinical cases of calcium gluconate extravasation already published. Data were collected on 60 cases published in 37 articles. Most patients (55%) were neonates. The average age of these neonates was 8 days. The commonest location of injuries was the back of the hand and wrist (42%). The 2 most frequent symptoms were the appearance of erythema (65%) and swelling/edema (48%) followed by the appearance of skin necrosis (47%), indurated skin (33%), and yellow-white plaques or papules (33%). Most cases are cured within a period of 3 to 6 months. Fifty percent of patients required surgery, and in 13% of cases, skin grafts were performed. The most frequent histological finding was the presence of calcium deposits. Other histological findings described were the presence of necrosis, lymphohistiocytic infíltrate, and granulomas. Most histological findings were located in the dermis. Most x-rays showing calcium deposits had been performed at 3 to 4 weeks. Calcium gluconate extravasation is a process, which, although infrequent, is associated with serious skin and soft-tissue lesions, mainly affecting infants. Further studies are needed to determine possible specific procedures to be carried out in these cases.

Online open-tubular fractionation scheme coupled with push-pull perfusion sampling for profiling extravasation of gold nanoparticles in a mouse tumor model.

PubMed

Su, Cheng-Kuan; Tseng, Po-Jen; Lin, Meng-Han; Chiu, Hsien-Ting; del Vall, Andrea; Huang, Yu-Fen; Sun, Yuh-Chang

2015-07-10

The extravasation of administered nano-drug carriers is a critical process for determining their distributions in target and non-target organs, as well as their pharmaceutical efficacies and side effects. To evaluate the extravasation behavior of gold nanoparticles (AuNPs), currently the most popular drug delivery system, in a mouse tumor model, in this study we employed push-pull perfusion (PPP) as a means of continuously sampling tumor extracellular AuNPs. To facilitate quantification of the extravasated AuNPs through inductively coupled plasma mass spectrometry, we also developed a novel online open-tubular fractionation scheme to allow interference-free determination of the sampled extracellular AuNPs from the coexisting biological matrix. After optimizing the flow-through volume and flow rate of this proposed fractionation scheme, we found that (i) the system's temporal resolution was 7.5h(-1), (ii) the stability presented by the coefficient of variation was less than 10% (6-h continuous measurement), and (iii) the detection limits for the administered AuNPs were in the range 0.057-0.068μgL(-1). Following an intravenous dosage of AuNPs (0.3mgkg(-1) body weight), in vivo acquired profiles indicated that the pegylated AuNPs (PEG-AuNPs) had greater tendency toward extravasating into the tumor extracellular space. We also observed that the accumulation of nanoparticles in the whole tumor tissues was higher for PEG-AuNPs than for non-pegylated ones. Overall, pegylation appears to promote the extravasation and accumulation of AuNPs for nano-drug delivery applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Simultaneous measurement of liposome extravasation and content release in tumors.

PubMed

Wu, N Z; Braun, R D; Gaber, M H; Lin, G M; Ong, E T; Shan, S; Papahadjopoulos, D; Dewhirst, M W

1997-03-01

The success of liposome-based drug delivery systems for tumor targeting relies on maximum extravasation of liposomes into tumor interstitium, as well as optimal release of contents from the liposomes once within the tumor Liposome extravasation and content release are two separate processes that can be individually or jointly manipulated so a method is needed to monitor these two processes independently and simultaneously. In this report, we describe a method to measure liposome extravasation and content release in tumor tissues growing in a rat skinfold window chamber preparation. Mixtures of liposomes containing either doxorubicin or calcein, both of which are fluorescent, and liposomes surface-labeled with rhodamine were injected intravenously. Fluorescent, light intensities in a tumor region in two fluorescent channels were measured using an image-processing system. Light intensities of plasma from blood samples were also measured using this system. These measurements were used to calculate the amounts of liposomes and released contents in both plasma and tumor interstitium. The calculations were based on the fact that the liposome surface labels and contents emit fluorescent light at different wavelengths and when encapsulated, the contents fluorescence is self-quenched. The model included equations to account for fluorescent light "cross-contamination" by the two fluorochromes as well as equations relating the measured fluorescent light intensities to the amounts of liposomes and released contents. This method was applied to three situations in which liposome extravasation and content release were manipulated in different, predictable ways. Our results indicate that this method can perform simultaneous independent and quantitative measurements of liposome extravasation and content release. This method can potentially be used to study drug delivery of other carrier systems in vivo.

Management of extravasation injuries: a retrospective study.

PubMed

Fırat, Cemal; Erbatur, Serkan; Aytekin, Ahmet Hamdi

2013-02-01

The extravasation of many agents during administration by way of the peripheral veins can produce severe necrosis of the skin and subcutaneous tissue. The incidence of an extravasation injury is elevated in the populations prone to complications, including the younger age groups. The severity of the necrosis depends on properties of the extravasated agent (vinca alkaloids, antracyclines, catecholamines, cationic solutions, osmotically active chemicals) including the type, concentration, and the quantity injected. In general, the primary diseases were chronic diseases such as hepatic or ischaemic encephalopathies, cardiac or pulmonary diseases, diabetes mellitus, and oncological diseases. The aim of this article was to explore the prevention, diagnosis, and treatment of extravasation injuries with a review of the literature. From January 2009 to August 2011, 22 patients were reviewed. Ten patients were children, and the others were adults. The surgical interventions were delayed until the development of the necrosis. A topical boric acid 3% solution was applied to all wounds with repetitive debridement. Debridement was performed once every 2 days and was continued until healthy tissue was obtained. The wounds of eight patients were repaired with split-thickness skin grafts, the wounds of six patients were reconstructed with randomised fasciocutaneous flaps, and the wounds of five patients healed by secondary intention. The wounds of three patients with massive swelling of the forearms were treated with only conservative modalities and limb elevation for 24-48 hours. Boric acid was found to promote granulation tissue in the wounds. The extravasation injuries can be prevented by using appropriate measures, such as the avoidance of perfusion under pressure, patient participation in pain follow-up, wound management by experienced health professionals, and preference for large and suitable veins.

Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism.

PubMed

de Garavilla, L; Vergnolle, N; Young, S H; Ennes, H; Steinhoff, M; Ossovskaya, V S; D'Andrea, M R; Mayer, E A; Wallace, J L; Hollenberg, M D; Andrade-Gordon, P; Bunnett, N W

2001-08-01

Thrombin, generated in the circulation during injury, cleaves proteinase-activated receptor 1 (PAR1) to stimulate plasma extravasation and granulocyte infiltration. However, the mechanism of thrombin-induced inflammation in intact tissues is unknown. We hypothesized that thrombin cleaves PAR1 on sensory nerves to release substance P (SP), which interacts with the neurokinin 1 receptor (NK1R) on endothelial cells to cause plasma extravasation. PAR1 was detected in small diameter neurons known to contain SP in rat dorsal root ganglia by immunohistochemistry and in situ hybridization. Thrombin and the PAR1 agonist TFLLR-NH(2) (TF-NH(2)) increased [Ca(2+)](i) >50% of cultured neurons (EC(50)s 24 mu ml(-1) and 1.9 microM, respectively), assessed using Fura-2 AM. The PAR1 agonist completely desensitized responses to thrombin, indicating that thrombin stimulates neurons through PAR1. Injection of TF-NH(2) into the rat paw stimulated a marked and sustained oedema. An NK1R antagonist and ablation of sensory nerves with capsaicin inhibited oedema by 44% at 1 h and completely by 5 h. In wild-type but not PAR1(-/-) mice, TF-NH(2) stimulated Evans blue extravasation in the bladder, oesophagus, stomach, intestine and pancreas by 2 - 8 fold. Extravasation in the bladder, oesophagus and stomach was abolished by an NK1R antagonist. Thus, thrombin cleaves PAR1 on primary spinal afferent neurons to release SP, which activates the NK1R on endothelial cells to stimulate gap formation, extravasation of plasma proteins, and oedema. In intact tissues, neurogenic mechanisms are predominantly responsible for PAR1-induced oedema.

Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats. Comparison of lateral fluid percussion and cortical impact models.

PubMed

Hicks, R R; Baldwin, S A; Scheff, S W

1997-01-01

Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical techniques for alterations in the serum protein, IgG, and the cytoskeletal protein, microtubule-associated protein 2 (MAP2). Both models induced profound alterations in these proteins in the ipsilateral cortex and hippocampus compared to sham-injured controls. Following an injury of moderate severity, the CI injury resulted in greater IgG extravasation in the cortex and hippocampus than the FP injury. Conversely, after a mild injury, IgG extravasation in the hippocampus was greater for FP than CI. All of the animals in the CI group and most of the FP group showed a loss of MAP2 in the hippocampus. The specific subregions within the cortex and hippocampus that were affected by the injury varied between models, despite having identical impact sites. These data demonstrate that there are both similarities and differences between a CI and FP injury on vascular and neuronal cystoskeletal integrity, which should be considered when utilizing these animal models to study selected features of human head injury.

Surgical treatment of ulcers caused by extravasation of cytotoxic drugs.

PubMed

D'Andrea, Francesco; Onesti, Maria Giuseppina; Nicoletti, Giovanni Francesco; Grella, Elisa; Renzi, Luca Francesco; Spalvieri, Cristina; Scuderi, Nicolò

2004-01-01

Despite preventive measures, the extravasation of cytotoxic drugs still occurs in 0.6% to 6% of cases. The aetiology is thought to be that tissue necrosis develops into a chronic ulcer, which causes problems if the harmful action of the drug is not blocked. From 1988-2002 at the Department of Plastic Surgery of Rome University "La Sapienza", 240 patients presented with extravasation of cytotoxic drugs; all had been treated with an original conservative protocol first described in 1994, based on the repeated local infiltration of a large quantity of saline solution (90-540 ml) into the area of extravasation. We considered only cases with actively necrotic lesions. Eleven of the 240 patients (5%) had ulcers ranging from small ulcers to extensive areas of tissue necrosis. Of the 11 patients, eight had already had ulcers, while the remaining three were those in whom our conservative protocol had not prevented necrosis. They were all operated on and given grafts, local flaps, reverse radial flaps, and free flaps.

Subpial Hematoma and Extravasation in the Interhemispheric Fissure with Subarachnoid Hemorrhage

PubMed Central

Matsuoka, Go; Abe, Kayoko; Okada, Yoshikazu; Sakai, Shuji

2015-01-01

A recent report on computed tomography (CT) findings of contrast extravasation in subarachnoid hemorrhage (SAH) with Sylvian hematoma suggests that the occurrence of the hematoma is secondary to bleeding in the subpial space. Our patient was in his sixties and was admitted to the hospital because of loss of consciousness (Glasgow Coma Scale E4V1M4). SAH was diagnosed in plain head CT, and growing hematomas were observed in the Sylvian and interhemispheric fissures following a subarachnoid hemorrhage. CT angiography (CTA) using a dual-phase scan protocol revealed contrast extravasation in both the fissures in the latter phase, and hematoma in the interhemispheric fissure contained multiple bleeding points. This case indicates that the occurrence of subpial hematoma such as Sylvian hematoma can be a secondary event following subpial bleeding from damaged small vessels elsewhere in the cranium. Instead of four-dimensional (4D) CT, the dual-phase CTA technique may help detect minor extravasations with usual helical CT scanner. PMID:25963159

[Emergency management of extravasation in children].

PubMed

Pasquesoone, L; Aljudaibi, N; Ellart, J; Guerreschi, P; Duquennoy-Martinot, V

2016-10-01

The subcutaneous diffusion of intravenous drips, or extravasation, is a frequent iatrogenic complication in children, mainly in the neonatal period. This potentially severe pathology can lead to local ischemia that sometimes mimics compartment syndrome. It can also evolve towards vast soft-tissue necrosis. Nursing staff often underestimate the risk of functional, aesthetic, and psychological consequences. The speed and quality of the initial medical and surgical management can greatly decrease morbidity associated with extravasation. Prevention is fundamental, such as raising awareness in and training medical and paramedical staffs and creating efficient protocols. Surgical management involving aspiration and washing the site as early as possible improves the prognosis. Aspiration and washing can be done on a larger area if one criteria of severity is met, particularly in cases of extravasation using a vesicant or hyperosmolar agent. If necrotic lesions appear, it is wise to wait until they become delimited. Debridement and coverage can be performed using classical methods. Copyright © 2016. Published by Elsevier Masson SAS.

Ultrasound-guided shoulder MR arthrography: comparison of rotator interval and posterior approach.

PubMed

Ogul, Hayri; Bayraktutan, Ummugulsum; Ozgokce, Mesut; Tuncer, Kutsi; Yuce, Ihsan; Yalcin, Ahmet; Pirimoglu, Berhan; Sagsoz, Erdem; Kantarci, Mecit

2014-01-01

The purpose of this study was to prospectively evaluate the two different ultrasound-guided injection techniques for magnetic resonance (MR) arthrography of the shoulder. This study included 100 patients [50 rotator interval group (n=50) vs. 50 posterior approach group (n=50)]. All procedures were performed by the same radiologist. The two injection techniques were compared. The discomfort during and after arthrography was evaluated. Extraarticular contrast media extravasation was graded according to the MRI findings. The number of injection attempts, effect of contrast media extravasation rate on diagnostic quality and procedure times were recorded. There were no significant difference between the posterior and rotator interval puncture groups with regard to pain (P=.915), procedure times (P=.401) or attempt scores (P=.182). There were significantly more contrast media extravasations with rotator interval approach than posterior approach (P<.05). Both techniques were successful and well tolerated by patients. Posterior injection technique provided a more effective route with decreased extravasation rate and easier approach compared to the rotator interval approach. © 2014.

Extravasation mucocele involving the ventral surface of the tongue (glands of Blandin-Nuhn).

PubMed

Guimarães, M S; Hebling, J; Filho, V A P; Santos, L L; Vita, T M; Costa, C A S

2006-11-01

Mucocele is a lesion that involves the salivary glands and respective current ducts caused mainly by traumas in the affected area. Two different histological forms can be found: extravasation phenomenon and mucus-retention cyst where the former is the most frequently observed involving minor salivary glands such as the glands present in the anterior portion of the ventral surface of the tongue (glands of Blandin-Nuhn). This report describes a large lesion involving the ventral surface of the tongue that was definitively diagnosed by histological examination as extravasation mucocele. Important concepts are reviewed to help clinicians correctly diagnose and treat this pathology.

A successful combined treatment with dermal substitutes and products of regenerative medicine in a patient affected by extravasation injury from hypertonic solution.

PubMed

Onesti, Maria Giuseppina; Carella, Sara; Maruccia, Michele; Marchese, Cinzia; Fino, Pasquale; Scuderi, Nicolò

2012-01-01

In neonatal intensive care units, extravasation is one of the most common injuries occurring in infants as a complication of infusion therapy. These very preterm infants have immature skin which is easily damaged. They often require a longer duration of intravenous therapy, and obtaining intravenous access can be difficult. An invasive treatment should be avoided, whenever possible, particularly for very immature infants. In our Special Operative Unit for ulcers and difficult-to-heal wounds, University of Rome, we successfully treated a premature neonate, who experienced extravasation of hypertonic fluid, using dermal substitutes and products of regenerative medicine.

Cavitational kyphoplasty: a new technique for reducing the rates of cement extravasation through targeted low-pressure cement injection.

PubMed

Mattei, Tobias A

2017-06-01

Previous studies have demonstrated lower rates of cement extravasation when comparing balloon kyphoplasty with vertebroplasty, an effect attributed to the low-pressure injection. However, in patients with isolated endplate fractures, balloon kyphoplasty may lead to further endplate damage and increased risks of intradiscal extravasation. The author provides a stepwise description of a new technique called cavitational kyphoplasty that allows targeted low-pressure cement injection without the necessity of balloon inflation. The new technique of cavitational kyphoplasty has been shown to be specially useful in patients with isolated endplate fractures without significant loss of the vertebral body height.

Contrast Media Extravasation of Computed Tomography and Magnetic Resonance Imaging: Management Guidelines for the Radiologist.

PubMed

Nicola, Refky; Shaqdan, Khalid Wael; Aran, Shima; Prabhakar, Anand M; Singh, Ajay Kumar; Abujudeh, Hani H

2016-01-01

Intravenous contrast administration has been of great importance in diagnostic radiology, but it is not without risks either due to the local, systemic allergic reactions or due to subcutaneous extravasation of contrast media. Subcutaneous contrast medium extravasationis an infrequent, yet a well-recognized complication. However, most incidents are minor and can be managed conservatively, but there are a few cases that require immediate surgical intervention. This article discusses the risks factors, clinical manifestations, and conservative and surgical approaches of subcutaneous contrast media extravasation for both computed tomography and magnetic resonance imaging. Copyright © 2015 Mosby, Inc. All rights reserved.

Thermosensitive liposomes: extravasation and release of contents in tumor microvascular networks.

PubMed

Gaber, M H; Wu, N Z; Hong, K; Huang, S K; Dewhirst, M W; Papahadjopoulos, D

1996-12-01

The purpose of this study was to determine whether hyperthermic exposure would accelerate drug release from thermosensitive sterically stabilized liposomes and enhance their extravasation in tumor tissues. In vivo fluorescence video microscopy was used to measure the extravasation of liposomes, as well as release of their contents, in a rat skin flap window chamber containing a vascularized mammary adenocarcinoma under defined thermal conditions (34 degrees, 42 degrees, and 45 degrees C). Images of tissue areas containing multiple blood vessels were recorded via a SIT camera immediately before, and for up to 2 h after i.v. injection of two liposome populations with identical lipid composition: one liposome preparation was surface labeled with Rhodamine-PE (Rh-PE) and the other contained either Doxorubicin (Dox) or calcein at self-quenching concentrations. The light intensity of the entire tissue area was measured at 34 degrees C (the physiological temperature of the skin) for 1 h, and at 42 degrees or 45 degrees C for a second hour. These measurements were then used to calculate the fluorescent light intensity arising from each tracer (liposome surface label and the released contents) inside the vessel and in the interstitial region. The calculated intensity of Rh-PE for the thermosensitive liposomes in the interstitial space (which represents the amount of extravasated liposomes) was low during the first hour, while temperature was maintained at 34 degrees C and increased to 47 times its level before heating, when the tumor was heated at 42 degrees or 45 degrees C for 1 h. The calculated intensity of the liposome contents (Dox) in the interstitial space was negligible at 34 degrees C, and increased by 38- and 76-fold, when the tumor was heated at 42 degrees and 45 degrees C for 1 h, respectively. Similar values were obtained when calcein was encapsulated in liposomes instead of Dox. A similar increase in liposome extravasation was seen with nonthermosensitive liposomes, but negligible release of Dox occurred when the window chamber was heated to 45 degrees C for 1 h. Extravasation of liposomes continued after heating was stopped, but content release stopped after removal of heat. Release of Dox from extravasated liposomes was also seen if heating was applied 24 h after liposome administration, but no further enhancement of liposome extravasation occurred in this case. Our data suggest that hyperthermia can be used to selectively enhance both the delivery and the rate of release of drugs from thermosensitive liposomes to targeted tissues.

A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters.

PubMed

Loubani, Osama M; Green, Robert S

2015-06-01

The aim of this study was to collect and describe all published reports of local tissue injury or extravasation from vasopressor administration via either peripheral intravenous (IV) or central venous catheter. A systematic search of Medline, Embase, and Cochrane databases was performed from inception through January 2014 for reports of adults who received vasopressor intravenously via peripheral IV or central venous catheter for a therapeutic purpose. We included primary studies or case reports of vasopressor administration that resulted in local tissue injury or extravasation of vasopressor solution. Eighty-five articles with 270 patients met all inclusion criteria. A total of 325 separate local tissue injury and extravasation events were identified, with 318 events resulting from peripheral vasopressor administration and 7 events resulting from central administration. There were 204 local tissue injury events from peripheral administration of vasopressors, with an average duration of infusion of 55.9 hours (±68.1), median time of 24 hours, and range of 0.08 to 528 hours. In most of these events (174/204, 85.3%), the infusion site was located distal to the antecubital or popliteal fossae. Published data on tissue injury or extravasation from vasopressor administration via peripheral IVs are derived mainly from case reports. Further study is warranted to clarify the safety of vasopressor administration via peripheral IVs. Copyright © 2015 Elsevier Inc. All rights reserved.

T1- and T2*-dominant extravasation correction in DSC-MRI: Part I—theoretical considerations and implications for assessment of tumor hemodynamic properties

PubMed Central

Bjornerud, Atle; Sorensen, A Gregory; Mouridsen, Kim; Emblem, Kyrre E

2011-01-01

We present a novel contrast agent (CA) extravasation-correction method based on analysis of the tissue residue function for assessment of multiple hemodynamic parameters. The method enables semiquantitative determination of the transfer constant and can be used to distinguish between T1- and T2*-dominant extravasation effects, while being insensitive to variations in tissue mean transit time (MTT). Results in 101 patients with confirmed glioma suggest that leakage-corrected absolute cerebral blood volume (CBV) values obtained with the proposed method provide improved overall survival prediction compared with normalized CBV values combined with an established leakage-correction method. Using a standard gradient-echo echo-planar imaging sequence, ∼60% and 10% of tumors with detectable CA extravasation mainly exhibited T1- and T2*-dominant leakage effects, respectively. The remaining 30% of leaky tumors had mixed T1- and T2*-dominant effects. Using an MTT-sensitive correction method, our results show that CBV is underestimated when tumor MTT is significantly longer than MTT in the reference tissue. Furthermore, results from our simulations suggest that the relative contribution of T1- versus T2*-dominant extravasation effects is strongly dependent on the effective transverse relaxivity in the extravascular space and may thus be a potential marker for cellular integrity and tissue structure. PMID:21505483

Fluid extravasation during hip arthroscopy.

PubMed

Stafford, Giles H; Malviya, Ajay; Villar, Richard N

2011-01-01

The amount of fluid that may be lost into the soft tissues during hip arthroscopic surgery is unknown. We measured the volumes of irrigation fluid infused, operating time, fluid pressures and volumes of fluid recovered in 36 therapeutic hip arthroscopies. We excluded those where fluid was lost to the floor, leaving 28 patients. The majority were undergoing surgery for the treatment of femoroacetabular impingement. In 5 patients an intra-articular contrast medium was instilled, in order to establish the likely location of any extravasated fluid. The mean operating time was 68 minutes (31 to 120), and the mean infusion pressure was 46 mm Hg (30 to 70). The mean volume of infused fluid was 9677 ml (95% confidence interval (CI) 7715 to 11638) and the mean volume of fluid recovered was 8544 ml (95% CI 6715 to 10373). The mean fluid extravasation loss into the peri-articular tissues was 1132 ml (95% CI 808 ml to 1456 ml). There was a significant correlation between the volume of extravasated fluid and both the length of operation and the volume of infused fluid used. We had no adverse events in our series. During arthroscopic hip surgery more than a litre of irrigation fluid may be extravasated into the soft tissues. In order to reduce problems related to this we attempt to keep operating times low, and maintain intra-operative fluid pressures as low as possible.

Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.

PubMed

Mouridsen, H T; Langer, S W; Buter, J; Eidtmann, H; Rosti, G; de Wit, M; Knoblauch, P; Rasmussen, A; Dahlstrøm, K; Jensen, P B; Giaccone, G

2007-03-01

The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months. In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site. Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).

Computed tomography analysis of third webspace injections for interdigital neuroma.

PubMed

Hembree, W Chad; Groth, Adam T; Schon, Lew C; Guyton, Gregory P

2013-04-01

Injection for interdigital neuroma (IDN) may not selectively target the common digital nerve. We investigated the anatomical localization and extent of extravasation with injection for IDN. Two fellowship-trained foot and ankle surgeons injected radiopaque contrast into the third webspace of 49 cadaveric specimens (29 with 2 mL and 20 with 1 mL). Computed tomography scan of each specimen was obtained. An independent blinded foot and ankle surgeon analyzed the scans. All injections were accurate. Contrast was found in the second (greater than 70%) and fourth (greater than 30%) webspaces in both injection volume groups. No contrast was found within the third metatarsophalangeal joint. Extravasation extent was significantly greater with 2 mL versus 1 mL of solution in the medial to lateral (27.9 [7.8] mm vs 23.7 [6.0] mm; P = .05) and distal to proximal (52.1 [13.7] mm vs 40.4 [16.1] mm; P = .01) planes. No differences were observed in extravasation extent between surgeons. Injection for IDN was accurate, and extravasation extended into adjacent webspaces in a large percentage of specimens with both solution volumes. Lower extent of extravasation with 1 mL of solution did not indicate better selectivity of injection. Steroid injections for interdigital neuroma were accurate for therapeutic purposes but not diagnostic, except potentially for distinguishing webspace pain from joint pain.

Deep dopamine extravasation injury: a case report.

PubMed

Phillips, Reid A; Andrades, Patricio; Grant, John H; Ray, Peter D

2009-07-01

We report the case of a 3-month-old girl with Down's syndrome, who sustained a deep and massive extravasation of dopamine, resulting in segmented, full-thickness skin necrosis and transient brachial plexus palsy of her left upper extremity. The patient was managed conservatively, including wound care, de-bridement of necrotic tissue, secondary wound healing and intensive physical therapy. The patient showed a satisfactory outcome with complete secondary closure of her wounds and full brachial plexus recovery after 1 year of follow-up. The mechanism of action of dopamine in the deep soft tissue, the difficulties of an adequate diagnosis of a deep dopamine extravasation and alternative treatments are presented in this article.

5-fluorouracil extravasation following port failure.

PubMed

Nesti, S P; Kovac, R

2000-01-01

A case is presented of cytotoxic extravasation as a result of an implantable venous port being perforated by a standard Huber needle. A patient receiving 5-fluorouracil via a dual reservoir port, implanted within the left chest wall, presented with hemoserous discharge from the right needle entry site. The left chest wall was warm to touch, erythematous, and swollen. Subcutaneous infiltration was suspected, and the infusion was ceased. A venogram was performed demonstrating significant extravasation around the left reservoir only. On port removal, inspection showed the Huber needle had penetrated the base plate on the left side. It is recommended that this complication be added as a possible sequelae of central venous port use.

PERIVASCULAR EXTRAVASATION OF THORIUM DIOXIDE PREPARATION. TWENTY-ONE-YEAR FOLLOW-UP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Germon, P.; Howard, J.M.; James, P.M.

The course of a patient is described with a 21-yr followup after the extravasation of ThO/sub 2/ preparation (Thorotrast) into the soft tissue of the arm. The resultant concentration of the Th in the spleen led repeatedly to the erroneous radiographic iuterpretation of splenic calcification. (auth)

Dynamic-contrast-enhanced-MRI with extravasating contrast reagent: Rat cerebral glioma blood volume determination

NASA Astrophysics Data System (ADS)

Li, Xin; Rooney, William D.; Várallyay, Csanád G.; Gahramanov, Seymur; Muldoon, Leslie L.; Goodman, James A.; Tagge, Ian J.; Selzer, Audrey H.; Pike, Martin M.; Neuwelt, Edward A.; Springer, Charles S.

2010-10-01

The accurate mapping of the tumor blood volume (TBV) fraction ( vb) is a highly desired imaging biometric goal. It is commonly thought that achieving this is difficult, if not impossible, when small molecule contrast reagents (CRs) are used for the T1-weighted (Dynamic-Contrast-Enhanced) DCE-MRI technique. This is because angiogenic malignant tumor vessels allow facile CR extravasation. Here, a three-site equilibrium water exchange model is applied to DCE-MRI data from the cerebrally-implanted rat brain U87 glioma, a tumor exhibiting rapid CR extravasation. Analyses of segments of the (and the entire) DCE data time-course with this "shutter-speed" pharmacokinetic model, which admits finite water exchange kinetics, allow TBV estimation from the first-pass segment. Pairwise parameter determinances were tested with grid searches of 2D parametric error surfaces. Tumor blood volume ( vb), as well as ve (the extracellular, extravascular space volume fraction), and Ktrans (a CR extravasation rate measure) parametric maps are presented. The role of the Patlak Plot in DCE-MRI is also considered.

Effect of quercetin on plasma extravasation in rat CNS and dura mater by ACE and NEP inhibition.

PubMed

Cyrino, Luiz A R; Cardoso, Ronie C F; Hackl, Luciane P N; Nicolau, Mauro

2002-09-01

The effects of quercetin on substance P-induced plasma protein extravasation (PE) in the rat dura mater, cerebellum, olfactory bulb and cortex and also its modulation by endopeptidases, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) were studied. PE was assessed by photometric measurement of extravasated Evans blue. Substance P (SP) and NEP or ACE inhibitors increased the PE in dura mater. Pretreatment with captopril or phosphoramidon potentiated PE induced by SP in the dura mater and cerebellum, respectively. Quercetin increased the PE in the dura mater, cerebellum and cortex. Further results suggested that the PE induced by SP in the dura mater was enhanced by pretreatment with quercetin, similar to that observed with selective peptidase inhibitors. Quercetin-stimulated extravasation in all tissues was abolished by NK-1 receptor blockade. These results suggest that quercetin increases PE in the dura mater and CNS tissues by inhibiting NEP and/or ACE, showing that the effect induced in the dura mater, cerebellum and cortex occurs through endogenous SP accumulation. Copyright 2002 John Wiley & Sons, Ltd.

The CD44-initiated pathway of T-cell extravasation uses VLA-4 but not LFA-1 for firm adhesion

PubMed Central

Siegelman, Mark H.; Stanescu, Diana; Estess, Pila

2000-01-01

Leukocytes extravasate from the blood in response to physiologic or pathologic demands by means of complementary ligand interactions between leukocytes and endothelial cells. The multistep model of leukocyte extravasation involves an initial transient interaction (“rolling” adhesion), followed by secondary (firm) adhesion. We recently showed that binding of CD44 on activated T lymphocytes to endothelial hyaluronan (HA) mediates a primary adhesive interaction under shear stress, permitting extravasation at sites of inflammation. The mechanism for subsequent firm adhesion has not been elucidated. Here we demonstrate that the integrin VLA-4 is used in secondary adhesion after CD44-mediated primary adhesion of human and mouse T cells in vitro, and by mouse T cells in an in vivo model. We show that clonal cell lines and polyclonally activated normal T cells roll under physiologic shear forces on hyaluronate and require VCAM-1, but not ICAM-1, as ligand for subsequent firm adhesion. This firm adhesion is also VLA-4 dependent, as shown by antibody inhibition. Moreover, in vivo short-term homing experiments in a model dependent on CD44 and HA demonstrate that superantigen-activated T cells require VLA-4, but not LFA-1, for entry into an inflamed peritoneal site. Thus, extravasation of activated T cells initiated by CD44 binding to HA depends upon VLA-4–mediated firm adhesion, which may explain the frequent association of these adhesion receptors with diverse chronic inflammatory processes. PMID:10712440

The impact of bladder neck mucosal eversion during open radical prostatectomy on bladder neck stricture and urinary extravasation.

PubMed

Schoeppler, Gita M; Zaak, Dirk; Clevert, Dirk-Andre; Schuhmann, Petra; Reich, Oliver; Seitz, Michael; Khoder, Wael Y; Staehler, Michael; Stief, Christian G; Buchner, Alexander

2012-10-01

To determine whether the bladder neck mucosal eversion (BNM-eversion) during radical retropubic prostatectomy (RRP) reduces the risk of bladder neck stricture (BNS) and of peri-anastomotic extravasation (PAE) in postoperative cystography. Two hundred and eleven patients with clinically localized prostate cancer underwent RRP and were prospectively randomized into patients with BNM-eversion (group I) and without BNM-eversion (group II). All patients underwent an evaluation of PAE by retrograde cystography on postoperative day 8. We assessed BNS after 6 months. Ninety-two patients with and 113 patients without BNM-eversion were included. There was no significant difference in baseline characteristics, including age, TNM-classification, Gleason score, PSA, prostate volume, and blood loss in both groups. A complete follow-up of 6 months for BNS was available for 188 patients (89.1 %). Sixteen BNS out of 188 patients were recorded, 4.7 % (n = 4) in group I and 11.7 % (n = 12) in group II (p = 0.09). Data from 205 out of 211 patients were available for the evaluation of the extravasation by cystography. Peri-anastomotic extravasation was detectable in 11.96 %, (11/205) in group I and in 21.24 % (24/205) in group II (p = 0.08). BNM-eversion does not have a positive influence on the prevention of bladder neck strictures. Peri-anastomotic extravasation detected by cystography does not correlate with a formation of bladder neck stricture.

Protection against vascular leak in neprilysin transgenic mice with complex overexpression pattern.

PubMed

Wick, Marilee J; Loomis, Zoe L; Harral, Julie W; Le, Mysan; Wehling, Carol A; Miller, York E; Dempsey, Edward C

2016-12-01

Neprilysin (NEP) is a cell surface metallopeptidase found in many tissues. Based mostly on pharmacological manipulations, NEP has been thought to protect blood vessels from plasma extravasation. We have suggested that NEP may protect against pulmonary vascular injury. However, these prior studies did not utilize mice which overexpress NEP. The aims of the present investigation were to develop and characterize doubly transgenic (DT) mice that overexpress NEP universally and conditionally, and to investigate the protective effect that overexpressed NEP may have against plasma extravasation in the vasculature. The duodenum, which is often used to assess vascular permeability, and in which the NEP protein was overexpressed in our DT mice two-fold, was selected as our experimental preparation. We found that substance P-induced plasma extravasation was decreased substantially (3.5-fold) in the duodenums of our doxycycline-treated DT mice, giving independent evidence of NEP's protective effects against plasma extravasation. Transgenic lung NEP protein was not stably expressed in the DT mice, so we were not able to test the effect of NEP overexpression in the lung. Although initially overexpressed nearly nine-fold at that site, pulmonary NEP protein overexpression eventually dissipated. Surprisingly, at a time when there was no lung transgenic NEP protein overexpression, lung NEP mRNA expression was still increased 23-fold, indicating that the expression defect probably is not transcriptional. These studies help to characterize our complex transgenic model of NEP overexpression and further demonstrate NEP's protective effects against plasma extravasation.

Endothelial-Mesenchymal Transition of Brain Endothelial Cells: Possible Role during Metastatic Extravasation

PubMed Central

Krizbai, István A.; Gasparics, Ákos; Nagyőszi, Péter; Fazakas, Csilla; Molnár, Judit; Wilhelm, Imola; Bencs, Rita; Rosivall, László; Sebe, Attila

2015-01-01

Cancer progression towards metastasis follows a defined sequence of events described as the metastatic cascade. For extravasation and transendothelial migration metastatic cells interact first with endothelial cells. Yet the role of endothelial cells during the process of metastasis formation and extravasation is still unclear, and the interaction between metastatic and endothelial cells during transendothelial migration is poorly understood. Since tumor cells are well known to express TGF-β, and the compact endothelial layer undergoes a series of changes during metastatic extravasation (cell contact disruption, cytoskeletal reorganization, enhanced contractility), we hypothesized that an EndMT may be necessary for metastatic extravasation. We demonstrate that primary cultured rat brain endothelial cells (BEC) undergo EndMT upon TGF-β1 treatment, characterized by the loss of tight and adherens junction proteins, expression of fibronectin, β1-integrin, calponin and α-smooth muscle actin (SMA). B16/F10 cell line conditioned and activated medium (ACM) had similar effects: claudin-5 down-regulation, fibronectin and SMA expression. Inhibition of TGF-β signaling during B16/F10 ACM stimulation using SB-431542 maintained claudin-5 levels and mitigated fibronectin and SMA expression. B16/F10 ACM stimulation of BECs led to phosphorylation of Smad2 and Smad3. SB-431542 prevented SMA up-regulation upon stimulation of BECs with A2058, MCF-7 and MDA-MB231 ACM as well. Moreover, B16/F10 ACM caused a reduction in transendothelial electrical resistance, enhanced the number of melanoma cells adhering to and transmigrating through the endothelial layer, in a TGF-β-dependent manner. These effects were not confined to BECs: HUVECs showed TGF-β-dependent SMA expression when stimulated with breast cancer cell line ACM. Our results indicate that an EndMT may be necessary for metastatic transendothelial migration, and this transition may be one of the potential mechanisms occurring during the complex phenomenon known as metastatic extravasation. PMID:25742314

Two proteins modulating transendothelial migration of leukocytes recognize novel carboxylated glycans on endothelial cells.

PubMed

Srikrishna, G; Panneerselvam, K; Westphal, V; Abraham, V; Varki, A; Freeze, H H

2001-04-01

We recently showed that a class of novel carboxylated N:-glycans was constitutively expressed on endothelial cells. Activated, but not resting, neutrophils expressed binding sites for the novel glycans. We also showed that a mAb against these novel glycans (mAbGB3.1) inhibited leukocyte extravasation in a murine model of peritoneal inflammation. To identify molecules that mediated these interactions, we isolated binding proteins from bovine lung by their differential affinity for carboxylated or neutralized glycans. Two leukocyte calcium-binding proteins that bound in a carboxylate-dependent manner were identified as S100A8 and annexin I. An intact N terminus of annexin I and heteromeric assembly of S100A8 with S100A9 (another member of the S100 family) appeared necessary for this interaction. A mAb to S100A9 blocked neutrophil binding to immobilized carboxylated glycans. Purified human S100A8/A9 complex and recombinant human annexin I showed carboxylate-dependent binding to immobilized bovine lung carboxylated glycans and recognized a subset of mannose-labeled endothelial glycoproteins immunoprecipitated by mAbGB3.1. Saturable binding of S100A8/A9 complex to endothelial cells was also blocked by mAbGB3.1. These results suggest that the carboxylated glycans play important roles in leukocyte trafficking by interacting with proteins known to modulate extravasation.

Extravasation injuries.

PubMed

Chiu, Kenneth; Tindholdt, Tyge Tind; Tønseth, Kim Alexander

2016-02-09

It is common for an intravascular catheter to be inserted to administer various types of therapy. Extravasation occurs frequently, and in the most severe cases plastic surgeons are often summoned to assess the extent of the injury and the possibility for reconstruction. The Department of Plastic and Reconstructive Surgery at Oslo University Hospital assesses approximately 15 severe cases of this type each year.

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2014-09-01

Staszewski, et al., The PHSCN dendrimer as a more potent inhibitor of human breast cancer cell invasion, extravasation, and lung colony formation...the PHSCN dendrimer as an inhibitor of human prostate cancer cell invasion, extravasation, and lung colony formation. Clin Exp Metastasis, 2010. 27(3

Identification of involved tissue during surgical treatment of doxorubicin-induced extravasation necrosis.

PubMed

Cohen, F J; Manganaro, J; Bezozo, R C

1983-01-01

The extravascular escape of intravenously administered doxorubicin (Adriamycin) leads to a painful, slowly enlarging subcutaneous lesion which, if not diagnosed, will progress to a chronic severe cellulitis with inflammatory reaction, ulceration of the skin, and possible further involvement. Past attempts at immediate treatment have failed because of, or have been complicated by, incomplete removal of the doxorubicin with continuing tissue necrosis. Three patients who underwent antineoplastic therapy with doxorubicin suffered extravasation leading to deep tissue necrosis requiring skin grafts. In all cases identification of doxorubicin-containing tissue was accomplished by injection of fluorescein. The residual necrotic tissue that did not fluoresce was removed. A protocol is presented to detect doxorubicin extravasation and distinguish the viable from the nonviable components.

Inhibition of tracheal vascular extravasation by liposome-encapsulated albuterol in rats.

PubMed

Zhang, W; Guo, L; Nadel, J A; Papahadjopoulos, D

1998-03-01

To develop a liposome-based system for systemic delivery of anti-inflammatory drugs to airways and other inflamed tissues. Postcapillary venular gap junctions open during airway inflammation and allow fluid accumulation and permit molecules (e.g. complement, kininogen) to enter tissues, initiating inflammatory cascades. Beta-adrenergic agonists prevent inflammatory plasma extravasation, but because of their deleterious side effects, they are not used intravenously. When sterically stabilized "stealth" liposomes are injected i.v., they remain in the circulation for long periods. Inflammatory mediators [e.g., substance P(SP)] open postcapillary venular gaps and allow liposomes and their contents to be deposited selectively in the inflamed tissue. We hypothesized that liposomes encapsulating a beta-adrenergic agonist, such as albuterol, would deposit selectively in inflamed airway tissue, where the drug would slowly leak out of the liposomes, resulting in closure of the gaps, thus preventing subsequent inflammatory extravasation. To test this hypothesis, we delivered albuterol-loaded liposomes i.v. in rats. Then we injected SP to open the venular gaps and allow accumulation of the drug-loaded liposomes in airway tissue. We examined whether this treatment resulted in inhibition of subsequent plasma extravasation induced by SP. The results indicate that liposome-encapsulated albuterol inhibits subsequent extravasation, presumably by leaking out of liposomes in airway tissue. This inhibition occurs for prolonged periods of time and with limited side effects compared to the effect of free albuterol. We conclude that liposomes loaded with appropriate drugs, by migrating to inflamed tissue and subsequently inhibiting inflammatory cascades, may be of therapeutic value in inflammatory diseases.

Severe Extravasation Injuries in Neonates: A Report of 34 Cases.

PubMed

Kostogloudis, Nikolaos; Demiri, Efterpi; Tsimponis, Antonios; Dionyssiou, Dimitrios; Ioannidis, Sotirios; Chatziioannidis, Ilias; Nikolaidis, Nikolaos

2015-01-01

Extravasation injuries are a common and challenging problem in hospitalized newborns. Accidental infusion leakage into the surrounding tissues in immature infants may frequently result in skin necrosis, with significant risk of functional and cosmetic impairment. In the present study we reviewed 34 cases of severe extravasation injuries occurring in 1,409 neonates hospitalized in a single neonatal unit over 24 months (incidence 2.4%). Total parenteral nutrition solutions were involved in most cases. All patients were treated within 30 minutes after the injury was recorded using a flush-out technique with normal saline irrigation and occlusive paraffin dressings of the infiltrated area. The majority of injuries affected preterm, low-birthweight infants (mean gestation 32 wks + 6 days, mean birth weight 1,885 g), with a mean age at the time of injury of 11.6 days and a mean weight of 2,045 g. Neither gestational age (p = 0.87) or birthweight significantly affected (p = 0.07) the incidence of extravasation injuries, although the incidence of skin necrosis had a significant correlation with gestational age (p = 0.009) and birthweight (p < 0.001). All patients responded well to treatment and their wounds healed uneventfully within a maximum of 25 days without the need for secondary surgery for skin coverage. Extravasation injuries in extremely preterm and low-birthweight infants are more likely to lead to skin necrosis. Peripheral venous catheterization should be performed with caution in these patients to prevent such injuries. Immediate irrigation with normal saline is recommended to reduce toxic sequelae in the infiltrated area. © 2015 Wiley Periodicals, Inc.

Introduction of vincristine mini-bags and an assessment of the subsequent risk of extravasation.

PubMed

Nurgat, Z A; Smythe, M; Al-Jedai, A; Ewing, S; Rasheed, W; Belgaumi, A; Ahmed, S O; Ashour, M; Al Agil, A; Siddiqui, K; Aljurf, M

2015-10-01

Numerous international organisations have advocated the preparation of vincristine in small volume intravenous bags in order to eliminate inadvertent intrathecal administration. However, the risk of extravasation is a significant deterrent, and adoption of this practice has been variable and only hesitantly accepted in the clinical setting. We carried out a study with the aims of establishing the incidence of reported extravasation of vincristine administration to paediatric and adult patients in mini-bags; here we describe motivating factors and barriers faced by clinical staff. The secondary aim was to support the need for change and implementation of the international recommendations. Chemotherapy-certified nurses completed a survey spanning August 2009 to August 2011, to ascertain the incidence of extravasation associated with the administration of vincristine in mini-bags. This period captured 421 occasions of vincristine administration in 25-ml or 50-ml mini-bags (in 0.9% sodium chloride). The median age of patients was 13 years (range 2.5 months to 99 years). Vincristine was administered through peripheral lines (26.4%), portacath (52.0%), PICC line (15.9%) and Hickman line (5.7%). The majority of infusions were over at least 10 minutes (50.1%). There were no cases of extravasation reported. The administration of vincristine in small volume intravenous bags was safe, practical, and feasible in all patient groups. The successful implementation of the international recommendations for vincristine administration in mini-bags to eliminate potential inadvertent intrathecal administration was dependent on stakeholder buy-in. © The Author(s) 2014.

Repeated, but Not Acute, Stress Suppresses Inflammatory Plasma Extravasation

NASA Astrophysics Data System (ADS)

Strausbaugh, Holly J.; Dallman, Mary F.; Levine, Jon D.

1999-12-01

Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of plasma extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of plasma extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial plasma extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of plasma extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases.

Bone scintigraphy for neonatal osteomyelitis: simulation by extravasation of intravenous calcium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balsam, D.; Goldfarb, C.R.; Stringer, B.

Intravenously administered calcium gluconate has become increasingly popular in the treatment of neonatal tetany. Occasionally, extravasation results in cellulitis, leading to a clinical diagnosis of superimposed osteomyelitis. Osseous scintigraphy, as the accepted modality in the early detection of osteomyelitis, would tend to be used in this circumstance. This case illustrates a false-positive result, probably due to soft-tissue calcification.

Serotonin modulates substance P-induced plasma extravasation and vasodilatation in rat skin by an action through capsaicin-sensitive primary afferent nerves.

PubMed

Khalil, Z; Helme, R D

1990-09-17

Using a blister model of inflammation in the rat hind footpad, the present study was undertaken to examine the ability of serotonin (5-HT) to modulate an inflammatory reaction manifested as plasma extravasation and vasodilatation induced by the neuropeptide substance P (SP). In addition, the role of primary afferent sensory nerve fibres in these modulatory effects was studied in capsaicin pretreated rats. Using a protocol of simultaneous perfusion of amine and peptide over the blister base, no major modulatory effect was observed. On the other hand, using a protocol of sequential perfusion, 5-HT was found to extend the plasma extravasation and vasodilatation responses to SP. 5-HT maintained the plasma extravasation response to SP after cessation of stimulation (during the post-stimulation period). On the other hand, it extended the vasodilatation response to SP during the actual stimulation period by preventing the occurrence of tachyphylaxis. These modulatory effects were absent in capsacin-pretreated rats. The present study provides evidence for the first time in vivo to suggest that serotonin can modulate an inflammatory response to SP via a mechanism that involves capsaicin-sensitive sensory fibres.

Proteolysis during Tumor Cell Extravasation In Vitro: Metalloproteinase Involvement across Tumor Cell Types

PubMed Central

Voura, Evelyn B.; English, Jane L.; Yu, Hoi-Ying E.; Ho, Andrew T.; Subarsky, Patrick; Hill, Richard P.; Hojilla, Carlo V.; Khokha, Rama

2013-01-01

To test if proteolysis is involved in tumor cell extravasation, we developed an in vitro model where tumor cells cross an endothelial monolayer cultured on a basement membrane. Using this model we classified the ability of the cells to transmigrate through the endothelial cell barrier onto the underlying matrix, and scored this invasion according to the stage of passage through the endothelium. Metalloproteinase inhibitors reduced tumor cell extravasation by at least 35%. Visualization of protease and cell adhesion molecules by confocal microscopy demonstrated the cell surface localization of MMP-2, MMP-9, MT1-MMP, furin, CD44 and αvβ3, during the process of transendothelial migration. By the addition of inhibitors and bio-modulators we assessed the functional requirement of the aforementioned molecules for efficient migration. Proteolytic digestion occurred at the cell-matrix interface and was most evident during the migratory stage. All of the inhibitors and biomodulators affected the transition of the tumor cells into the migratory stage, highlighting the most prevalent use of proteolysis at this particular step of tumor cell extravasation. These data suggest that a proteolytic interface operates at the tumor cell surface within the tumor-endothelial cell microenvironment. PMID:24194929

Investigation of Tumor Cell Behaviors on a Vascular Microenvironment-Mimicking Microfluidic Chip

PubMed Central

Huang, Rong; Zheng, Wenfu; Liu, Wenwen; Zhang, Wei; Long, Yunze; Jiang, Xingyu

2015-01-01

The extravasation of tumor cells is a key event in tumor metastasis. However, the mechanism underlying tumor cell extravasation remains unknown, mainly hindered by obstacles from the lack of complexity of biological tissues in conventional cell culture, and the costliness and ethical issues of in vivo experiments. Thus, a cheap, time and labor saving, and most of all, vascular microenvironment-mimicking research model is desirable. Herein, we report a microfluidic chip-based tumor extravasation research model which is capable of simultaneously simulating both mechanical and biochemical microenvironments of human vascular systems and analyzing their synergistic effects on the tumor extravasation. Under different mechanical conditions of the vascular system, the tumor cells (HeLa cells) had the highest viability and adhesion activity in the microenvironment of the capillary. The integrity of endothelial cells (ECs) monolayer was destroyed by tumor necrosis factor-α (TNF-α) in a hemodynamic background, which facilitated the tumor cell adhesion, this situation was recovered by the administration of platinum nanoparticles (Pt-NPs). This model bridges the gap between cell culture and animal experiments and is a promising platform for studying tumor behaviors in the vascular system. PMID:26631692

Localization of near-infrared contrast agents in tumors by intravital microscopy

NASA Astrophysics Data System (ADS)

Becker, Andreas; Schneider, Guenther; Riefke, Bjoern; Licha, Kai; Semmler, Wolfhard

1999-01-01

In this contribution we use intravital microscopy to study the dynamics of extravasation into normal and tumor tissue of several hydrophilic cyanine dyes used as near-infrared (NIR) contrast agents. The technique provides information about the angiographic properties of the dyes and about their interaction with tumor tissue under dynamic conditions in vivo. In our previous work we demonstrated that several NIR- absorbing fluorescent dyes enable in vivo fluorescence detection of tumors in mice and rats. However, the mechanism leading to dye accumulation and enhanced fluorescence in tumors is not fully understood. Increased extravasation of dyes into tumor tissue due to pathologically altered tumor vessels may be an important factor in this process. Indocyanine green (ICG) displayed predominantly intravascular distribution and rapid elimination resulting in enhanced fluorescence signal of vessels during the first 15 min after administration only. No elevated extravasation into tumor tissue was observed with ICG. A hydrophilic indotricarbocyanine derivative with a high molecular weight displayed prolonged intravascular distribution and increased fluorescence signal of the vasculature compared to surrounding tissue for up to five hours. Rapid extravasation and accumulation in tumor areas, yielding elevated contrast of tumors up to 15 min after administration, was observed with hydrophilic, low molecular weight indotricarbocyanine derivatives.

Uropod elongation is a common final step in leukocyte extravasation through inflamed vessels

PubMed Central

Hyun, Young-Min; Sumagin, Ronen; Sarangi, Pranita P.; Lomakina, Elena; Overstreet, Michael G.; Baker, Christina M.; Fowell, Deborah J.; Waugh, Richard E.; Sarelius, Ingrid H.

2012-01-01

The efficient trafficking of immune cells into peripheral nonlymphoid tissues is key to enact their protective functions. Despite considerable advances in our understanding of cell migration in secondary lymphoid organs, real-time leukocyte recruitment into inflamed tissues is not well characterized. The conventional multistep paradigm of leukocyte extravasation depends on CD18 integrin–mediated events such as rapid arrest and crawling on the surface of the endothelium and transmigration through the endothelial layer. Using enhanced three-dimensional detection of fluorescent CD18 fusion proteins in a newly developed knockin mouse, we report that extravasating leukocytes (neutrophils, monocytes, and T cells) show delayed uropod detachment and become extremely elongated before complete transmigration across the endothelium. Additionally, these cells deposit CD18+ microparticles at the subendothelial layer before retracting the stretched uropod. Experiments with knockout mice and blocking antibodies reveal that the uropod elongation and microparticle formation are the result of LFA-1–mediated adhesion and VLA-3–mediated cell migration through the vascular basement membrane. These findings suggest that uropod elongation is a final step in the leukocyte extravasation cascade, which may be important for precise regulation of leukocyte recruitment into inflamed tissues. PMID:22711877

Lysosomal Degradation of CD44 Mediates Ceramide Nanoliposome-induced Anoikis and Diminished Extravasation in Metastatic Carcinoma Cells*

PubMed Central

Haakenson, Jeremy K.; Khokhlatchev, Andrei V.; Choi, Younhee J.; Linton, Samuel S.; Zhang, Pu; Zaki, Peter M.; Fu, Changliang; Cooper, Timothy K.; Manni, Andrea; Zhu, Junjia; Fox, Todd E.; Dong, Cheng; Kester, Mark

2015-01-01

The ceramide nanoliposome (CNL) has shown promise in being able to treat a variety of primary tumors. However, its potential for treating metastatic cancer remains unknown. In this study, we demonstrate that CNL increases anoikis while preventing cancer cell extravasation under both static and physiological fluid flow conditions. Mechanistically, CNL limits metastases by decreasing CD44 protein levels in human breast and pancreatic cancer cells via lysosomal degradation of CD44, independent of palmitoylation or proteasome targeting. siRNA down-regulation of CD44 mimics CNL-induced anoikis and diminished extravasation of cancer cells. Taken together, our data indicate that ceramide limits CD44-dependent cancer cell migration, suggesting that CNL could be used to prevent and treat solid tumor metastasis. PMID:25681441

Treatment of tissue extravasation by antitumor agents.

PubMed

Larson, D L

1982-05-01

Infiltration of antitumor agents into subcutaneous tissues may either result in a local area of self-resolving inflammation, or progress to full-thickness loss of skin and underlying vital structures. The immediate treatment of 50 extravasations occurring over a 20-month period resulted in our developing a protocol of appropriate care. Once extravasation is suspected, the intravenous line is removed, ice is applied intermittently for three days, and the wound is observed closely. No drugs are even given locally. If local pain persists or skin changes progress, the area of involvement is debrided and, a skin graft is applied two to three days later. As a result of this conservative approach, only 12 of 50 patients have required surgery. This method of treatment has minimized patient mortality, hospitalizations, and loss of synchronization of chemotherapy.

Fatal Primary Capillary Leak Syndrome in a Late Preterm Newborn.

PubMed

Kulihova, Katarina; Prochazkova, Martina; Semberova, Jana; Janota, Jan

2016-10-01

Primary capillary leak syndrome is a rare disease of unknown etiology, characterized by episodes of vascular collapse and plasma extravasation, which may lead to multiple organ failure. Primary capillary leak is extremely rare in children. The authors report a case of a late preterm newborn with fatal capillary leak syndrome of unknown etiology, manifesting as hypotension unresponsive to treatment, extravasation leading to generalised edema, disseminated intravascular coagulation and finally, multiple organ dysfunction syndrome. Aggressive volumotherapy and a combination of inotropes and high doses of terlipressin did not influence systemic vascular collapse and plasma extravasation. The newborn developed multiple organ failure and died on day 27 of life. Investigations performed failed to reveal any specific cause of capillary leak. This is the first report of a fatal primary capillary leak syndrome in a newborn.

Enhanced extravasation, stability and in vivo cardiac gene silencing via in situ siRNA-albumin conjugation.

PubMed

Lau, Shannen; Graham, Bim; Cao, Nga; Boyd, Ben J; Pouton, Colin W; White, Paul J

2012-01-01

A potential barrier to progression of siRNA therapeutics to the clinic is the ability of these agents to cross the vascular endothelium to reach target cells. This study aimed to bypass the endothelial barrier by harnessing the extravasation capability of the serum protein albumin to allow siRNA to reach cardiomyocytes. A strategy for conjugating siRNA to albumin in vivo was developed that involved activating 3'-amine, 2'-O-methyl, phosphorothioate modified siRNA with succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (SMCC) to yield maleimide-functionalized siRNA ("activated siRNA"); this thiol-reactive species can then irreversibly link to the single surface-exposed cysteine residue of endogenous albumin following intravenous administration. An IGF-I-receptor (IGF-IR) siRNA sequence which was effective in vitro was used to test the ability of the siRNA-albumin conjugate to bypass the endothelial barrier in Balb/C mice and produce silencing. In situ conjugation of maleimide-functionalized siRNA to albumin in mouse serum occurred within minutes of addition, and the resulting conjugate was found to be nuclease stable by SDS-PAGE analysis. In Sprague-Dawley rats, activated siRNA showed a significantly enhanced elimination half-life (75.9 ± 18.2 min) compared to unactivated siRNA (5.1 ± 0.2 min). Intravenous injection of this activated siRNA (1 mg/kg daily for four days) significantly reduced left ventricle IGF-IR mRNA to 64.1 ± 4.1% of that in vehicle-treated animals (mean ± SEM), while the control siRNA (unconjugated) had no effect (n = 4, P > 0.05). Imaging of microvessels from mice treated with fluorescein-labeled activated siRNA showed clear evidence of extravasation and cellular uptake in capillary endothelial cells, cardiomyocytes and vascular smooth muscle cells for mice treated with the activated siRNA but not mice treated with the unactivated siRNA. siRNA-albumin constructs are therefore capable of extravasation to the myocardium resulting in silencing in this otherwise silencing-resistant organ.

Effects of N-acetylcysteine and terbutaline treatment on hemodynamics and regional albumin extravasation in porcine septic shock

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groeneveld, A.B.; den Hollander, W.; Straub, J.

We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gamma camera and a computer until 5 hours after baseline. Regions of interestmore » were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C, confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C and T but not in N.« less

Fluid Extravasation in Shoulder Arthroscopic Surgery: A Systematic Review

PubMed Central

Memon, Muzammil; Kay, Jeffrey; Gholami, Arian; Simunovic, Nicole; Ayeni, Olufemi R.

2018-01-01

Background: Arthroscopic surgery of the shoulder joint has become increasingly more common given its advantages over open surgery; however, one rare but potentially life-threatening complication is fluid extravasation into the surrounding tissues, causing edema, respiratory compromise, abnormal results on laboratory blood tests, and possibly death. Currently, no systematic review exists that summarizes the existing clinical research on this topic. Purpose: To perform a systematic review on fluid extravasation as a complication of shoulder arthroscopic surgery, specifically assessing clinical presentation, risk factors, management, and outcomes. Study Design: Systematic review; Level of evidence, 4. Methods: Two reviewers independently searched 3 databases (PubMed, Ovid [MEDLINE], and Embase) from database inception until July 1, 2017. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist guided the reporting and data abstraction. The methodological quality of these studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist. The results are presented in a narrative summary fashion using descriptive statistics including ranges and agreement statistics. Results: A total of 26 studies (20 case reports, 4 case series, and 2 prospective comparative studies) encompassing 205 patients (mean age, 50.8 years [range, 15-83 years]) were included. The most common signs of fluid extravasation included chest wall swelling (n = 86) and neck swelling (n = 116). In 32 patients, observation alone was sufficient. Other patients required airway intubation (n = 16), diuretics (n = 7), steroids (n = 1), and percutaneous drainage of fluid (n = 1). Clinical edema resolved after 2 to 48 hours, and patients were discharged 1 to 20 days postoperatively. Serious complications included transfer to the intensive care unit (n = 14), anterior interosseous nerve palsy (n = 4), rhabdomyolysis (n = 1), and death (n = 1). Conclusion: Fluid extravasation has the potential to be a life-threatening complication of shoulder arthroscopic surgery; however, it is most commonly managed nonoperatively, and symptoms typically resolve with no evidence of long-term complications. Intraoperative surgical decisions, such as minimizing the surgical time and volume of irrigation fluid used, may limit fluid extravasation, while careful intraoperative monitoring may facilitate prompt diagnosis and management to optimize patient outcomes. PMID:29785406

Fluid extravasation during cardiopulmonary bypass in piglets--effects of hypothermia and different cooling protocols.

PubMed

Farstad, M; Heltne, J K; Rynning, S E; Lund, T; Mongstad, A; Eliassen, F; Husby, P

2003-04-01

Hypothermic cardiopulmonary bypass (CPB) is associated with capillary fluid leak and edema generation which may be secondary to hemodilution, inflammation and hypothermia. We evaluated how hypothermia and different cooling strategies influenced the fluid extravasation rate during CPB. Fourteen piglets were given 60 min normothermic CPB, followed by randomization to two groups: 1: rapid cooling (RC-group) ( approximately 15 min to 28 degrees C); 2: slow cooling (SC-group) ( approximately 60 min to 28 degrees C). Ringer's solution was used as CPB prime and for fluid supplementation. Fluid input/losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum-proteins and total tissue water (TTW) were measured and fluid extravasation rates calculated. Start of normothermic CPB resulted in a 25% hemodilution. During the first 5-10 min the fluid level of the reservoir fell markedly due to an intravascular volume loss necessitating fluid supplementation. Thereafter a steady state was reached with a constant fluid need of 0.14 +/- 0.04 ml kg-1 min-1. After start of cooling the fluid needs increased in the following 30 min to 0.91 +/- 0.11 ml kg-1 min-1 in the RC group (P < 0.001) and 0.63 +/- 0.10 ml kg-1 min-1 in the SC-group (P < 0.001) with no statistical between-group differences. Fluid extravasation rates after start of hypothermic CPB increased from 0.20 +/- 0.08 ml kg-1 min-1 to 0.71 +/- 0.13 (P < 0.01) and 0.62 +/- 0.13 ml kg-1 min-1 (P < 0.05) in the RC- and SC-groups, respectively, without any changes in degree of hemodilution. TTW increased in most tissues, whereas the intravascular albumin and protein masses remained constant with no between group differences. Hypothermia increased fluid extravasation during CPB independent of cooling strategy. Intravascular albumin and protein masses remained constant. Since inflammatory fluid leakage usually results in protein rich exudates, our data with no net protein leakage may indicate that mechanisms other than inflammation could contribute to fluid extravasation during hypothermic CPB.

Fluid Extravasation in Shoulder Arthroscopic Surgery: A Systematic Review.

PubMed

Memon, Muzammil; Kay, Jeffrey; Gholami, Arian; Simunovic, Nicole; Ayeni, Olufemi R

2018-05-01

Arthroscopic surgery of the shoulder joint has become increasingly more common given its advantages over open surgery; however, one rare but potentially life-threatening complication is fluid extravasation into the surrounding tissues, causing edema, respiratory compromise, abnormal results on laboratory blood tests, and possibly death. Currently, no systematic review exists that summarizes the existing clinical research on this topic. To perform a systematic review on fluid extravasation as a complication of shoulder arthroscopic surgery, specifically assessing clinical presentation, risk factors, management, and outcomes. Systematic review; Level of evidence, 4. Two reviewers independently searched 3 databases (PubMed, Ovid [MEDLINE], and Embase) from database inception until July 1, 2017. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist guided the reporting and data abstraction. The methodological quality of these studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) checklist. The results are presented in a narrative summary fashion using descriptive statistics including ranges and agreement statistics. A total of 26 studies (20 case reports, 4 case series, and 2 prospective comparative studies) encompassing 205 patients (mean age, 50.8 years [range, 15-83 years]) were included. The most common signs of fluid extravasation included chest wall swelling (n = 86) and neck swelling (n = 116). In 32 patients, observation alone was sufficient. Other patients required airway intubation (n = 16), diuretics (n = 7), steroids (n = 1), and percutaneous drainage of fluid (n = 1). Clinical edema resolved after 2 to 48 hours, and patients were discharged 1 to 20 days postoperatively. Serious complications included transfer to the intensive care unit (n = 14), anterior interosseous nerve palsy (n = 4), rhabdomyolysis (n = 1), and death (n = 1). Fluid extravasation has the potential to be a life-threatening complication of shoulder arthroscopic surgery; however, it is most commonly managed nonoperatively, and symptoms typically resolve with no evidence of long-term complications. Intraoperative surgical decisions, such as minimizing the surgical time and volume of irrigation fluid used, may limit fluid extravasation, while careful intraoperative monitoring may facilitate prompt diagnosis and management to optimize patient outcomes.

On-chip human microvasculature assay for visualization and quantitation of tumor cell extravasation dynamics

PubMed Central

Chen, Michelle B.; Whisler, Jordan A.; Fröse, Julia; Yu, Cathy; Shin, Yoojin

2017-01-01

Distant metastasis, which results in >90% of cancer related deaths, is enabled by hematogenous dissemination of tumor cells via the circulation. This requires the completion of a sequence of complex steps including transit, initial arrest, extravasation, survival and proliferation. Increased understanding of the cellular and molecular players enabling each of these steps is key in uncovering new opportunities for therapeutic intervention during early metastatic dissemination. Here, we describe an in vitro model of the human microcirculation with the potential to recapitulate discrete steps of early metastatic seeding, including arrest, transendothelial migration and early micrometastases formation. The microdevice features self-organized human microvascular networks formed over 4–5 days, after which tumor can be perfused and extravasation events easily tracked over 72 hours, via standard confocal microscopy. Contrary to most in vivo and in vitro extravasation assays, robust and rapid scoring of extravascular cells combined with high-resolution imaging can be easily achieved due to the confinement of the vascular network to one plane close to the surface of the device. This renders extravascular cells clearly distinct and allows tumor cells of interest to be identified quickly compared to those in thick tissues. The ability to generate large numbers of devices (~36) per experiment coupled with fast quantitation further allows for highly parametric studies, which is required when testing multiple genetic or pharmacological perturbations. This is coupled with the capability for live tracking of single cell extravasation events allowing both tumor and endothelial morphological dynamics to be observed in high detail with a moderate number of data points. This Protocol Extension describes an adaptation of an existing Protocol describing a microfluidic platform that offers additional applications. PMID:28358393

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein.

PubMed

Kumar, Devender; Ristow, Laura C; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

2015-12-01

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration.

Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein

PubMed Central

Kumar, Devender; Ristow, Laura C.; Shi, Meiqing; Mukherjee, Priyanka; Caine, Jennifer A.; Lee, Woo-Yong; Kubes, Paul; Coburn, Jenifer; Chaconas, George

2015-01-01

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d -/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration. PMID:26684456

Thermographic visualization of the superficial vein and extravasation using the temperature gradient produced by the injected materials

NASA Astrophysics Data System (ADS)

Nakamura, Katsumasa; Sasaki, Tomonari; Ohga, Saiji; Yoshitake, Tadamasa; Terashima, Kotaro; Asai, Kaori; Matsumoto, Keiji; Shinoto, Makoto; Shioyama, Yoshiyuki; Nishie, Akihoro; Honda, Hiroshi

2014-11-01

There are few effective methods to detect or prevent the extravasation of injected materials such as chemotherapeutic agents and radiographic contrast materials. To investigate whether a thermographic camera could visualize the superficial vein and extravasation using the temperature gradient produced by the injected materials, an infrared thermographic camera with a high resolution of 0.04 °C was used. At the room temperature of 26 °C, thermal images and the time course of the temperature changes of a paraffin phantom embedded with rubber tubes (diameter 3.2 mm, wall thickness 0.8 mm) were evaluated after the tubes were filled with water at 15 °C or 25 °C. The rubber tubes were embedded at depths of 0 mm, 1.5 mm, and 3.0 mm from the surface of the phantom. Temperature changes were visualized in the areas of the phantom where the tubes were embedded. In general, changes were more clearly detected when greater temperature differences between the phantom and the water and shallower tube locations were employed. The temperature changes of the surface of a volunteer's arm were also examined after a bolus injection of physiological saline into the dorsal hand vein or the subcutaneous space. The injection of 5 ml room-temperature (26 °C) saline into the dorsal hand vein enabled the visualization of the vein. When 3 ml of room-temperature saline was injected through the vein into the subcutaneous space, extravasation was detected without any visualization of the vein. The subtraction image before and after the injection clearly showed the temperature changes induced by the saline. Thermography may thus be useful as a monitoring system to detect extravasation of the injected materials.

A Primer on the Acute Management of Intravenous Extravasation Injuries for the Plastic Surgeon

PubMed Central

Maly, Connor; Fan, Kenneth L.; Rogers, Gary F.; Mitchell, Benjamin; Amling, June; Johnson, Kara; Welch, Laura; Oh, Albert K.

2018-01-01

Intravenous therapy is a common practice among many specialties. Intravenous therapy extravasation is a potential complication to such therapy. Hospitals without a dedicated wound care team trained in these interventions will often default to plastic surgical consultation, making an understanding of available interventions essential to the initial evaluation and management of these injuries. The goal of this article was to provide plastic surgeons and health care providers with a general overview of the acute management of intravenous infiltration and extravasation injuries. Though the decision for surgical versus nonsurgical management is often a clear one for plastic surgeons, local interventions, and therapies are often indicated and under-utilized in the immediate postinfiltration period. Thorough knowledge of these interventions should be a basic requirement in the armamentarium of plastic surgery consultants. PMID:29876181

Gadolinium-Based Contrast Agent Extravasation Mimicking Subarachnoid Hemorrhage After Electroconvulsive Therapy.

PubMed

Taydas, Onur; Ogul, Hayri; Ozcan, Halil; Kantarci, Mecit

2018-06-01

Electroconvulsive therapy (ECT) is a safe method that has been applied for many years in medical treatment-resistant depression treatment. In this case report, contrast extravasation due to deterioration of the blood-brain barrier after ECT mimicking subarachnoid hemorrhage (SAH) on magnetic resonance imaging (MRI) is discussed. A 70-year-old male patient who underwent ECT presented with sulcal hyperintensities suggesting subarachnoid hemorrhage on fluid-attenuated inversion recovery sequence of MRI obtained after ECT. However, there was no evidence to suggest SAH on nonenhanced brain computed tomography. It should be kept in mind that patients may have contrast extravasation due to deterioration of the blood-brain barrier after ECT, and other alternative methods should be used for the diagnosis of SAH in these patients, not MRI. Copyright © 2018 Elsevier Inc. All rights reserved.

In vivo monitoring of distributional transport kinetics and extravasation of quantum dots in living rat liver

NASA Astrophysics Data System (ADS)

Su, Cheng-Kuan; Sun, Yuh-Chang

2013-04-01

Although the unique optical properties of surface-modified quantum dots (QDs) have attracted wide interest in molecular biology and bioengineering, there are very few reports of their in vivo biodistribution, due to a lack of analytical techniques for characterizing the dynamic variation of QDs in living animals. In this study, we used an in vivo online monitoring system and a batch-wise elemental analytical method to investigate the biodistribution/extravasation of various surface-modified CdTeSe/ZnS (QDs) in rat liver. It is found that the surface modification dictated not only the blood retention profile but also the degree of extravasation and the clearance of extracellular QDs, making it an important variable for regulating the transfer and exchange process of QDs among three physiological compartments—bloodstream, extracellular space and Kupffer cells/hepatocytes.

Lysosomal degradation of CD44 mediates ceramide nanoliposome-induced anoikis and diminished extravasation in metastatic carcinoma cells.

PubMed

Haakenson, Jeremy K; Khokhlatchev, Andrei V; Choi, Younhee J; Linton, Samuel S; Zhang, Pu; Zaki, Peter M; Fu, Changliang; Cooper, Timothy K; Manni, Andrea; Zhu, Junjia; Fox, Todd E; Dong, Cheng; Kester, Mark

2015-03-27

The ceramide nanoliposome (CNL) has shown promise in being able to treat a variety of primary tumors. However, its potential for treating metastatic cancer remains unknown. In this study, we demonstrate that CNL increases anoikis while preventing cancer cell extravasation under both static and physiological fluid flow conditions. Mechanistically, CNL limits metastases by decreasing CD44 protein levels in human breast and pancreatic cancer cells via lysosomal degradation of CD44, independent of palmitoylation or proteasome targeting. siRNA down-regulation of CD44 mimics CNL-induced anoikis and diminished extravasation of cancer cells. Taken together, our data indicate that ceramide limits CD44-dependent cancer cell migration, suggesting that CNL could be used to prevent and treat solid tumor metastasis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of carbamazepine on plasma extravasation and bronchoconstriction induced by substance P, capsaicin, acetaldehyde and histamine in guinea-pig lower airways.

PubMed

Bianchi, M; Rossoni, G; Maggi, R; Panerai, A E; Berti, F

1998-01-01

We evaluated the in vivo effects of the pretreatment with carbamazepine (CBZ) at different doses (10, 20 and 40 mg/kg p.o.) on the Evans-blue extravasation and on bronchoconstriction induced by different substances in guinea-pig tracheal tissue. The drug dose-dependently inhibited the extravasation induced by substance P (SP), capsaicin and acetaldehyde, but not that induced by histamine. At the highest dose (40 mg/kg) CBZ inhibited the bronchoconstriction induced by SP, capsaicin and acetaldehyde, but not that produced by histamine administration. The in vitro study with guinea-pig tracheal preparation indicates that the drug does not interfere with the binding of SP to its receptors. Our results suggest that CBZ exerts a protective activity against the pro-inflammatory action of SP.

Dexrazoxane for the prevention of cardiac toxicity and treatment of extravasation injury from the anthracycline antibiotics.

PubMed

Doroshow, James H

2012-08-01

The cumulative cardiac toxicity of the anthracycline antibiotics and their propensity to produce severe tissue injury following extravasation from a peripheral vein during intravenous administration remain significant problems in clinical oncologic practice. Understanding of the free radical metabolism of these drugs and their interactions with iron proteins led to the development of dexrazoxane, an analogue of EDTA with intrinsic antineoplastic activity as well as strong iron binding properties, as both a prospective cardioprotective therapy for patients receiving anthracyclines and as an effective treatment for anthracycline extravasations. In this review, the molecular mechanisms by which the anthracyclines generate reactive oxygen species and interact with intracellular iron are examined to understand the cardioprotective mechanism of action of dexrazoxane and its ability to protect the subcutaneous tissues from anthracycline-induced tissue necrosis.

Diagnosis and Treatment of Heterotopic Ossification

DTIC Science & Technology

2014-10-01

junction molecule that regulates the “blood-nerve barrier”. These cells also now express the markers of extravasation , CD44 and CXCR4. These cells then...with these stem cells then entering the blood stream. During bone injury, they are recruited to the site of bone formation. Thus, there are many drugs ...bloodstream simultaneously with an increase in expression of factors involved in extravasation and the appearance of the osterix+ claudin 5

Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

DTIC Science & Technology

2015-09-01

hypothesize that after extravasation at secondary site TMEM (S- TMEM), in order to exit dormancy a stable S-TMEM structure needs to be maintained and...by understanding early dissemination and dormancy of DTCs we will find ways to eradicate dormant DTCs and prevent metastasis. 2. KEYWORDS...TMEM, DTC, dormancy, dissemination intravasation, extravasation 3. ACCOMPLISHMENTS:  What were the major goals of the project? Our original specific

Optimization of Evans blue quantitation in limited rat tissue samples

PubMed Central

Wang, Hwai-Lee; Lai, Ted Weita

2014-01-01

Evans blue dye (EBD) is an inert tracer that measures plasma volume in human subjects and vascular permeability in animal models. Quantitation of EBD can be difficult when dye concentration in the sample is limited, such as when extravasated dye is measured in the blood-brain barrier (BBB) intact brain. The procedure described here used a very small volume (30 µl) per sample replicate, which enabled high-throughput measurements of the EBD concentration based on a standard 96-well plate reader. First, ethanol ensured a consistent optic path length in each well and substantially enhanced the sensitivity of EBD fluorescence spectroscopy. Second, trichloroacetic acid (TCA) removed false-positive EBD measurements as a result of biological solutes and partially extracted EBD into the supernatant. Moreover, a 1:2 volume ratio of 50% TCA ([TCA final] = 33.3%) optimally extracted EBD from the rat plasma protein-EBD complex in vitro and in vivo, and 1:2 and 1:3 weight-volume ratios of 50% TCA optimally extracted extravasated EBD from the rat brain and liver, respectively, in vivo. This procedure is particularly useful in the detection of EBD extravasation into the BBB-intact brain, but it can also be applied to detect dye extravasation into tissues where vascular permeability is less limiting. PMID:25300427

Transport of Brownian spheroidal nanoparticles in near-wall vascular flows for cancer therapy

NASA Astrophysics Data System (ADS)

Lin, Tiras Y.; Shah, Preyas N.; Smith, Bryan R.; Shaqfeh, Eric S. G.

2016-11-01

The microenvironment local to a tumor is characterized by a leaky vasculature induced by angiogenesis from tumor growth. Small pores form in the blood vessel walls, and these pores provide a pathway for cancer-ameliorating nanoparticle drug carriers. Using both simulations and microfluidics experiments, we investigate the extravasation of nanoparticles through pores. Using Brownian dynamics simulations, we evolve the stochastic equations for both point particles and finite-size spheroids of varying aspect ratio. We investigate the effect of wall shear flow and pore suction flow (Sampson flow) on the extravasation process. We consider pores of two types: physiologically relevant short pores with a length equal to the particle size and long pores which are relevant to diffusion through membranes. Additionally, we perform microfluidics experiments in which the extravasation rates of various nanoparticles tagged with fluorescent dye through pores are measured. In particular, using fluorometry we measure the flux of nanoparticles across a track-etched membrane, which separates two chambers. Our preliminary results indicate that the flux measured from experiment agrees reasonably with the simulations done with long pores, and we discuss the effect of pore length on extravasation. T.Y.L. is supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

Optimization of Evans blue quantitation in limited rat tissue samples

NASA Astrophysics Data System (ADS)

Wang, Hwai-Lee; Lai, Ted Weita

2014-10-01

Evans blue dye (EBD) is an inert tracer that measures plasma volume in human subjects and vascular permeability in animal models. Quantitation of EBD can be difficult when dye concentration in the sample is limited, such as when extravasated dye is measured in the blood-brain barrier (BBB) intact brain. The procedure described here used a very small volume (30 µl) per sample replicate, which enabled high-throughput measurements of the EBD concentration based on a standard 96-well plate reader. First, ethanol ensured a consistent optic path length in each well and substantially enhanced the sensitivity of EBD fluorescence spectroscopy. Second, trichloroacetic acid (TCA) removed false-positive EBD measurements as a result of biological solutes and partially extracted EBD into the supernatant. Moreover, a 1:2 volume ratio of 50% TCA ([TCA final] = 33.3%) optimally extracted EBD from the rat plasma protein-EBD complex in vitro and in vivo, and 1:2 and 1:3 weight-volume ratios of 50% TCA optimally extracted extravasated EBD from the rat brain and liver, respectively, in vivo. This procedure is particularly useful in the detection of EBD extravasation into the BBB-intact brain, but it can also be applied to detect dye extravasation into tissues where vascular permeability is less limiting.

Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat.

PubMed

Bester, H; Allchorne, A J; Woolf, C J

1998-12-01

Peripheral nerve injury leads to substantial alterations in injured sensory neurons. These include cell death, phenotypic modifications, and regeneration. Primary sensory neurons have recently been shown not to die until a time beyond 4 months following a nerve crush or ligation and this loss is, moreover, limited to cells with unmyelinated axons, the C-fibers. The late loss of C-fibers may be due to a lack of target reinnervation during the regenerative phase. In order to investigate this, we have used a particular peripheral function, unique to C-fibers, as a measure of peripheral reinnervation: an increase in capillary permeability on antidromic activation of C-fibers, i.e., neurogenic extravasation. This was investigated in rats that had received a nerve crush injury 1 to 50 weeks earlier. Some recovery of the capacity of C-fibers to generate extravasation was detected at 8-10 weeks, which increased further at 12-14 weeks, and then plateaued at this level with no further recovery at 30 or 50 weeks. In intact and damaged sciatic nerves, A beta-fibers never induced extravasation. These findings are compatible with the hypothesis that those C-fibers which make it back to their peripheral targets do not subsequently die and those that do not, may die. Copyright 1998 Academic Press.

The effect of local compression and topical epinephrine on perioperative bleeding and degree of urinary extravasation on postoperative cystogram following radical retropubic prostatectomy.

PubMed

Malik, Rena; Laze, Juliana; Lepor, Herbert

2010-08-01

To evaluate the efficacy of local compression and topical epinephrine in controlling perioperative bleeding during open radical retropubic prostatectomy (ORRP) and its impact on the degree of urinary extravasation on initial postoperative cystogram. Between September 2005 to March 2009, 476 men underwent ORRP performed by a single surgeon. Group 1 (n = 200) underwent ORRP between September 2005 and November 2006 without pelvic compression; Group 2 (n = 76) underwent ORRP between November 2006 and May 2007 and a dry laparotomy pad was positioned in the pelvis immediately prior to abdominal wound closure; Group 3 (n = 200) underwent ORRP between May 2007 and March 2009 with a epinephrine soaked laparotomy pad positioned in the pelvis prior to abdominal wound closure. Hematocrit values were obtained prior to anesthesia induction, upon arrival in the recovery room and at hospital discharge in order to estimate intraoperative and postoperative bleeding. The number of allogenic and autologous units transfused was recorded. The utility of compressing the pelvis with a pad was examined by comparing estimated postoperative bleeding between Group 1 versus Groups 2 and 3 and the hemostatic utility of soaking the pad in epinephrine was examined by comparing Group 2 versus 3. Systolic and diastolic blood pressure and pulse measurements were obtained at baseline and 5 and 10 minutes after introducing the epinephrine pad. The relationship between estimated blood loss and degree of extravasation on initial postoperative cystogram was investigated. Estimated intraoperative, postoperative and total blood loss (mean change in Hct) was 12.2, 2.3, 14.2, in Group 1, 10.0, 1.5, 11.1 in Group 2, and 10.8, 2.1, and 12.6 in Group 3. Estimated intraoperative and total blood loss was significantly less in the men treated with a compression pad (Groups 2 and 3) versus no pad (Group 1). There were no significant differences in number of patients transfused, the number of units transfused or the degree of extravasation on postoperative cystograms between Group 1 versus Group 2 and 3 or Group 2 versus 3. However, postoperative bleeding was significantly less in Group 2 compared to Group 3. Mean systolic and diastolic blood pressure and pulse values were unchanged from baseline after epinephrine use. Local compression of the pelvis with or without epinephrine prior to abdominal wound closure does not appear to have beneficial effects on reducing postoperative bleeding and decreasing the degree of urinary extravasation on cystogram following ORRP. While the use of topical epinephrine appears to be safe and relatively inexpensive, at the concentrations used in our study it does not appear to facilitate postoperative hemostasis.

Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig.

PubMed Central

Lötvall, J. O.; Elwood, W.; Tokuyama, K.; Barnes, P. J.; Chung, K. F.

1991-01-01

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators. PMID:1725766

Differential effects of phosphoramidon on neurokinin A- and substance P-induced airflow obstruction and airway microvascular leakage in guinea-pig.

PubMed

Lötvall, J O; Elwood, W; Tokuyama, K; Barnes, P J; Chung, K F

1991-12-01

1. The effects of the inhaled neuropeptides, neurokinin A (NKA) and substance P (SP) on lung resistance (RL) and airway microvascular permeability were studied in anaesthetized guinea-pigs. 2. Single doses of inhaled NKA (3 x 10(-5), 1 x 10(-4), 3 x 10(-4) M; 45 breaths) and SP (1 x 10(-4), 3 x 10(-4), 1 x 10(-3); 45 breaths) caused a dose-dependent increase in both RL and airway microvascular leakage, assessed as extravasation of the albumin marker, Evans blue dye. 3. NKA at 1 x 10(-4) and 3 x 10(-4) M resulted in a significantly higher increase in RL than SP at the same doses. 4. Inhaled SP (3 x 10(-4) M; 45 breaths) caused significantly higher Evans blue dye extravasation in main bronchi and proximal intrapulmonary airways compared to the same dose of NKA. 5. Pretreatment with the specific inhibitor of neural endopeptidase (NEP24.11), phosphoramidon, caused an approximately 100 fold leftward shift of the RL responses to inhaled NKA and SP. 6. Phosphoramidon significantly potentiated both NKA- and SP-induced airway microvascular leakage at proximal intrapulmonary airways, but not at any other airway level. 7. Inhibition of NEP24.11 potentiate both the SP- or NKA-induced airflow obstruction to a larger extent than the induced airway microvascular leakage, suggesting that NEP24.11 is more important in the modulation of the airflow obstruction observed after these mediators.

Extravasation from venous catheter: a serious complication potentially missed by lung imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spicer, K.M.; Gordon, L.

Three patients were referred for lung ventiliation and perfusion (V/Q) imaging with symptoms strongly suggestive of pulmonary embolus (PE). Chest roentgenograms and xenon ventilation studies on all three were normal, save for prominent mediastinal silhouettes and effusions. Technetium-99m macroaggregated albumin(Tc-99m MAA), when injected through the central venous catheter (CVP), revealed mediastinal localization, whereas antecubital injections showed normal pulmonary perfusion. Contrast fluoroscopy introduced through the venous catheter in the first patient defined the extravasation. For patients under strong suspicion of PE, with a venous catheter whose distal tip is seen about the level of the heart on chest radiograph, the authorsmore » recommend administering the perfusion agent slowly through the central catheter to exclude catheter-induced complications. When extravasation is detected, injection of Tc-99m MAA by peripheral vein should be used to exclude PE.« less

IDACstar: A MCNP Application to Perform Realistic Dose Estimations from Internal or External Contamination of Radiopharmaceuticals.

PubMed

Ören, Ünal; Hiller, Mauritius; Andersson, M

2017-04-28

A Monte Carlo-based stand-alone program, IDACstar (Internal Dose Assessment by Computer), was developed, dedicated to perform radiation dose calculations using complex voxel simulations. To test the program, two irradiation situations were simulated, one hypothetical contamination case with 600 MBq of 99mTc and one extravasation case involving 370 MBq of 18F-FDG. The effective dose was estimated to be 0.042 mSv for the contamination case and 4.5 mSv for the extravasation case. IDACstar has demonstrated that dosimetry results from contamination or extravasation cases can be acquired with great ease. An effective tool for radiation protection applications is provided with IDACstar allowing physicists at nuclear medicine departments to easily quantify the radiation risk of stochastic effects when a radiation accident has occurred. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Alternative Pharmacological Management of Vasopressor Extravasation in the Absence of Phentolamine

PubMed Central

Plum, Michelle; Moukhachen, Oussayma

2017-01-01

Vasopressor extravasation is a rare adverse drug reaction that can lead to tissue damage, ischemia, and necrosis of the affected area when vasopressors are administered peripherally. Phentolamine, a nonselective, reversible alpha antagonist, is the current standard treatment for this adverse reaction, but it is often unavailable for use. This review seeks to synthesize the available data in order to recommend alternative pharmacological options for use when phentolamine is not available. After an extensive literature search, 16 publications were reviewed. A treatment algorithm was created that recommends a combination of subcutaneous terbutaline, a selective beta2 agonist, and topical nitroglycerin, an organic nitrate, for adults; and topical nitroglycerin monotherapy for children younger than 2 years of age. However, further research and case reports are required in order to establish a new standard of care for the treatment of vasopressor extravasation. PMID:28890646

Albumin extravasation and tissue washout of hyaluronan after plasma volume expansion with crystalloid or hypooncotic colloid solutions.

PubMed

Berg, S; Golster, M; Lisander, B

2002-02-01

Intravascular volume expansion is followed by loss of fluid from the circulation. The extravasation of albumin in this readjustment is insufficiently known. Twelve male volunteers participated, each in three separate sessions, in a controlled, randomised, open fashion. They received one of the following: albumin 40 g/L,(7.1 mL/kg, i.e. 500 mL per 70 kg); Ringer's acetate (21.4 mL/kg), or dextran 30 g/L (7.1 mL/kg). The fluids were infused during 30 min and the subjects were followed for 180 min. ECG, arterial oxygen saturation and non-invasive arterial pressure were recorded. Haemoglobin, haematocrit, serum albumin and osmolality, plasma colloid osmotic pressure and hyaluronan concentration were determined in venous samples. The serum albumin concentration decreased (P < 0.05, anova) following Ringer's acetate or dextran, whereas serum osmolality was unchanged in all groups. The colloid osmotic pressure decreased (P < 0.05) after the Ringer solution. The blood volume increase was estimated from the decrease in haemoglobin concentration and did not differ between the three fluids. The cumulated extravasation of albumin was largest following albumin (10.4 +/- 5.4 g, mean +/- SD), less following dextran (5.6 +/- 5.0 g) and negligible in the Ringer group (0.5 +/- 10.0 g; P < 0.05 against albumin). However, the Ringer solution increased the plasma concentration of hyaluronan drastically. Infusion of hypotonic colloidal solutions entails net loss of albumin from the vascular space. This is not the case after Ringer's acetate. Increased interstitial hydration from the latter fluid is followed by lymphatic wash out of hyaluronan.

Rate of contrast material extravasations and allergic-like reactions: effect of extrinsic warming of low-osmolality iodinated CT contrast material to 37 degrees C.

PubMed

Davenport, Matthew S; Wang, Carolyn L; Bashir, Mustafa R; Neville, Amy M; Paulson, Erik K

2012-02-01

To retrospectively determine whether extrinsic warming of the low-osmolality contrast material iopamidol to 37°C prior to intravenous administration at computed tomography (CT) affects extravasation and allergic-like reaction rates. The need to obtain informed patient consent was waived for this HIPAA-compliant and institutional review board-approved analysis. All adverse events related to the intravenous administration of iopamidol during CT examinations occurring 200 days before (period 1) and 200 days after (period 2) the cessation of extrinsic contrast material warming (37°C) for intravenous injections of less than 6 mL/sec at Duke University Medical Center (Durham, NC) were retrospectively reviewed. Adverse event rates were compared by using χ2 statistics. There were 12,682 injections during period 1 (10,831 injections of iopamidol 300 and 1851 injections of iopamidol 370) and 12,138 injections (10, 064 injections of iopamidol 300 and 2074 injections of iopamidol 370) during period 2. Adverse event rates for iopamidol 300 were not affected by extrinsic warming (extravasation rates: 0.30% [32 of 10,831] in period 1 vs 0.23% [23 of 10,064] in period 2, P=.64; allergic-like reaction rates: 0.39% [42 of 10,831] in period 1 vs 0.46% [46 of 10,064] in period 2, P=.74; overall adverse events: 0.68% [74 of 10,831] in period 1 vs 0.69% [69 of 10,064] in period 2, P=.99). Discontinuation of extrinsic warming was associated with significantly increased extravasation and overall adverse event rates for iopamidol 370 (extravasation rates: 0.27% [five of 1851] vs 0.87% [18 of 2074], P=.05; allergic-like reaction rates: 0.16% [three of 1851] vs 0.39% [eight of 2074], P=.42; overall adverse events: 0.43% [eight of 1851] vs 1.25% [26 of 2074], P=.02). Extrinsic warming (to 37°C) does not appear to affect adverse event rates for intravenous injections of iopamidol 300 of less than 6 mL/sec but is associated with a significant reduction in extravasation and overall adverse event rates for the more viscous iopamidol 370. © RSNA, 2011

Cinanserin reduces plasma extravasation after burn plasma transfer in rats.

PubMed

Hernekamp, Jochen-Frederick; Hu, Sissi; Schmidt, Karsten; Walther, Andreas; Kneser, Ulrich; Kremer, Thomas

2013-09-01

Thermal injuries greater than 20% body surface area (BSA) lead to systemic edema and hypovolemic shock. Capillary leakage is induced by different immunomodulative cytokines. Serotonin (5-HT) plays an important role in inflammation, vasodilatation and vasoconstriction and many other pathways such as systemic inflammation in endotoxemia and burns. Cinanserin, a specific 5-HT2 receptor blocking agent was administered to observe whether burn induced systemic edema can be reduced. Donor animals underwent thermal injury (100°C water, 30% BSA, 12s) for positive controls and negative controls underwent a shamburn procedure (37°C water, 30% BSA, 12s). Donor rat-plasma was transferred to healthy individuals after bolus injection of Cinanserin (5mg/kg body weight) was performed in recipient animals. Intravital microscopy was performed in mesenteric venules (0/60/120min) to asses systemic edema by FITC-albumin extravasation. Additionally, leukocyte activation (cells/mm(2)) was observed. Burnplasma-transfer results in systemic capillary leakage that is not observed in sham burn controls. Intraveneous application of Cinanserin significantly reduces systemic burn edema to shamburn levels. Leukocyte-endothelial interactions are significantly reduced by administration of Cinanserin. Specific 5-HT2 antagonism reduces systemic burn edema and leukocyte activation after plasma transfer. Reduction of capillary leakage may be partially mediated by leukocyte dependent as well as independent mechanisms. Future studies need to evaluate specific 5-HT2 receptor subtypes to distinguish between local and systemic effects of serotonin antagonists. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Probing Tumor Microenvironment with In Vivo Phage Display

DTIC Science & Technology

2014-09-01

becomes so dense that it blocks the access of anti-tumor drugs to tumor cells (Kalluri and Zeisberg, 2006; Sund and Kalluri, 2009). Tumor vessels are...together with synthetic iRGD peptide or 15 min after iRGD injection to facilitate extravasation of the phage pool within the breast tumor tissue. Co...populations within the tumor tissue (arrows). 6 Co-injection of non-labeled iRGD peptide enhanced the extravasation of FAM-CIS into the tumor

CT of trauma to the abnormal kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rhyner, P.; Federle, M.P.; Jeffrey, R.B.

Traumatic injuries to already abnormal kidneys are difficult to assess by excretory urography and clinical evaluation. Bleeding and urinary extravasation may accompany minor trauma; conversely, underlying tumors, perirenal hemorrhage, and extravasation may be missed on urography. Computed tomography (CT) was performed in eight cases including three neoplasms, one adult polycystic disease, one simple renal cyst, two hydronephrotic kidneys, and one horseshoe kidney. CT provided specific and clinically useful information in each case that was not apparent on excretory urography.

Successful Embolization of a Renal Artery Pseudoaneurysm with Arteriovenous Fistula and Extravasations Using Onyx After Partial Nephrectomy for Renal Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zelenak, Kamil, E-mail: zelenak@mfn.s; Sopilko, Igor; Svihra, Jan

2009-01-15

Partial nephrectomy can be associated with vascular complications. Computed tomography (CT) with CT angiography is ideal for noninvasive imaging of this process. The treatment of choice is selective embolization. Successful transcatheter embolization of right renal subsegmental artery pseudoaneurysm with arteriovenous fistula and extravasations using Onyx was performed in a 66-year-old woman with macrohematuria 12 days after partial nephrectomy for renal cell carcinoma.

Chemotherapy Extravasation Management: 21-Year Experience.

PubMed

Onesti, Maria Giuseppina; Carella, Sara; Fioramonti, Paolo; Scuderi, Nicolò

2017-11-01

Chemotherapy extravasation may result in serious damage to patients, with irreversible local injures and disability. Evidence-based standardization on extravasation management is lacking and many institutions do not practice adequate procedures to prevent the severer damages. Our aim was to explore the prevention and treatment of extravasation injuries, proposing a standard therapeutic protocol together with a review of the literature. From January 1994 to December 2015, 545 cases were reviewed (age range, 5-87 years; 282 men and 263 women). Our therapeutic protocol consisted of local infiltration of saline solution and topical occlusive applications of corticosteroids. The infiltrations were administrated 3 to 6 times a week depending on damage severity. Our protocol allowed us to prevent ulceration in 373 cases. Only 27 patients required surgery (escarectomy, skin graft, regional, and free flap). Numerous treatments have been proposed in literature. The antidotes have been discussed controversially and are not considered standard methods for treatment, especially when polychemotherapy is administrated and the identification of the responsible drug is not possible. We proposed the use of saline solution injection to dilute rapidly the drug, thus reducing its local toxic effects. This method is easy to use and always reproducible even when the drug is not known or when it is administrated in combination with other drugs. It is possible to perform it in ambulatory regimen, and, overall, it represents a standard method.

Isoflurane in contrast to propofol promotes fluid extravasation during cardiopulmonary bypass in pigs.

PubMed

Brekke, Hege Kristin; Hammersborg, Stig Morten; Lundemoen, Steinar; Mongstad, Arve; Kvalheim, Venny Lise; Haugen, Oddbjørn; Husby, Paul

2013-10-01

A highly positive intraoperative fluid balance should be prevented as it negatively impacts patient outcome. Analysis of volume-kinetics has identified an increase in interstitial fluid volume after crystalloid fluid loading during isoflurane anesthesia. Isoflurane has also been associated with postoperative hypoxemia and may be associated with an increase in alveolar epithelial permeability, edema formation, and hindered oxygen exchange. In this article, the authors compare fluid extravasation rates before and during cardiopulmonary bypass (CPB) with isoflurane- versus propofol-based anesthesia. Fourteen pigs underwent 2 h of tepid CPB with propofol (P-group; n = 7) or isoflurane anesthesia (I-group; n = 7). Fluid requirements, plasma volume, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded, and fluid extravasation rates calculated. Fluid extravasation rates increased in the I-group from the pre-CPB level of 0.27 (0.13) to 0.92 (0.36) ml·kg·min, but remained essentially unchanged in the P-group with significant between-group differences during CPB (pb = 0.002). The results are supported by corresponding changes in interstitial colloid osmotic pressure and total tissue water content. During CPB, isoflurane, in contrast to propofol, significantly contributes to a general increase in fluid shifts from the intravascular to the interstitial space with edema formation and a possible negative impact on postoperative organ function.

Antineoplastic agents extravasation from peripheral intravenous line in children: a simple strategy for a safer nursing care.

PubMed

Chanes, Daniella Cristina; da Luz Gonçalves Pedreira, Mavilde; de Gutiérrez, Maria Gaby Rivero

2012-02-01

The antineoplastic agents infusion through peripheral lines may lead to several adverse events such as extravasation that is one of the most severe acute reactions of this sort of treatment. The extravasation prevention and management must be part of a safe and evidence-based nursing care. Due to this fact, two algorithms were developed with the purpose of guiding nursing care to children who undergo chemotherapy through peripheral line. The objectives of this study were to determine the content validity of both algorithms with pediatric oncology nurses in Brazil and United States of America, and to verify the agreement between the evaluations of both groups. A descriptive validation study was carried out through the Delphi Technique that has the following steps: development of the data collection instrument, application to the specialists, data analysis, algorithms' review, re-evaluation by the specialists, final data analysis and content validity determination. The data analysis was descriptive and based on the specialists agreement consensus equal or higher than 80% in every step of the algorithms. The process showed that the agreement with both instruments ranged from 92.8% to 99.0%. The algorithms are valid for application in nursing care with the main purpose of preventing and managing the antineoplastic agents' extravasation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Combined use of covered stent and flow diversion to seal iatrogenic carotid injury with vessel preservation during transsphenoidal endoscopic resection of clival tumor.

PubMed

Shakir, Hakeem J; Garson, Alex D; Sorkin, Grant C; Mokin, Maxim; Eller, Jorge L; Dumont, Travis M; Popat, Saurin R; Leonardo, Jody; Siddiqui, Adnan H

2014-01-01

Transsphenoidal tumor resection can lead to internal carotid artery (ICA) injury. Vascular disruption is often treated with emergent vessel deconstruction, incurring complications in a subset of patients with poor collateral circulation and resulting in minor and major ischemic strokes. We attempted a novel approach combining a covered stent graft (Jostent) and two flow diverter stents [Pipeline embolization devices (PEDs)] to treat active extravasation from a disrupted right ICA that was the result of a transsphenoidal surgery complication. This disruption occurred during clival tumor surgery and required immediate sphenoidal sinus packing. Emergent angiography revealed continued petrous carotid artery extravasation, warranting emergent vessel repair or deconstruction for treatment. To preserve the vessel, we utilized a covered Jostent. Due to tortuosity and lack of optimal wall apposition, there was reduced, yet persistent extravasation from an endoleak after Jostent deployment that failed to resolve despite multiple angioplasties. Therefore, we used PEDs to divert the flow. Flow diversion relieved the extravasation. The patient remained neurologically intact post-procedure. This case demonstrates successful combined use of a covered stent and flow diverters to treat acute vascular injury resulting from transsphenoidal surgery. However, concerns remain, including the requirement of dual antiplatelet agents increasing postoperative bleeding risks, stent-related thromboembolic events, and delayed in-stent restenosis rates.

The involvement of sympathetic nerves in plasma extravasation induced by prostaglandin E2 and substance P.

PubMed

Mathison, R; Davison, J S

1994-05-02

The effects of intravenous injection of prostaglandin E2 (PGE2), substance P (SP) and a metabolically stable SP analogue, [pGlu5,Me-Phe8,Sar9]-SP (5-11) on plasma extravasation of albumin in the rat after blockade of prostaglandin synthesis with indomethacin or chemical sympathectomy with guanethidine were studied. Blood pressure was decreased by all agonists, but only the hypotensive effects of SP were enhanced by pretreatment with indomethacin and guanethidine. The increase in plasma extravasation induced by PGE2 in the tongue, skin and lungs was blocked by both guanethidine and indomethacin. Pretreatment of the rats with guanethidine or indomethacin increased extravasation induced by SP in the tongue-tip, dorsal skin and foot, but decreased the enhanced permeability in the pinna, and did not alter the actions of the peptide in other tissues. In contrast, both guanethidine and indomethacin pretreatment increased vascular permeability responses to [pGlu5,Me-Phe8,Sar9]-SP (5-11) administration in 9 and 14 of 16 tissues examined, respectively. Thus, intact sympathetic nerves and functional cycloxygenase activity exert inhibitory constraints on the vascular permeability effects of intravenously administered SP or its analogue. On the other hand the integrity of the sympathetic nerves and prostaglandin synthesis are required for PGE2-induced increases in vascular leak.

Semisolid formulations containing dimethyl sulfoxide and alpha-tocopherol for the treatment of extravasation of antiblastic agents.

PubMed

Casiraghi, Antonella; Ardovino, Paola; Minghetti, Paola; Botta, Cinzia; Gattini, Arrigo; Montanari, Luisa

2007-07-01

The topical treatment with dimethyl sulfoxide (DMSO) and/or alpha-tocopherol (alpha-T) is widely used in order to prevent the local complications of extravasation of cytostatic drugs and protect patients against skin ulceration. Till now, DMSO and alpha-T have been mainly used in solution. The goal of this study was to formulate semisolid preparations for cutaneous application differing in the hydrophilic and lipophilic properties and containing DMSO and alpha-T in combination. With respect to solutions, the use of semisolid preparations containing DMSO and alpha-T could be advantageous in patients having extravasation as DMSO and alpha-T can remain in contact with the skin over an extended period of time. As a consequence, the action of the active principles can be limited specifically on the injured skin area, reducing the cutaneous irritative effects of DMSO. The following types of semisolid formulations containing 50% m/m DMSO and 2.5% m/m alpha-T were prepared: hydrophilic ointment, o/w emulsion, hydrophilic gel and lipophilic gel. The ex vivo skin permeation of DMSO and alpha-T was evaluated by using modified Franz's diffusion cells and human stratum corneum and epidermis (SCE) as a membrane. The permeated and retained amounts of DMSO and alpha-T were determined. The oleogel preparation, the hydrophilic gel and the o/w emulsion were uniform in colour and aspect, without any evidences of phase separation over the period of the study. Hydrophilic ointments were discarded as they showed phase separation after 12 h. All formulations had a different behaviour in terms of skin permeability. In particular, hydrogel and o/w emulsion showed the best control on the drug release considering the interactions of the vehicle components with the SCE and the drugs partition between the vehicle and the SCE. The DMSO permeated amount after 24 h was 4.1 mg/cm(2) for hydrogel and 2.5 mg/cm(2) for emulsion while the permeated amount of pure DMSO after 24 h was 47.5 mg/cm(2). Therefore, aiming to reduce side effects after the topical application of the antidotes DMSO and alpha-T, these results suggested that hydrogel and o/w emulsion could be considered the most promising formulations for further clinical evaluations in managing of extravasation of anthracyclines.

Rac1-Regulated Endothelial Radiation Response Stimulates Extravasation and Metastasis That Can Be Blocked by HMG-CoA Reductase Inhibitors

PubMed Central

Hamalukic, Melanie; Huelsenbeck, Johannes; Schad, Arno; Wirtz, Stefan; Kaina, Bernd; Fritz, Gerhard

2011-01-01

Radiotherapy (RT) plays a key role in cancer treatment. Although the benefit of ionizing radiation (IR) is well established, some findings raise the possibility that irradiation of the primary tumor not only triggers a killing response but also increases the metastatic potential of surviving tumor cells. Here we addressed the question of whether irradiation of normal cells outside of the primary tumor augments metastasis by stimulating the extravasation of circulating tumor cells. We show that IR exposure of human endothelial cells (EC), tumor cells (TC) or both increases TC-EC adhesion in vitro. IR-stimulated TC-EC adhesion was blocked by the HMG-CoA reductase inhibitor lovastatin. Glycyrrhizic acid from liquorice root, which acts as a Sialyl-Lewis X mimetic drug, and the Rac1 inhibitor NSC23766 also reduced TC-EC adhesion. To examine the in vivo relevance of these findings, tumorigenic cells were injected into the tail vein of immunodeficient mice followed by total body irradiation (TBI). The data obtained show that TBI dramatically enhances tumor cell extravasation and lung metastasis. This pro-metastatic radiation effect was blocked by pre-treating mice with lovastatin, glycyrrhizic acid or NSC23766. TBI of mice prior to tumor cell transplantation also stimulated metastasis, which was again blocked by lovastatin. The data point to a pro-metastatic trans-effect of RT, which likely rests on the endothelial radiation response promoting the extravasation of circulating tumor cells. Administration of the widely used lipid-lowering drug lovastatin prior to irradiation counteracts this process, likely by suppressing Rac1-regulated E-selectin expression following irradiation. The data support the concern that radiation exposure might increase the extravasation of circulating tumor cells and recommend co-administration of lipid-lowering drugs to avoid this adverse effect of ionizing radiation. PMID:22039482

A Microfluidic System for the Investigation of Tumor Cell Extravasation.

PubMed

Kühlbach, Claudia; da Luz, Sabrina; Baganz, Frank; Hass, Volker C; Mueller, Margareta M

2018-05-23

Metastatic dissemination of cancer cells is a very complex process. It includes the intravasation of cells into the metastatic pathways, their passive distribution within the blood or lymph flow, and their extravasation into the surrounding tissue. Crucial steps during extravasation are the adhesion of the tumor cells to the endothelium and their transendothelial migration. However, the molecular mechanisms that are underlying this process are still not fully understood. Novel three dimensional (3D) models for research on the metastatic cascade include the use of microfluidic devices. Different from two dimensional (2D) models, these devices take cell⁻cell, structural, and mechanical interactions into account. Here we introduce a new microfluidic device in order to study tumor extravasation. The device consists of three different parts, containing two microfluidic channels and a porous membrane sandwiched in between them. A smaller channel together with the membrane represents the vessel equivalent and is seeded separately with primary endothelial cells (EC) that are isolated from the lung artery. The second channel acts as reservoir to collect the migrated tumor cells. In contrast to many other systems, this device does not need an additional coating to allow EC growth, as the primary EC that is used produces their own basement membrane. VE-Cadherin, an endothelial adherence junction protein, was expressed in regular localization, which indicates a tight barrier function and cell⁻cell connections of the endothelium. The EC in the device showed in vivo-like behavior under flow conditions. The GFP-transfected tumor cells that were introduced were of epithelial or mesenchymal origin and could be observed by live cell imaging, which indicates tightly adherent tumor cells to the endothelial lining under different flow conditions. These results suggest that the new device can be used for research on molecular requirements, conditions, and mechanism of extravasation and its inhibition.

Quantitative Analysis of Human Cancer Cell Extravasation Using Intravital Imaging.

PubMed

Willetts, Lian; Bond, David; Stoletov, Konstantin; Lewis, John D

2016-01-01

Metastasis, or the spread of cancer cells from a primary tumor to distant sites, is the leading cause of cancer-associated death. Metastasis is a complex multi-step process comprised of invasion, intravasation, survival in circulation, extravasation, and formation of metastatic colonies. Currently, in vitro assays are limited in their ability to investigate these intricate processes and do not faithfully reflect metastasis as it occurs in vivo. Traditional in vivo models of metastasis are limited by their ability to visualize the seemingly sporadic behavior of where and when cancer cells spread (Reymond et al., Nat Rev Cancer 13:858-870, 2013). The avian embryo model of metastasis is a powerful platform to study many of the critical steps in the metastatic cascade including the migration, extravasation, and invasion of human cancer cells in vivo (Sung et al., Nat Commun 6:7164, 2015; Leong et al., Cell Rep 8, 1558-1570, 2014; Kain et al., Dev Dyn 243:216-28, 2014; Leong et al., Nat Protoc 5:1406-17, 2010; Zijlstra et al., Cancer Cell 13:221-234, 2008; Palmer et al., J Vis Exp 51:2815, 2011). The chicken chorioallantoic membrane (CAM) is a readily accessible and well-vascularized tissue that surrounds the developing embryo. When the chicken embryo is grown in a shell-less, ex ovo environment, the nearly transparent CAM provides an ideal environment for high-resolution fluorescent microcopy approaches. In this model, the embryonic chicken vasculature and labeled cancer cells can be visualized simultaneously to investigate specific steps in the metastatic cascade including extravasation. When combined with the proper image analysis tools, the ex ovo chicken embryo model offers a cost-effective and high-throughput platform for the quantitative analysis of tumor cell metastasis in a physiologically relevant in vivo setting. Here we discuss detailed procedures to quantify cancer cell extravasation in the shell-less chicken embryo model with advanced fluorescence microscopy techniques.

Extravasal occlusion of large vessels with titanic clips: efficiency, indications, and contraindications.

PubMed

Vasilenko, Yu V; Kim, A I; Kotov, S A

2002-11-01

The mechanism of extravasal occlusion of blood vessels with titanic clips "Atrauclip" and "Ligaclip extra" was studied in order to reveal indications and contraindications to their use. Occlusion with the clips of both types was ineffective in vessels with a diameter of >7.0 mm. Arteritis or the presence of an intravascular occlusion facility in the vessel were also the contraindications for clip occlusion. In overcases the procedure of occlusion with titanic clips was efficient and atraumatic.

Development of an Evidence-Based List of Noncytotoxic Vesicant Medications and Solutions.

PubMed

Gorski, Lisa A; Stranz, Marc; Cook, Lynda S; Joseph, James M; Kokotis, Kathy; Sabatino-Holmes, Pam; Van Gosen, Lori

Infiltration of a vesicant medication, defined as extravasation, may result in significant patient injuries. The first step in preventing extravasation is the identification and recognition of vesicant medications and solutions. Because there is no list of noncytotoxic vesicants as established by a professional organization, the Infusion Nurses Society, as the global authority in infusion nursing, identified the need to address this gap. A task force was formed for the purpose of creating an evidence-based list of noncytotoxic vesicant medications and solutions.

Hyperacute perimesencephalic subarachnoid hemorrhage: demonstration of blood extravasation with MRI.

PubMed

Küker, W; Thiex, R; Block, F

1999-01-01

Perimesencephalic subarachnoid hemorrhage (SAH) is a benign subtype of SAH without known vascular pathology. We report a case of current subarachnoid bleeding in the vicinity of the basilar artery. The patient was on anticoagulation medication and had sustained a head injury 2 days earlier. The bleeding was documented by contrast agent extravasation in MRI. Because of the isointensity of hyperacute blood to CSF in conventional T2 sequences, FLAIR images are mandatory for diagnosis in the hyperacute state.

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

increased PhScN potency as a result of preventing endoproteolytic degradation. Finally, the in vivo lung extravasation and colonization data, as well as...successful colonization are late stages in breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony...Award Number: TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma

Design of a dynamic optical tissue phantom to model extravasation pharmacokinetics

NASA Astrophysics Data System (ADS)

Zhang, Jane Y.; Ergin, Aysegul; Andken, Kerry Lee; Sheng, Chao; Bigio, Irving J.

2010-02-01

We describe an optical tissue phantom that enables the simulation of drug extravasation from microvessels and validates computational compartmental models of drug delivery. The phantom consists of a microdialysis tubing bundle to simulate the permeable blood vessels, immersed in either an aqueous suspension of titanium dioxide (TiO2) or a TiO2 mixed agarose scattering medium. Drug administration is represented by a dye circulated through this porous microdialysis tubing bundle. Optical pharmacokinetic (OP) methods are used to measure changes in the absorption coefficient of the scattering medium due to the arrival and diffusion of the dye. We have established particle sizedependent concentration profiles over time of phantom drug delivery by intravenous (IV) and intra-arterial (IA) routes. Additionally, pharmacokinetic compartmental models are implemented in computer simulations for the conditions studied within the phantom. The simulated concentration-time profiles agree well with measurements from the phantom. The results are encouraging for future optical pharmacokinetic method development, both physical and computational, to understand drug extravasation under various physiological conditions.

Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

PubMed Central

Schnoor, Michael; Alcaide, Pilar; Voisin, Mathieu-Benoit; van Buul, Jaap D.

2015-01-01

Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers. PMID:26568666

Platelets Guide Leukocytes to Their Sites of Extravasation

PubMed Central

Puhr-Westerheide, Daniel; Pörnbacher, Michaela; Lauber, Kirsten; Krombach, Fritz; Reichel, Christoph Andreas

2016-01-01

Effective immune responses require the directed migration of leukocytes from the vasculature to the site of injury or infection. How immune cells “find” their site of extravasation remains largely obscure. Here, we identified a previously unrecognized role of platelets as pathfinders guiding leukocytes to their exit points in the microvasculature: upon onset of inflammation, circulating platelets were found to immediately adhere at distinct sites in venular microvessels enabling these cellular blood components to capture neutrophils and, in turn, inflammatory monocytes via CD40-CD40L-dependent interactions. In this cellular crosstalk, ligation of PSGL-1 by P-selectin leads to ERK1/2 MAPK-dependent conformational changes of leukocyte integrins, which promote the successive extravasation of neutrophils and monocytes to the perivascular tissue. Conversely, blockade of this cellular partnership resulted in misguided, inefficient leukocyte responses. Our experimental data uncover a platelet-directed, spatiotemporally organized, multicellular crosstalk that is essential for effective trafficking of leukocytes to the site of inflammation. PMID:27152726

Preventing the activation or cycling of the Rap1 GTPase alters adhesion and cytoskeletal dynamics and blocks metastatic melanoma cell extravasation into the lungs.

PubMed

Freeman, Spencer A; McLeod, Sarah J; Dukowski, Janet; Austin, Pamela; Lee, Crystal C Y; Millen-Martin, Brandie; Kubes, Paul; McCafferty, Donna-Marie; Gold, Michael R; Roskelley, Calvin D

2010-06-01

The Rap1 GTPase is a master regulator of cell adhesion, polarity, and migration. We show that both blocking Rap1 activation and expressing a constitutively active form of Rap1 reduced the ability of B16F1 melanoma cells to extravasate from the microvasculature and form metastatic lesions in the lungs. This correlated with a decreased ability of the tumor cells to undergo transendothelial migration (TEM) in vitro and form dynamic, F-actin-rich pseudopodia that penetrate capillary endothelial walls in vivo. Using multiple tumor cell lines, we show that the inability to form these membrane protrusions, which likely promote TEM and extravasation, can be explained by altered adhesion dynamics and impaired cell polarization that result when Rap1 activation or cycling is perturbed. Thus, targeting Rap1 could be a useful approach for reducing the metastatic dissemination of tumor cells that undergo active TEM. Copyright 2010 AACR.

Osthole Enhances the Therapeutic Efficiency of Stem Cell Transplantation in Neuroendoscopy Caused Traumatic Brain Injury.

PubMed

Tao, Zhen-Yu; Gao, Peng; Yan, Yu-Hui; Li, Hong-Yan; Song, Jie; Yang, Jing-Xian

2017-01-01

Neuroendoscopy processes can cause severe traumatic brain injury. Existing therapeutic methods, such as neural stem cell transplantation and osthole have not been proven effective. Therefore, there is an emerging need on the development of new techniques for the treatment of brain injuries. In this study we propose to combine the above stem cell based methods and then evaluate the efficiency and accuracy of the new method. Mice were randomly divided into four groups: group 1 (brain injury alone); group 2 (osthole); group 3 (stem cell transplantation); and group 4 (osthole combined with stem cell transplantation). We carried out water maze task to exam spatial memory. Immunocytochemistry was used to test the inflammatory condition of each group, and the differentiation of stem cells. To evaluate the condition of the damaged blood brain barrier restore, we detect the Evans blue (EB) extravasation across the blood brain barrier. The result shows that osthole and stem cell transplantation combined therapeutic method has a potent effect on improving the spatial memory. This combined method was more effective on inhibiting inflammation and preventing neuronal degeneration than the single treated ones. In addition, there was a distinct decline of EB extravasation in the combined treatment groups, which was not observed in single treatment groups. Most importantly, the combined usage of osthole and stem cell transplantation provide a better treatment for the traumatic brain injury caused by neuroendoscopy. The collective evidence indicates osthole combined with neural stem cell transplantation is superior than either method alone for the treatment of traumatic brain injury caused by neuroendoscopy.

Use of computed tomography findings and contrast extravasation in predicting the need for embolization with pelvic fractures.

PubMed

Bozeman, Matthew C; Cannon, Robert M; Trombold, John M; Smith, Jason W; Franklin, Glen A; Miller, Frank B; Richardson, J David; Harbrecht, Brian G

2012-08-01

Transarterial embolization (AE) can be a lifesaving procedure for severe hemorrhage associated with pelvic fractures. The purpose of this study was to identify demographic and radiographic findings that predict the need for embolization. We performed a retrospective review of all patients with at least one pelvic fracture and admission to the intensive care unit over a 35-month period. Computed tomography (CT) and pelvic radiographs were reviewed. Patient demographics, outcomes, time to angiography, and whether or not embolization was performed were determined. Statistical analysis was used to determine factors associated with the need for AE. Of the 327 total patients with pelvic fractures, 317 underwent CT scanning. Forty-four patients (13.5%) underwent angiography and 25 (7.6%) required therapeutic embolization. There were 39 total deaths (11.6%) with five deaths related to pelvic hemorrhage (1.5%). Multivariate analysis revealed that age older than 55 years (odds ratio [OR], 1.06; P < 0.001), systolic blood pressure less than 90 mmHg in the emergency department (OR, 11.64; P = 0.0008), and CT extravasation (OR, 147.152; P < 0.0001) were significantly associated with the need for embolization. Contrast extravasation was not present in 25 per cent of patients requiring therapeutic AE. The presence of contrast extravasation is highly associated with the need for pelvic embolization in patients with pelvic fractures, but its absence does not exclude the need for pelvic angiography.

A novel lymphoid enhancer-binding factor 1-cytoglobin axis promotes extravasation of osteosarcoma cells into the lungs.

PubMed

Pongsuchart, Mongkol; Kuchimaru, Takahiro; Yonezawa, Sakiko; Tran, Diem Thi Phuong; Kha, Nguyen The; Hoang, Ngoc Thi Hong; Kadonosono, Tetsuya; Kizaka-Kondoh, Shinae

2018-06-21

Lung metastasis is a major cause of mortality in patients with osteosarcoma (OS). A better understanding of the molecular mechanism of OS lung metastasis may facilitate development of new therapeutic strategies to prevent the metastasis. We have established high- and low-metastatic sublines (LM8-H and LM8-L respectively) from Dunn OS cell line LM8 by using in vivo image-guided screening. Among the genes whose expression was significantly increased in LM8-H compared to LM8-L, the transcription factor lymphoid enhancer-binding factor 1 (LEF1) was identified as a factor that promotes LM8-H cell extravasation into the lungs. To identify downstream effectors of LEF1 that are involved in OS lung metastasis, 13 genes were selected based on the LM8 microarray data and genome-wide meta-analysis of a public database for OS patients. Among them, the cytoglobin (Cygb) gene was identified as a key effector in promoting OS extravasation into the lungs. CYGB overexpression increased the extravasation ability of LM8-L cells, whereas knocking out the Cygb gene in LM8-H cells reduced this ability. Our results uncovered a novel LEF1-CYGB axis in OS lung metastasis and may open a new avenue for developing therapeutic strategies to prevent OS lung metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Increased Liposome Extravasation in Selected Tissues: Effect of Substance P

NASA Astrophysics Data System (ADS)

Rosenecker, Joseph; Zhang, Weiming; Hong, Keelung; Lausier, James; Geppetti, Pierangelo; Yoshihara, Shigemi; Papahadjopoulos, Demetrios; Nadel, Jay A.

1996-07-01

We have used a pharmacologic mediator to open intercellular connections in selected vessels to allow liposomes to escape from the blood stream and to extravasate into tissues that have appropriate receptors. We have examined the effects of substance P (SP), a peptide known to increase vascular permeability in selected tissues, such as trachea, esophagus, and urinary bladder in rats. We used quantitative fluorescence analysis of tissues to measure two fluorescent markers, one attached to the lipid (rhodamine-phosphatidylethanolamine) and another, doxorubicin (an antitumor drug), encapsulated within the aqueous interior. We have also examined the deposition of liposomes microscopically by the use of encapsulated colloidal gold and silver enhancement. Analysis of the biochemical and morphological observations indicate the following: (i) Injection of SP produces a striking increase in both liposome labels, but only in tissues that possess receptors for SP in postcapillary venules; (ii) liposome material in these tissues has extravasated and is found extracellularly near a variety of cells beyond the endothelial layer over the first few hours; (iii) 24 h following injection of liposomes and SP, liposome material is found in these tissues, localized intracellularly in both endothelial cells and macrophages. We propose that appropriate application of tissue-specific mediators can result in liposome extravasation deep within tissues that normally do not take up significant amounts of liposomes from the blood. Such liposomes are able to carry a variety of pharmacological agents that can be released locally within selected target tissues for therapeutic purposes.

Study of non-uniform nanoparticle liposome extravasation in tumour.

PubMed

Liu, P; Zhang, A; Xu, Y; Xu, L X

2005-05-01

The effect of hyperthermia on the nanoparticle extravasation in different tumour regions was investigated in real time using confocal laser scanning microscopy. Murine mammary carcinoma 4T1 was implanted in the nude mice dorsal skin-fold window chamber. Tumour angiogenesis was observed through the window chamber on days 4, 7, 8 and 10 after the implantation. In 10 days, the tumour became 1-2 mm in diameter and 150 microm thick. Most vessels were found to be <15 microm in diameter. Histological examination showed that there were fewer vessels in a more ordered branching pattern inside the tumour than in the tumour periphery. After hyperthermia at 42 degrees C for 1 h, numerous erythrocytes were found in the peripheral region. Extravasation of rhodamine-labelled 100 nm nanoparticles in different tumour regions under both normal and hyperthermic conditions (34 and 42 degrees C) was quantified using confocal fluorescence microscopy. The relative fluorescence intensity hardly changed in tissue at 34 degrees C, but increased by the local hyperthermia at 42 degrees C. In particular, the relative intensity in the tumour periphery was more than 120 as compared to 40 in the tumour centre, after 1 h hyperthermia. Results showed that the thermally induced liposome nanoparticle extravasation was heterogeneous in tumour, owing to the non-uniform distribution of tumour vasculature. Further, the degree of vascular damage was found to be more severe in the tumour periphery, which is likely due to the high thermal sensitivity of newly formed tumour vessels in this region.

Chemotherapy drug extravasation in totally implantable venous access port systems: how effective is early surgical lavage?

PubMed

Azaïs, Henri; Bresson, Lucie; Bassil, Alfred; Katdare, Ninad; Merlot, Benjamin; Houpeau, Jean-Louis; El Bedoui, Sophie; Meurant, Jean-Pierre; Tresch, Emmanuelle; Narducci, Fabrice

2015-01-01

Totally implantable venous access port systems (TIVAPS) are a widely used and an essential tool in the efficient delivery of chemotherapy. Chemotherapy drug extravasation (CDE) can have dire consequences and will delay treatment. The purpose of this study is to both clarify the management of CDE and show the effectiveness of early surgical lavage (ESL). Patients who had presented to the Cancer Center of Lille (France) with TIVAPS inserted between January 2004 and April 2013 and CDE had their medical records reviewed retrospectively. Thirty patients and 33 events were analyzed. Implicated agents were vesicants (51.5%), irritants (45.5%) and non-vesicants (3%). Huber needle malpositionning was involved in 27 cases. Surgery was performed in 97% of cases, 87.5% of which were for ESL with 53.1% of the latter requiring TIVAPS extraction. Six patients required a second intervention due to adverse outcomes (severe cases). Vesicants were found to be implicated in four out of six severe cases and oxaliplatin in two others. Extravasated volume was above 50 ml in 80% of cases. Only one patient required a skin graft. CDEs should be managed in specialized centers. ESL allows for limited tissue contact of the chemotherapy drug whilst using a simple, widely accessible technique. The two main factors that correlate with adverse outcome seem to be the nature of the implicated agent (vesicants) and the extravasated volume (above 50 ml) leading to worse outcomes. Oxaliplatin should be considered as a vesicant.

Human bone marrow mesenchymal stem cells for retinal vascular injury.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

2017-09-01

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

The pattern of early lung parenchymal and air space injury following acute blood loss.

PubMed

Younger, J G; Taqi, A S; Jost, P F; Till, G O; Johnson, K J; Stern, S A; Hirschl, R B

1998-07-01

Acute lung injury is a frequent clinical occurrence following blood loss and trauma. The nature of this injury remains poorly understood. To examine the relative parenchymal and intra-alveolar distribution of inflammation in a rat model of hemorrhage and resuscitation. Rats were anesthetized and subjected to hemorrhage followed by resuscitation with shed blood and saline. Myeloperoxidase activity of lung homogenates and cytology of bronchoalveolar lavage fluid were used to measure total lung and intra-alveolar neutrophil invasion. Extravasation of i.v.-administered [125I]-albumin was used to determine total lung and alveolar permeability. Permeability results were analyzed using their base-10 logarithmic transformations. 86 animals were studied. Whole-lung myeloperoxidase activity was increased (control = 0.34 +/- 0.16 units, injured = 0.84 +/- 0.43 units, p < 0.01), while there was no difference in intra-alveolar leukocyte counts (injured = 1.85 +/- 1.30 x 10(5)/mL, control = 2.44 +/- 1.75 x 10(5)/mL, p = 0.40), suggesting that the cellular component of the injury was more severe in the intravascular and interstitial spaces. There was a strong trend toward increased permeability in the interstitial compartment, and a significant increase in permeability in the intra-alveolar compartment (whole-lung permeability: control = -0.27 +/- 0.19 units, injured = 0.10 +/- 0.55 units, p = 0.06; alveolar permeability: control = -2.00 +/- 0.47 units, injured = -1.32 +/- 0.49 units, p < 0.01), suggesting that the loss of integrity to macromolecules was not limited to the interstitium. Hemorrhage and resuscitation resulted in an acute lung injury characterized by extravasation of intravascular protein into both the interstitium and the intra-alveolar space. Neutrophil invasion of the lung was demonstrable only in the interstitial compartment.

Embolization of Isolated Lumbar Artery Injuries in Trauma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sofocleous, Constantinos T., E-mail: constant@pol.net; Hinrichs, Clay R.; Hubbi, Basil

Purpose. The purpose of the study was to evaluate the angiographic findings and results of embolotherapy in the management of lumbar artery trauma. Methods. All patients with lumbar artery injury who underwent angiography and percutaneous embolization in a state trauma center within a 10-year period were retrospectively reviewed. Radiological information and procedural reports were reviewed to assess immediate angiographic findings and embolization results. Long-term clinical outcome was obtained by communication with the trauma physicians as well as with chart review. Results. In a 10-year period, 255 trauma patients underwent abdominal aortography. Eleven of these patients (three women and eight men)more » suffered a lumbar artery injury. Angiography demonstrated active extravasation (in nine) and/or pseudoaneurysm (in four). Successful selective embolization of abnormal vessel(s) was performed in all patients. Coils were used in six patients, particles in one and gelfoam in five patients. Complications included one retroperitoneal abscess, which was treated successfully. One patient returned for embolization of an adjacent lumbar artery due to late pseudoaneurysm formation. Conclusions. In hemodynamically stable patients, selective embolization is a safe and effective method for immediate control of active extravasation, as well as to prevent future hemorrhage from an injured lumbar artery.« less

Data-Driven Discovery of Extravasation Pathway in Circulating Tumor Cells

PubMed Central

Yadavalli, S.; Jayaram, S.; Manda, S. S.; Madugundu, A. K.; Nayakanti, D. S.; Tan, T. Z.; Bhat, R.; Rangarajan, A.; Chatterjee, A.; Gowda, H.; Thiery, J. P.; Kumar, P.

2017-01-01

Circulating tumor cells (CTCs) play a crucial role in cancer dissemination and provide a promising source of blood-based markers. Understanding the spectrum of transcriptional profiles of CTCs and their corresponding regulatory mechanisms will allow for a more robust analysis of CTC phenotypes. The current challenge in CTC research is the acquisition of useful clinical information from the multitude of high-throughput studies. To gain a deeper understanding of CTC heterogeneity and identify genes, pathways and processes that are consistently affected across tumors, we mined the literature for gene expression profiles in CTCs. Through in silico analysis and the integration of CTC-specific genes, we found highly significant biological mechanisms and regulatory processes acting in CTCs across various cancers, with a particular enrichment of the leukocyte extravasation pathway. This pathway appears to play a pivotal role in the migration of CTCs to distant metastatic sites. We find that CTCs from multiple cancers express both epithelial and mesenchymal markers in varying amounts, which is suggestive of dynamic and hybrid states along the epithelial-mesenchymal transition (EMT) spectrum. Targeting the specific molecular nodes to monitor disease and therapeutic control of CTCs in real time will likely improve the clinical management of cancer progression and metastases. PMID:28262832

Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

DTIC Science & Technology

2015-11-01

systemic therapy to prevent breast cancer bone colony progression. Figure 6. Colocalization of Ac-PhscNGGK-Bio with DiI in lung– extravasated SUM149PT cells...breast cancer progression that are ultimately fatal. Hence, prevention of extravasation which leads to colony formation would increase life...1 Award Number: W81XWH-12-1-0097 TITLE: “Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site

Local and systemic tumor immune dynamics

NASA Astrophysics Data System (ADS)

Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

[Extravasation injuries in newborns: our experience about 15 cases].

PubMed

Nandiolo-Anelone, K R; Allah, K C; Cissé, L; Bankolé, S R; Oulaï, M; Aké, A Y L

2014-02-01

Extravasation injuries are common complications that occur during infusion for diagnostic or therapeutic purposes by the peripheral or central venous catheters. In pediatric settings, iatrogenic extravasations are serious. When they are viewed late, they are sources of functional sequelae. The purpose of this study was to report our experience with the management of iatrogenic extravasations for therapeutic purposes. Between January 2010 and December 2012, fifteen newborns were supported for accidents of infusion of the upper and the lower limbs. The male was mostly affected. The mean age was 3.6days, with extremes of one and nine days. The average birth weight was 2900g. The range was 1200g and 3550g. Serum 10 % glucose and calcium chloride were implicated in all cases. The lesions were seen in the late stages III in six cases and IV in nine cases. The upper limbs were frequently affected. Nine lesions were in the upper limbs and six in the lower limbs. The dorsal surfaces, feet and hands were frequently affected in six and five cases, respectively. Two lesions were in the anterior aspect of the forearm and elbow. Elbows lesions were circular and realized a tourniquet effect. Treatment was conservative in eleven cases: five pro-inflammatory fatty dressings and six alcoholic dressings. The surgery was delayed in four cases. It combined excision-full thickness skin graft, excision-dressing-thin skin grafting, debridement and two-full thickness skin graft for retractable wrist scars. Two deaths were related to associate pathologies. One patient was lost for follow-up. Our results were satisfactory in functional, aesthetic and psychological aspects. Extravasation injuries are serious iatrogenic lesions. If the lesions are seen at an early stage in usual circumstances, in extreme exercise, they are seen late, sometimes at the stage of functional, psychological and cosmetic sequelae. The difficulty of the therapeutic management of these lesions requires prevention through the development of protocols and the permanent training of nursing staff for an efficient practice of infusion. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

A murine experimental anthracycline extravasation model: pathology and study of the involvement of topoisomerase II alpha and iron in the mechanism of tissue damage.

PubMed

Thougaard, Annemette V; Langer, Seppo W; Hainau, Bo; Grauslund, Morten; Juhl, Birgitte Ravn; Jensen, Peter Buhl; Sehested, Maxwell

2010-02-28

The bisdioxopiperazine topoisomerase II catalytic inhibitor dexrazoxane has successfully been introduced into the clinic as an antidote to accidental anthracycline extravasation based on our preclinical mouse studies. The histology of this mouse extravasation model was investigated and found to be similar to findings in humans: massive necrosis in the subcutis, dermis and epidermis followed by sequestration and healing with granulation tissue, and a graft-versus-host-like reaction with hyperkeratotic and acanthotic keratinocytes, occasional apoptoses, epidermal invasion by lymphocytes and healing with dense dermal connective tissue. The extension of this fibrosis was quantified, and dexrazoxane intervention resulted in a statistically significant decrease in fibrosis extension, as also observed in the clinic. Several mechanisms have been proposed in anthracycline extravasation cytotoxicity, and we tested two major hypotheses: (1) interaction with topoisomerase II alpha and (2) the formation of tissue damaging reactive oxygen species following redox cycling of an anthracycline Fe(2+) complex. Dexrazoxane could minimise skin damage via both mechanisms, as it stops the catalytic activity of topoisomerase II alpha and thereby prevents access of anthracycline to the enzyme and thus cytotoxicity, and also acts as a strong iron chelator following opening of its two bisdioxopiperazine rings. Using the model of extravasation in a dexrazoxane-resistant transgenic mouse with a heterozygous mutation in the topoisomerase II alpha gene (Top2a(Y165S/+)), we found that dexrazoxane provided a protection against anthracycline-induced skin wounds that was indistinguishable from that found in wildtype mice. Thus, interaction with topoisomerase II alpha is not central in the pathogenesis of anthracycline-induced skin damage. In contrast to dexrazoxane, the iron-chelating bisdioxopiperazine ICRF-161 do not inhibit the catalytic cycle of topoisomerase II alpha. This compound was used to isolate and test the importance of iron in the wound pathogenesis. ICRF-161 was found ineffective in the treatment of anthracycline-induced skin damage, suggesting that iron does not play a dominant role in the genesis of wounds. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl.

PubMed

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal-bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER.

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl

PubMed Central

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal–bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER. PMID:29867575

Pigment Epithelium-Derived Factor Blocks Tumor Extravasation by Suppressing Amoeboid Morphology and Mesenchymal Proteolysis12

PubMed Central

Ladhani, Omar; Sánchez-Martinez, Cristina; Orgaz, Jose L; Jimenez, Benilde; Volpert, Olga V

2011-01-01

Metastatic melanoma cells are highly adaptable to their in vivo microenvironment and can switch between protease-dependent mesenchymal and protease-independent amoeboid invasion to facilitate metastasis. Such adaptability can be visualized in vitro, when cells are cultured in conditions that recapitulate three-dimensional microenvironments. Using thick collagen layers in cell culture and in vivo extravasation assays, we found that pigment epithelium-derived factor (PEDF) suppressed lung extravasation of aggressive melanoma by coordinated regulation of cell shape and proteolysis. In cells grown on a thick collagen bed, PEDF overexpression and exogenous PEDF blocked the rapidly invasive, rounded morphology, and promoted an elongated, mesenchymal-like phenotype associated with reduced invasion. These changes in cell shape depended on decreased RhoA and increased Rac1 activation and were mediated by the up-regulation of Rac1-GEF, DOCK3 and down-regulation of Rac1-GAP, ARHGAP22. Surprisingly, we found that PEDF overexpression also blocked the trafficking of membrane-tethered, MT1-MMP to the cell surface through RhoA inhibition and Rac1 activation. In vivo, knockdown of Rac1 and DOCK3 or overexpression of MT1-MMP was sufficient to reverse the inhibitory effect of PEDF on extravasation. Using functional studies, we demonstrated that PEDF suppressed the rounded morphology and MT1-MMP surface localization through its antiangiongenic, 34-mer epitope and the recently identified PEDF receptor candidate, PNPLA2. Our findings unveil the coordinated regulation of cell shape and proteolysis and identify an unknown mechanism for PEDF's antimetastatic activity. PMID:21750657

Involvement of tachykinin receptors in Clostridium perfringens beta-toxin-induced plasma extravasation

PubMed Central

Nagahama, Masahiro; Morimitsu, Shinsuke; Kihara, Atsushi; Akita, Masahiko; Setsu, Koujun; Sakurai, Jun

2003-01-01

Clostridium perfringens beta-toxin causes dermonecrosis and oedema in the dorsal skin of animals. In the present study, we investigated the mechanisms of oedema induced by the toxin. The toxin induced plasma extravasation in the dorsal skin of Balb/c mice. The extravasation was significantly inhibited by diphenhydramine, a histamine 1 receptor antagonist. However, the toxin did not cause the release of histamine from mouse mastocytoma cells. Tachykinin NK1 receptor antagonists, [D-Pro2, D-Trp7,9]-SP, [D-Pro4, D-Trp7,9]-SP and spantide, inhibited the toxin-induced leakage in a dose-dependent manner. Furthermore, the non-peptide tachykinin NK1 receptor antagonist, SR140333, markedly inhibited the toxin-induced leakage. The leakage induced by the toxin was markedly reduced in capsaicin-pretreated mouse skin but the leakage was not affected by systemic pretreatment with a calcitonin gene-related peptide receptor antagonist (CGRP8-37). The toxin-induced leakage was significantly inhibited by the N-type Ca2+ channel blocker, ω-conotoxin MVIIA, and the bradykinin B2 receptor antagonist, HOE140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin), but was not affected by the selective L-type Ca2+ channel blocker, verapamil, the P-type Ca2+ channel blocker, ω-agatoxin IVA, tetrodotoxin (TTX), the TTX-resistant Na+ channel blocker, carbamazepine, or the sensory nerve conduction blocker, lignocaine. These results suggest that plasma extravasation induced by beta-toxin in mouse skin is mediated via a mechanism involving tachykinin NK1 receptors. PMID:12522069

Contrast-enhanced ultrasound imaging of active bleeding associated with hepatic and splenic trauma.

PubMed

Lv, F; Tang, J; Luo, Y; Li, Z; Meng, X; Zhu, Z; Li, T

2011-10-01

The aim of this study was to evaluate contrast-enhanced ultrasound (CEUS) imaging of active bleeding from hepatic and splenic trauma. Three hundred and ninety-two patients with liver or/and spleen trauma (179 liver and 217 spleen injuries), who underwent CEUS examinations following contrast-enhanced computed tomography (CT), were enrolled in this retrospective study over a period of >4 years. CEUS detected contrast medium extravasation or pooling in 16% (63/396) of liver or spleen lesions in 61 patients, which was confirmed by contrast-enhanced CT. Special attention was paid to observing the presence, location, and characteristics of the extravasated or pooled contrast medium. The CEUS detection rate for active bleeding was not different from that of contrast-enhanced CT (p=0.333). Information from surgery, minimally invasive treatment and conservative treatment was used as reference standard, and the sensitivities of the two techniques were not different (p=0.122). Of 63 lesions in 61 patients, CEUS showed that 74.6% (47/63) (21 liver lesions and 26 spleen lesions) presented contrast medium extravasation or pooling, both in the organ and out the capsule, in 14.3% (9/63) and only outside the capsule in 11.1% (7/63). CEUS imaging of active bleeding from hepatic and splenic trauma presented various characteristics, and the sizes and shapes of the active bleeding due to contrast medium extravasation or pooling were variable. CEUS can show the active bleeding associated with hepatic and splenic trauma with various imaging characteristics, thus making it possible to diagnose active bleeding using CEUS.

PAF involvement in dermal extravasation in the reverse passive Arthus reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deacon, R.W.; Melden, M.K.; Saunders, R.N.

The reverse passive erthus reaction (RPAR) is characterized by PMN infiltration, increased vascular permeability leading to plasma extravasation and vessel damage. In the skin RPAR is an inflammatory response initiated by deposition of immune complexes and attributed to complement activation. As PAF can elicit similar dermal reactions, they examined the PAF antagonist SRI 63-072 in the RPAR. Guinea pigs were given an i.v. injection of /sup 125/I-BSA (Ag-20 mg/kg with 20 mg/kg Evan's blue as a permeability tracer), followed by intradermal (i.d.) injections (0.1 ml/site) of anti-BSA antibodies (Ab). After 30 min, dermal sites (2 cm diam.) were removed, countedmore » and the ..mu..l plasma/site (over background counts) calculated from plasma radioactivity measurements. The plasma leakage (..mu..l plasma/site) was dose-dependent upon Ab dose (6-200 ..mu..g/site). At the ultrastructural level, the presence of neutrophils and eosinophils were observed in the extravascular spaces. The luminal endothelium exhibited cytotoxic characteristics and loss of junctional integrity. SRI 63-072 exhibited 50% maximal inhibition when given i.d. with the Ab (0.1 ..mu..g/site) but only 5-10% when given at 3.0 mg/kg i.v. with Ag. No further inhibition of dermal extravasation was observed using SRI 63-441, a competitive receptor antagonist with 3-30 fold the in vivo potency of SRI 63-072. As dermal extravasation in RPAR is only partially inhibited by a PAF antagonist, it appears that other vasoactive mediators, possibly histamine, may be influencing vessel permeability as well.« less

Continuous thermographic observation may predict extravasation in chemotherapy-treated patients.

PubMed

Oya, Maiko; Murayama, Ryoko; Oe, Makoto; Yabunaka, Koichi; Tanabe, Hidenori; Takahashi, Toshiaki; Matsui, Yuko; Otomo, Eiko; Komiyama, Chieko; Sanada, Hiromi

2017-06-01

Extravasation, or leakage of vesicant drugs into subcutaneous tissues, causes serious complications such as induration and necrosis in chemotherapy-treated patients. As macroscopic observation may overlook symptoms during infusion, we focused on skin temperature changes at puncture sites and studied thermographic patterns related to induration or necrosis caused by extravasation. Outpatients undergoing chemotherapy using peripheral intravenous catheters were enrolled in this prospective observational study. We filmed and classified infrared thermography movies of puncture sites during infusion; ultrasonography was also utilized at puncture sites to observe the subcutaneous condition. Multiple logistic regression analysis was performed to examine the association of thermographic patterns with induration or necrosis observed on the next chemotherapy day. Differences in patient characteristics, puncture sites, and infusions were analyzed by Mann-Whitney's U test and Fisher's exact test according to thermographic patterns. Eight patients developed induration among 74 observations in 62 patients. Among six thermographic patterns, a fan-shaped lower temperature area gradually spreading from the puncture site (fan at puncture site) was significantly associated with induration. Ultrasonography revealed that catheters of patients with fan at puncture site remained in the vein at the end of infusion, indicating that the infusion probably leaked from the puncture site. Patients with fan at puncture site had no significant differences in characteristics and infusion conditions compared with those with the other five thermographic patterns. We determined that fan at puncture site was related to induration caused by extravasation. Continuous thermographic observation may enable us to predict adverse events of chemotherapy. Copyright © 2017. Published by Elsevier Ltd.

Assessment of a topical product based on a mixture of polysulfated galactosaminoglycan in the topical treatment of postoperative blood extravasation (ecchymosis-hematoma) in phlebology.

PubMed

Izzo, Marcello; Coscia, Vincenzo

2018-08-01

The onset of bruising in surgery is a frequent event that can be a source of complications and delays in the patient's healing process (pigmentations, fibrosis, etc.). Having the help of an effective topical product that speeds up the resorption of blood extravasation can be an advantage in phlebological surgery and surgery in general. Twenty-three patients both male and female (age range: 30-72 years) were enrolled. Twenty-two of them completed the study, all underwent venous surgery of the lower extremities (invagination stripping of the internal or external saphenous and Muller's ambulatory phlebectomy). The 22 patients were divided into 2 groups of 11 each and in a single blind study received topical daily therapy (every 12 hours) either in the form of a medication cream (active ingredient), or a placebo cream. All patients wore compression one-leg tights immediately after surgery, following measurement of the lower limb (Struva® 35 mmHg, Medi Italia, Zola Predosa, Bologna, Italy). The 30-day observational study was carried out using a standard photographic survey procedure. The topical application of polysulfated galactosaminoglycan showed a significantly higher rate of resorption of blood extravasations than in patients in the single blind study receiving topical therapy with the placebo (Fisher's Exact Test, dichotomous variable outcome, N.=22, with result P=0.0001<0.05). Topical therapy with a mixture of polysulfated galactosaminoglycans provides valid protection in the therapy of blood extravasations in phlebology and general surgery.

Pigment epithelium-derived factor blocks tumor extravasation by suppressing amoeboid morphology and mesenchymal proteolysis.

PubMed

Ladhani, Omar; Sánchez-Martinez, Cristina; Orgaz, Jose L; Jimenez, Benilde; Volpert, Olga V

2011-07-01

Metastatic melanoma cells are highly adaptable to their in vivo microenvironment and can switch between protease-dependent mesenchymal and protease-independent amoeboid invasion to facilitate metastasis. Such adaptability can be visualized in vitro, when cells are cultured in conditions that recapitulate three-dimensional microenvironments. Using thick collagen layers in cell culture and in vivo extravasation assays, we found that pigment epithelium-derived factor (PEDF) suppressed lung extravasation of aggressive melanoma by coordinated regulation of cell shape and proteolysis. In cells grown on a thick collagen bed, PEDF overexpression and exogenous PEDF blocked the rapidly invasive, rounded morphology, and promoted an elongated, mesenchymal-like phenotype associated with reduced invasion. These changes in cell shape depended on decreased RhoA and increased Rac1 activation and were mediated by the up-regulation of Rac1-GEF, DOCK3 and down-regulation of Rac1-GAP, ARHGAP22. Surprisingly, we found that PEDF overexpression also blocked the trafficking of membrane-tethered, MT1-MMP to the cell surface through RhoA inhibition and Rac1 activation. In vivo, knockdown of Rac1 and DOCK3 or overexpression of MT1-MMP was sufficient to reverse the inhibitory effect of PEDF on extravasation. Using functional studies, we demonstrated that PEDF suppressed the rounded morphology and MT1-MMP surface localization through its antiangiongenic, 34-mer epitope and the recently identified PEDF receptor candidate, PNPLA2. Our findings unveil the coordinated regulation of cell shape and proteolysis and identify an unknown mechanism for PEDF's antimetastatic activity.

Anastomotic leakage after colorectal surgery: diagnostic accuracy of CT.

PubMed

Kauv, Paul; Benadjaoud, Samir; Curis, Emmanuel; Boulay-Coletta, Isabelle; Loriau, Jerome; Zins, Marc

2015-12-01

To evaluate the diagnostic accuracy of CT in postoperative colorectal anastomotic leakage (AL). Two independent blinded radiologists reviewed 153 CTs performed for suspected AL within 60 days after surgery in 131 consecutive patients, with (n = 58) or without (n = 95) retrograde contrast enema (RCE). Results were compared to original interpretations. The reference standard was reoperation or consensus (a radiologist and a surgeon) regarding clinical, laboratory, radiological, and follow-up data after medical treatment. AL was confirmed in 34/131 patients. For the two reviewers and original interpretation, sensitivity of CT was 82 %, 87 %, and 71 %, respectively; specificity was 84 %, 84 %, and 92 %. RCE significantly increased the positive predictive value (from 40 % to 88 %, P = 0.0009; 41 % to 92 %, P = 0.0016; and 40 % to 100 %, P = 0.0006). Contrast extravasation was the most sensitive (reviewers, 83 % and 83 %) and specific (97 % and 97 %) sign and was significantly associated with AL by univariate analysis (P < 0.0001 and P < 0.0001). By multivariate analysis with recursive partitioning, CT with RCE was accurate to confirm or rule out AL with contrast extravasation. CT with RCE is accurate for diagnosing postoperative colorectal AL. Contrast extravasation is the most reliable sign. RCE should be performed during CT for suspected AL. • CT accurately diagnosed clinically suspected colorectal AL and showed good interobserver agreement • Contrast extravasation was the most sensitive and specific CT sign • Retrograde contrast enema during CT improved positive predictive value • Retrograde contrast enema decreased false-negative or indeterminate original CT interpretations.

Sensitivity of the Saline Load Test for Traumatic Arthrotomy of the Ankle With Ankle Arthroscopy Simulation.

PubMed

Bohl, Daniel D; Frank, Rachel M; Lee, Simon; Hamid, Kamran S; Holmes, George B; Lin, Johnny; Lee, Simon

2018-06-01

The saline load test has been used to evaluate for traumatic arthrotomy in orthopedics. The purpose of this study was to determine the volume of saline required to detect traumatic arthrotomy of the ankle. Forty-two patients undergoing elective ankle arthroscopy were prospectively enrolled. For each patient, a standard 4-mm anteromedial portal was established. Next, an 18-gauge needle was inserted at the site of the anterolateral portal. Sterile saline was slowly injected through the needle until saline extravasated from the anteromedial portal. Saline volumes at the time of extravasation were recorded and analyzed. The saline volume required to achieve extravasation ranged from 0.2 to 60.0 mL. The median saline volume required to achieve extravasation was 9.7 mL (interquartile range, 3.8-29.6 mL); however, 5 of 42 patients required volumes between 50.0 and 60.0 mL. A total of 50.0 mL was required to achieve 90% sensitivity, 55.0 mL to achieve 95% sensitivity, and 60.0 mL to achieve 99% sensitivity. The previously recommended 30 mL of saline required to reliably detect traumatic arthrotomy of the ankle may be too small a volume. The present study suggests that clinicians should attempt to inject 60 mL of saline to effectively rule out a traumatic arthrotomy injury. Because of the study's methods involving an anteromedial arthrotomy with anterolateral saline injection, these findings may be most valid for arthrotomies on the medial side of the ankle.

The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation.

PubMed

Hesketh, Anthony J; Maloney, Caroline; Behr, Christopher A; Edelman, Morris C; Glick, Richard D; Al-Abed, Yousef; Symons, Marc; Soffer, Samuel Z; Steinberg, Bettie M

2015-01-01

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma.

Tumour-derived Interleukin 35 promotes pancreatic ductal adenocarcinoma cell extravasation and metastasis by inducing ICAM1 expression

PubMed Central

Huang, Chongbiao; Li, Na; Li, Zengxun; Chang, Antao; Chen, Yanan; Zhao, Tiansuo; Li, Yang; Wang, Xiuchao; Zhang, Wei; Wang, Zhimin; Luo, Lin; Shi, Jingjing; Yang, Shengyu; Ren, He; Hao, Jihui

2017-01-01

Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation. Mechanistically, IL-35 promotes ICAM1 overexpression through a GP130-STAT1 signalling pathway, which facilitates endothelial adhesion and transendothelial migration via an ICAM1–fibrinogen–ICAM1 bridge. In an orthotopic xenograft model, IL-35 promotes spontaneous pancreatic cancer metastasis in an ICAM1-dependent manner. Together, our results indicate additional functions of IL-35 in promoting PDAC metastasis through mediating ICAM1 expression. PMID:28102193

Perivascular iron deposits are associated with protein nitration in cerebral experimental autoimmune encephalomyelitis.

PubMed

Sands, Scott A; Williams, Rachel; Marshall, Sylvester; LeVine, Steven M

2014-10-17

Nitration of proteins, which is thought to be mediated by peroxynitrite, is a mechanism of tissue damage in multiple sclerosis (MS). However, protein nitration can also be catalyzed by iron, heme or heme-associated molecules independent of peroxynitrite. Since microhemorrhages and perivascular iron deposits are present in the CNS of MS patients, we sought to determine if iron is associated with protein nitration. A cerebral model of experimental autoimmune encephalomyelitis (cEAE) was utilized since this model has been shown to have perivascular iron deposits similar to those present in MS. Histochemical staining for iron was used together with immunohistochemistry for nitrotyrosine, eNOS, or iNOS on cerebral sections. Leakage of the blood-brain barrier (BBB) was studied by albumin immunohistochemistry. Iron deposits were colocalized with nitrotyrosine staining around vessels in cEAE mice while control animals revealed minimal staining. This finding supports the likelihood that nitrotyrosine formation was catalyzed by iron or iron containing molecules. Examples of iron deposits were also observed in association with eNOS and iNOS, which could be one source of substrates for this reaction. Extravasation of albumin was present in cEAE mice, but not in control animals. Extravasated albumin may act to limit tissue injury by binding iron and/or heme as well as being a target of nitration, but the protection is incomplete. In summary, iron-catalyzed nitration of proteins is a likely mechanism of tissue damage in MS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Peroxide as a Novel Treatment for Ecchymoses

PubMed Central

Sroa, Novie; Campbell, Shannon M.; Bechtel, Mark A.; Mitch Opremcak, E.

2010-01-01

Ecchymoses, commonly known as bruises, frequently occur after injury to the skin causes extravasation of red blood cells into interstitial tissue. This extravasation can lead to an inflammatory cascade. The case report presented details one patient who displayed rapid improvement in the pain and appearance of a partially treated bruise on her thigh after an eight-hour application of hydrogen peroxide 15% carbamide gel under occlusion. Hydrogen peroxide 15% carbamide gel may represent a novel treatment for ecchymoses. This potential new treatment for bruises needs to be studied further to detail its adverse effects, safety profile, and efficacy profile. PMID:21103315

Infiltration and extravasation: update on prevention and management.

PubMed

Doellman, Darcy; Hadaway, Lynn; Bowe-Geddes, Leigh Ann; Franklin, Michelle; LeDonne, Jack; Papke-O'Donnell, Lorelei; Pettit, Janet; Schulmeister, Lisa; Stranz, Marc

2009-01-01

Infiltration and extravasation are risks of intravenous administration therapy involving unintended leakage of solution into the surrounding tissue. Consequences range from local irritation to amputation. While immediate action using appropriate measures (ie, dilution, extraction, antidotes, and supportive treatments) can decrease the need for surgical intervention, many injuries may be prevented by following established policy and procedures. However, timely surgical intervention, when necessary, can prevent more serious adverse outcomes. Clinicians should be prepared to act promptly when an event occurs. Thorough incident documentation helps determine whether infusion care meets the standard of practice and is a keystone to medicolegal defense.

Glucocorticoid-induced tumor necrosis factor receptor family-related ligand triggering upregulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and promotes leukocyte adhesion.

PubMed

Lacal, Pedro Miguel; Petrillo, Maria Grazia; Ruffini, Federica; Muzi, Alessia; Bianchini, Rodolfo; Ronchetti, Simona; Migliorati, Graziella; Riccardi, Carlo; Graziani, Grazia; Nocentini, Giuseppe

2013-10-01

The interaction of glucocorticoid-induced tumor necrosis factor receptor-family related (GITR) protein with its ligand (GITRL) modulates different functions, including immune/inflammatory response. These effects are consequent to intracellular signals activated by both GITR and GITRL. Previous results have suggested that lack of GITR expression in GITR(-/-) mice decreases the number of leukocytes within inflamed tissues. We performed experiments to analyze whether the GITRL/GITR system modulates leukocyte adhesion and extravasation. For that purpose, we first evaluated the capability of murine splenocytes to adhere to endothelial cells (EC). Our results indicated that adhesion of GITR(-/-) splenocytes to EC was reduced as compared with wild-type cells, suggesting that GITR plays a role in adhesion and that this effect may be due to GITRL-GITR interaction. Moreover, adhesion was increased when EC were pretreated with an agonist GITR-Fc fusion protein, thus indicating that triggering of GITRL plays a role in adhesion by EC regulation. In a human in vitro model, the adhesion to human EC of HL-60 cells differentiated toward the monocytic lineage was increased by EC pretreatment with agonist GITR-Fc. Conversely, antagonistic anti-GITR and anti-GITRL Ab decreased adhesion, thus further indicating that GITRL triggering increases the EC capability to support leukocyte adhesion. EC treatment with GITR-Fc favored extravasation, as demonstrated by a transmigration assay. Notably, GITRL triggering increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and anti-ICAM-1 and anti-VCAM-1 Abs reversed GITR-Fc effects. Our study demonstrates that GITRL triggering in EC increases leukocyte adhesion and transmigration, suggesting new anti-inflammatory therapeutic approaches based on inhibition of GITRL-GITR interaction.

A simple diagnostic test to confirm correct intravascular placement of peripheral catheters in order to avoid extravasation.

PubMed

Keidan, Ilan; Sidi, Avner; Ben-Menachem, Erez; Derazne, Estela; Berkenstadt, Haim

2015-11-01

Intravenous catheters are ubiquitous among modern medical management of patients, yet misplaced or tissued cannulas can result in serious iatrogenic injury due to infiltration or extravasation of injectate. Prevention is difficult, and currently few reliable tests exist to confirm intravascular placement of catheters in awake spontaneously breathing patients. Twenty conscious spontaneously breathing healthy volunteers were injected with 50 mL normal saline and 50 mL 4.2%, or 50 mL 2.1%, or 20 mL 4.2% sodium bicarbonate in a random order. A blinded anesthetist observed continuous sampling of exhaled carbon dioxide and was asked to differentiate between the sodium bicarbonate and saline injections. Peak increase in measured exhaled carbon dioxide was also calculated. Exhaled carbon dioxide increased significantly in participants injected with intravenous sodium bicarbonate. Mean peak increase was 7.4 mm Hg (±2.1 mm Hg) for 50 mL 4.2% sodium bicarbonate, 4.7 mm Hg (±2.5 mm Hg) for 20 mL 4.2% sodium bicarbonate, and 3.5 mm Hg (±1. 8 mm Hg) for 50 mL 2.1% sodium bicarbonate. The blinded observer correctly identified the injection as sodium bicarbonate or normal saline in every instance. Intravenous injection of dilute sodium bicarbonate with exhaled carbon dioxide monitoring reliably confirms correct intravascular placement of a catheter. A transient increase of exhaled carbon dioxide by 10% or more is an objective and reliable confirmation of intravascular location of the catheter. We recommend using 20 mL of 4.2% sodium bicarbonate to minimize the mEq dose of sodium bicarbonate required. Copyright © 2015 Elsevier Inc. All rights reserved.

Divergent effects of norepinephrine, dopamine and substance P on the activation, differentiation and effector functions of human cytotoxic T lymphocytes

PubMed Central

2009-01-01

Background Neurotransmitters are important regulators of the immune system, with very distinct and varying effects on different leukocyte subsets. So far little is known about the impact of signals mediated by neurotransmitters on the function of CD8+ T lymphocytes. Therefore, we investigated the influence of norepinephrine, dopamine and substance P on the key tasks of CD8+ T lymphocytes: activation, migration, extravasation and cytotoxicity. Results The activation of naïve CD8+ T lymphocytes by CD3/CD28 cross-linking was inhibited by norepinephrine and dopamine, which was caused by a downregulation of interleukin (IL)-2 expression via Erk1/2 and NF-κB inhibition. Furthermore, all of the investigated neurotransmitters increased the spontaneous migratory activity of naïve CD8+ T lymphocytes with dopamine being the strongest inducer. In contrast, activated CD8+ T lymphocytes showed a reduced migratory activity in the presence of norepinephrine and substance P. With regard to extravasation we found norepinephrine to induce adhesion of activated CD8+ T cells: norepinephrine increased the interleukin-8 release from endothelium, which in turn had effect on the activated CXCR1+ CD8+ T cells. At last, release of cytotoxic granules from activated cells in response to CD3 cross-linking was not influenced by any of the investigated neurotransmitters, as we have analyzed by measuring the β-hexosamidase release. Conclusion Neurotransmitters are specific modulators of CD8+ T lymphocytes not by inducing any new functions, but by fine-tuning their key tasks. The effect can be either stimulatory or suppressive depending on the activation status of the cells. PMID:19968887

The in vivo pharmacological profile of a 5-HT1 receptor agonist, CP-122,288, a selective inhibitor of neurogenic inflammation.

PubMed

Gupta, P; Brown, D; Butler, P; Ellis, P; Grayson, K L; Land, G C; Macor, J E; Robson, S F; Wythes, M J; Shepperson, N B

1995-11-01

1. The aim of the present study was to investigate the in vivo pharmacological profile of CP-122,288, an indole-derivative with a conformationally restricted N-methylpyrrolidinyl basic side chain in the C-3 position. This C-3 substituent structurally differentiates CP-122,288 from the 5-HT1D receptor agonist sumatriptan, which possesses an N,N-dimethylaminoethyl group. [Formula: see text] 2. When administered prior to electrical stimulation of the trigeminal ganglion, CP-122,288 (0.3-300 ng kg-1, i.v.) produced a dose-related inhibition of plasma protein extravasation in rat dura mater (minimum effective dose, MED, 3 ng kg-1 i.v., P < 0.05; maximal inhibition of plasma extravasation at 30 ng kg-1 i.v., P < 0.01). Sumatriptan produced a similar inhibition of plasma leakage in the dura, but at much higher dose levels (MED, 100 micrograms kg-1 i.v., P < 0.05). Thus, CP-122,288 is of the order of 10(4) fold more potent than sumatriptan. 3. At all doses tested, CP-122,288 did not inhibit plasma protein extravasation measured in extracranial tissues such as the lower lip, eyelid, and conjunctiva. 4. In a separate series of studies in the anaesthetized rat, CP-122,288 (0.003-3 micrograms kg-1 i.v.) produced no change in either heart rate or mean arterial blood pressure, thus demonstrating that doses of CP-122,288 which inhibit plasma protein leakage in rat dura, are devoid of hemodynamic effects. 5. Following a 5 min period of electrical stimulation of the trigeminal ganglion, a 20 min period of sustained neurogenically-driven plasma extravasation, occurring in the absence of electrical stimulation, was initiated. By administration of the compound 5 min after completing the phase of electrical stimulation, this protocol permitted the evaluation of the activity of CP-122,288 on an ongoing and established inflammatory event. CP-122,288 (30 and 300 ng kg-1, i.v., P < 0.01 and P < 0.05, respectively) produced a complete inhibition of plasma protein leakage which was consistent with its effects when administered prior to trigeminal ganglion stimulation. 6. In the anaesthetized dog, CP-122,288 and sumatriptan, at 1-300 micrograms kg-1, i.v., produced a dose-dependent reduction in carotid arterial blood flow and coronary arterial diameter. These data demonstrate that sumatriptan inhibits neurogenic inflammation in the rat (MED, 100 micrograms kg-1, i.v.), and produces vasoconstriction in the dog, over a similar dose-range. Interestingly, doses of CP-122,288 that inhibit neurogenic inflammation in rat dura mater (0.3-300 ng kg-1) were demonstrated to be devoid of vasoconstrictor activity in either the carotid or coronary vascular beds of dog. 7. These data demonstrate that in the rat, CP-122,288 is a highly potent and selective inhibitor of neurogenic inflammation in intracranial tissues, at doses which are devoid of vasoconstrictor activity in dog. Potentially, CP-122,288 may be of use for the acute treatment of migraine, without the risk of cardiovascular side-effects.

A novel CGRP-neutralizing Spiegelmer attenuates neurogenic plasma protein extravasation

PubMed Central

Hoehlig, K; Johnson, K W; Pryazhnikov, E; Maasch, C; Clemens-Smith, A; Purschke, W G; Vauléon, S; Buchner, K; Jarosch, F; Khiroug, L; Vater, A; Klussmann, S

2015-01-01

Background and Purpose Calcitonin gene-related peptide (CGRP) plays an important role in the pathology of migraine, and recent clinical trials suggest the inhibition of CGRP-mediated processes as a new therapeutic option in migraine. In this study, we describe the generation of NOX-L41, a CGRP-neutralizing mirror-image (l-)aptamer (Spiegelmer) and investigate its in vitro and in vivo function. Experimental Approach A CGRP-binding Spiegelmer was identified by in vitro selection. Binding studies were performed using surface plasmon resonance (SPR), and the inhibitory activity was determined in cell-based assays. The pharmacokinetic profile comparing i.v. and s.c. dosing was analysed in rats. Intravital two-photon microscopy was employed to follow extravasation from meningeal vessels. Finally, in vivo efficacy was tested in a model of electrically evoked meningeal plasma protein extravasation (PPE) in rats. Key Results We identified NOX-L41, a novel CGRP-neutralizing Spiegelmer. SPR studies showed that NOX-L41 binds to human and rat/mouse CGRP with sub-nanomolar affinities and is highly selective against related peptides such as amylin. In vitro, NOX-L41 effectively inhibited CGRP-induced cAMP formation in SK-N-MC cells. In rats, NOX-L41 had a plasma half-life of 8 h. Pharmacodynamic studies showed that NOX-L41 extravasates from blood vessels in the dura mater and inhibits neurogenic meningeal PPE for at least 18 h after single dosing. Conclusions and Implications This is the first description of the CGRP-neutralizing Spiegelmer NOX-L41. Preclinical studies confirmed a role for CGRP in neurogenic PPE and provided proof-of-concept for the potential use of this new drug candidate for the treatment or prevention of migraine. PMID:25659966

Activation of the nociceptin/orphanin FQ receptor reduces bronchoconstriction and microvascular leakage in a rabbit model of gastroesophageal reflux

PubMed Central

D'Agostino, Bruno; Marrocco, Giuseppina; De Nardo, Marilisa; Calò, Girolamo; Guerrini, Remo; Gallelli, Luca; Advenier, Charles; Rossi, Francesco

2005-01-01

Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide ligand for a specific G-protein coupled receptor, the N/OFQ peptide receptor (NOP). The N/OFQ-NOP receptor system has been reported to play an important role in pain, anxiety and appetite regulation. In airways, N/OFQ was found to inhibit the release of tachykinins and the bronchoconstriction and cough provoked by capsaicin. Here we evaluated the effects of NOP receptor activation in bronchoconstriction and airway microvascular leakage induced by intraesophageal (i.oe.) hydrochloric acid (HCl) instillation in rabbits. We also tested the effects of NOP receptor activation in SP-induced plasma extravasation and bronchoconstriction. In anesthetized New Zealand rabbits bronchopulmonary function (total lung resistance (RL) and dynamic compliance (Cdyn)) and airway microvascular leakage (extravasation of Evans blue dye) were evaluated. Infusion of i.oe. HCl (1 N) led to a significant increase in bronchoconstriction and plasma extravasation in the main bronchi and trachea of rabbits pretreated with propranolol, atropine and phosphoramidon. Bronchoconstriction and airway microvascular leakage were inhibited by N/OFQ (3–30 μg kg−1 i.v.) in a dose-dependent manner. The NOP receptor agonist [Arg14,Lys15]N/OFQ mimicked the inhibitory effect of N/OFQ, being 10-fold more potent, UFP-101, a peptide selective NOP receptor antagonist, blocked the inhibitory effects of both agonists. Under the same experimental conditions, N/OFQ and [Arg14,Lys15]N/OFQ did not counteract the bronchoconstriction and airway microvascular leakage induced by substance P. These results suggest that bronchoconstriction and airway plasma extravasation induced by i.oe. HCl instillation are inhibited by activation of prejunctional NOP receptors. PMID:15685213

Dual-energy micro-CT imaging for differentiation of iodine- and gold-based nanoparticles

NASA Astrophysics Data System (ADS)

Badea, C. T.; Johnston, S. M.; Qi, Y.; Ghaghada, K.; Johnson, G. A.

2011-03-01

Spectral CT imaging is expected to play a major role in the diagnostic arena as it provides material decomposition on an elemental basis. One fascinating possibility is the ability to discriminate multiple contrast agents targeting different biological sites. We investigate the feasibility of dual energy micro-CT for discrimination of iodine (I) and gold (Au) contrast agents when simultaneously present in the body. Simulations and experiments were performed to measure the CT enhancement for I and Au over a range of voltages from 40-to-150 kVp using a dual source micro-CT system. The selected voltages for dual energy micro-CT imaging of Au and I were 40 kVp and 80 kVp. On a massconcentration basis, the relative average enhancement of Au to I was 2.75 at 40 kVp and 1.58 at 80 kVp. We have demonstrated the method in a preclinical model of colon cancer to differentiate vascular architecture and extravasation. The concentration maps of Au and I allow quantitative measure of the bio-distribution of both agents. In conclusion, dual energy micro-CT can be used to discriminate probes containing I and Au with immediate impact in pre-clinical research.

Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration across Brain and Lung Microvascular Endothelium

PubMed Central

Fan, Jie; Fu, Bingmei M.

2015-01-01

Tumor cell extravasation through the endothelial barrier forming the microvessel wall is a crucial step during tumor metastasis. However, where, how and how fast tumor cells transmigrate through endothelial barriers remain unclear. Using an in vitro transwell model, we performed a transmigration assay of malignant breast tumor cells (MDA-MB-231) through brain and lung microvascular endothelial monolayers under control and pathological conditions. The locations and rates of tumor cell transmigration as well as the changes in the structural components (integrity) of endothelial monolayers were quantified by confocal microscopy. Endothelial monolayer permeability to albumin Palbumin was also quantified under the same conditions. We found that about 98% of transmigration occurred at the joints of endothelial cells instead of cell bodies; tumor cell adhesion and transmigration degraded endothelial surface glycocalyx and disrupted endothelial junction proteins, consequently increased Palbumin; more tumor cells adhered to and transmigrated through the endothelial monolayer with higher Palbumin; Palbumin and tumor transmigration were increased by vascular endothelial growth factor (VEGF), a representative of cytokines, and lipopolysaccharides (LPS), a typical systemic inflammatory factor, but reduced by adenosine 3′, 5′-cyclic monophosphate (cAMP). These results suggest that reinforcing endothelial structural integrity is an effective approach for inhibiting tumor extravasation. PMID:26603751

Primary hepatic artery embolization in pediatric blunt hepatic trauma.

PubMed

Ong, Caroline C P; Toh, Luke; Lo, Richard H G; Yap, Te-Lu; Narasimhan, Kannan

2012-12-01

Non-operative management of isolated blunt hepatic trauma is recommended except when hemodynamic instability requires immediate laparotomy. Hepatic artery angioembolization is increasingly used for hepatic injuries with ongoing bleeding as demonstrated by contrast extravasation on the CT scan. It is used primarily or after laparotomy to control ongoing hemorrhage. Hepatic angioembolization as part of multimodality management of hepatic trauma is reported mainly in adults, with few pediatric case reports. We describe our institution experience with primary pediatric hepatic angioembolization and review the literature with regard to indications and complications. Two cases (3 and 8 years old), with high-grade blunt hepatic injuries with contrast extravasation on the CT scan were successfully managed by emergency primary hepatic angioembolization with minimal morbidity and avoided laparotomy. To date, the only reports of pediatric hepatic angioembolization for trauma are 5 cases for acute bleeding and 15 delayed cases for pseudoaneurysm. The role of hepatic angioembolization in the presence of an arterial blush on CT in adults is accepted, but contested in a pediatric series, despite higher transfusion rate and mortality rate. We propose that hepatic angioembolization should be considered adjunct treatment, in lieu of, or in addition to emergency laparotomy for hemostasis in pediatric blunt hepatic injury. Copyright © 2012 Elsevier Inc. All rights reserved.

Drug-Loaded Nanoemulsions/Microbubbles for Combined Tumor Imaging and Therapy

NASA Astrophysics Data System (ADS)

Rapoport, Natalya; Gao, Zhonggao; Kennedy, Ann

2007-05-01

A new class of multifunctional nanoparticles that combine properties of polymeric drug carriers, ultrasound imaging contrast agents, and enhancers of ultrasound-mediated intracellular drug delivery was developed. At room temperature, the developed systems comprise perfluorocarbon nanodroplets stabilized by the walls made of biodegradable block copolymers. The nanodroplets convert into microbubbles upon heating to physiological temperatures. The phase state of the systems and nanodroplet size may be controlled by the copolymer/perfluorocarbon volume ratio. Three areas observed in phase diagrams correspond to micelles; micelle/microbubble coexistence; and nano/microbubble coexistence. These systems manifest a relatively high drug loading capacity (about 15 % wt/wt). As indicated by biodistribution measurements and ultrasound imaging, the micelles and nanobubbles extravasate selectively into the tumor interstitia. Microbubble cavitate and collapse under the action of tumor-directed ultrasound, resulting in a dramatically enhanced intracellular drug uptake by the tumor cells. Upon intravenous injections, a long-lasting, strong and selective ultrasound contrast is observed in the tumor volume confirming nanobubble extravasation through the defected tumor microvasculature and suggesting their coalescence into larger, highly echogenic microbubbles in the tumor tissue. This effect is tumor-selective; no accumulation of echogenic microbubbles is observed in other organs. Tumor contrast increases in time confirming gradual accumulation of echogenic microbubbles in the tumor tissue, presumably via the enhanced penetration and retention (EPR) effect.

Development of a Single-Cell Migration and Extravasation Platform through Selective Surface Modification.

PubMed

Roberts, Steven A; Waziri, Allen E; Agrawal, Nitin

2016-03-01

Cell migration through three-dimensional (3D) tissue spaces is integral to many biological and pathological processes, including metastasis. Circulating tumor cells (CTCs) are phenotypically heterogeneous, and in vitro analysis of their extravasation behavior is often impeded by the inability to establish complex tissue-like extracellular matrix (ECM) environments and chemotactic gradients within microfluidic devices. We have developed a novel microfluidic strategy to manipulate surface properties of enclosed microchannels and create 3D ECM structures for real-time observation of individual migrating cells. The wettability of selective interconnected channels is controlled by a plasma pulse, enabling the incorporation of ECM exclusively within the transmigration regions. We applied this approach to collectively analyze CTC-endothelial adhesion, trans-endothelial migration, and subsequent motility of breast cancer cells (MDA-MB-231) through a 3D ECM under artificial gradients of SDF-1α. We observed migration velocities ranging from 5.12 to 12.8 μm/h, which closely correspond to single-cell migration in collagen blocks, but are significantly faster than the migration of cell aggregates. The compartmentalized microchannels separated by the porous ECM makes this in vitro assay versatile and suitable for a variety of applications such as inflammation studies, drug screening, and coculture interactions.

Pulmonary sustained release of insulin from microparticles composed of polyelectrolyte layer-by-layer assembly.

PubMed

Amancha, Kiran Prakash; Balkundi, Shantanu; Lvov, Yuri; Hussain, Alamdar

2014-05-15

The present study tests the hypothesis that layer-by-layer (LbL) nanoassembly of thin polyelectrolyte films on insulin particles provides sustained release of the drug after pulmonary delivery. LbL insulin microparticles were formulated using cationic and anionic polyelectrolytes. The microparticles were characterized for particle size, particle morphology, zeta potential and in vitro release. The pharmacokinetics and pharmacodynamics of drug were assessed by measuring serum insulin and glucose levels after intrapulmonary administration in rats. Bronchoalveolar lavage (BAL) and evans blue (EB) extravasation studies were performed to investigate the cellular or biochemical changes in the lungs caused by formulation administration. The mass median aerodynamic diameter (MMAD) of the insulin microparticles was 2.7 μm. Confocal image of the formulation particles confirmed the polyelectrolyte deposition around the insulin particles. Zeta potential measurements showed that there was charge reversal after each layering. Pulmonary administered LbL insulin formulation resulted in sustained serum insulin levels and concomitant decrease in serum glucose levels. The BAL and EB extravasation studies showed that the LbL insulin formulation did not elicit significant increase in marker enzymes activities compared to control group. These results demonstrate that the sustained release of insulin could be achieved using LbL nanoassembly around the insulin particles. Copyright © 2014 Elsevier B.V. All rights reserved.

Genome-wide in vivo screen identifies novel host regulators of metastatic colonization.

PubMed

van der Weyden, Louise; Arends, Mark J; Campbell, Andrew D; Bald, Tobias; Wardle-Jones, Hannah; Griggs, Nicola; Velasco-Herrera, Martin Del Castillo; Tüting, Thomas; Sansom, Owen J; Karp, Natasha A; Clare, Simon; Gleeson, Diane; Ryder, Edward; Galli, Antonella; Tuck, Elizabeth; Cambridge, Emma L; Voet, Thierry; Macaulay, Iain C; Wong, Kim; Spiegel, Sarah; Speak, Anneliese O; Adams, David J

2017-01-12

Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment ('host', which includes stromal cells and the immune system). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth ('colonization') being critical in determining metastatic outcome. Here we show the results of screening 810 mutant mouse lines using an in vivo assay to identify microenvironmental regulators of metastatic colonization. We identify 23 genes that, when disrupted in mouse, modify the ability of tumour cells to establish metastatic foci, with 19 of these genes not previously demonstrated to play a role in host control of metastasis. The largest reduction in pulmonary metastasis was observed in sphingosine-1-phosphate (S1P) transporter spinster homologue 2 (Spns2)-deficient mice. We demonstrate a novel outcome of S1P-mediated regulation of lymphocyte trafficking, whereby deletion of Spns2, either globally or in a lymphatic endothelial-specific manner, creates a circulating lymphopenia and a higher percentage of effector T cells and natural killer (NK) cells present in the lung. This allows for potent tumour cell killing, and an overall decreased metastatic burden.

Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream.

PubMed

Weber, Martin R; Zuka, Masahiko; Lorger, Mihaela; Tschan, Mario; Torbett, Bruce E; Zijlstra, Andries; Quigley, James P; Staflin, Karin; Eliceiri, Brian P; Krueger, Joseph S; Marchese, Patrizia; Ruggeri, Zaverio M; Felding, Brunhilde H

2016-04-01

Metastasis is the main cause of death in cancer patients, and understanding mechanisms that control tumor cell dissemination may lead to improved therapy. Tumor cell adhesion receptors contribute to cancer spreading. We noted earlier that tumor cells can expressing the adhesion receptor integrin αvβ3 in distinct states of activation, and found that cells which metastasize from the blood stream express it in a constitutively high affinity form. Here, we analyzed steps of the metastatic cascade in vivo and asked, when and how the affinity state of integrin αvβ3 confers a critical advantage to cancer spreading. Following tumor cells by real time PCR, non-invasive bioluminescence imaging, intravital microscopy and histology allowed us to identify tumor cell extravasation from the blood stream as a rate-limiting step supported by high affinity αvβ3. Successful transendothelial migration depended on cooperation between tumor cells and platelets involving the high affinity tumor cell integrin and release of platelet granules. Thus, this study identifies the high affinity conformer of integrin αvβ3 and its interaction with platelets as critical for early steps during hematogenous metastasis and target for prevention of metastatic disease. © 2016 Elsevier Ltd. All rights reserved.

Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream

PubMed Central

Weber, Martin R.; Zuka, Masahiko; Lorger, Mihaela; Tschan, Mario; Torbett, Bruce E.; Zijlstra, Andries; Quigley, James P.; Staflin, Karin; Eliceiri, Brian P.; Krueger, Joseph S.; Marchese, Patricia; Ruggeri, Zaverio M.; Felding, Brunhilde H.

2016-01-01

Metastasis is the main cause of death in cancer patients, and understanding mechanisms that control tumor cell dissemination may lead to improved therapy. Tumor cell adhesion receptors contribute to cancer spreading. We noted earlier that tumor cells can expressing the adhesion receptor integrin αvβ3 in distinct states of activation, and found that cells which metastasize from the blood stream express it in a constitutively high affinity form. Here, we analyzed steps of the metastatic cascade in vivo and asked, when and how the affinity state of integrin αvβ3 confers a critical advantage to cancer spreading. Following tumor cells by real time PCR, non-invasive bioluminescence imaging, intravital microscopy and histology allowed us to identify tumor cell extravasation from the blood stream as a rate-limiting step supported by high affinity αvβ3. Successful transendothelial migration depended on cooperation between tumor cells and platelets involving the high affinity tumor cell integrin and release of platelet granules. Thus, this study identifies the high affinity conformer of integrin αvβ3 and its interaction with platelets as critical for early steps during hematogenous metastasis and target for prevention of metastatic disease. PMID:27067975

Integrins in T Cell Physiology

PubMed Central

Alabiso, Oscar; Galetto, Alessandra Silvia; Baldanzi, Gianluca

2018-01-01

From the thymus to the peripheral lymph nodes, integrin-mediated interactions with neighbor cells and the extracellular matrix tune T cell behavior by organizing cytoskeletal remodeling and modulating receptor signaling. LFA-1 (αLβ2 integrin) and VLA-4 (α4β1 integrin) play a key role throughout the T cell lifecycle from thymocyte differentiation to lymphocyte extravasation and finally play a fundamental role in organizing immune synapse, providing an essential costimulatory signal for the T cell receptor. Apart from tuning T cell signaling, integrins also contribute to homing to specific target organs as exemplified by the importance of α4β7 in maintaining the gut immune system. However, apart from those well-characterized examples, the physiological significance of the other integrin dimers expressed by T cells is far less understood. Thus, integrin-mediated cell-to-cell and cell-to-matrix interactions during the T cell lifespan still represent an open field of research. PMID:29415483

Premature extravasation. A bleeding site identified during the dynamic phase of Tc-99m red blood cell bleeding scintigraphy.

PubMed

el-Shirbiny, A; Fernandez, R; Zuckier, L S

1995-08-01

Tc-99m RBC scintigraphy is favored by many investigators because it provides the ability to image the abdomen over a prolonged period of time, thereby allowing identification of delayed bleeding sites that are frequently encountered due to the intermittent nature of gastrointestinal bleeding. The authors describe a case of bleeding scintigraphy with labeled red blood cells in which the bleeding site was identifiable only on the dynamic blood-flow and first static images. On later images, the labeled blood cells had spread throughout the colon, rendering localization of the actual bleeding site impossible. Two previous red blood cell scintigraphies and a subsequent contrast angiogram did not reveal sites of active bleeding. As illustrated by this unusual case, factors governing timing and visualization of abnormal bleeding sites are discussed, as is a differential diagnosis of abnormal foci of activity seen on the dynamic phase of bleeding scintigraphy.

Fluorescence Imaging/Agents in Tumor Resection.

PubMed

Stummer, Walter; Suero Molina, Eric

2017-10-01

Intraoperative fluorescence imaging allows real-time identification of diseased tissue during surgery without being influenced by brain shift and surgery interruption. 5-Aminolevulinic acid, useful for malignant gliomas and other tumors, is the most broadly explored compound approved for fluorescence-guided resection. Intravenous fluorescein sodium has recently received attention, highlighting tumor tissue based on extravasation at the blood-brain barrier (defective in many brain tumors). Fluorescein in perfused brain, unselective extravasation in brain perturbed by surgery, and propagation with edema are concerns. Fluorescein is not approved but targeted fluorochromes with affinity to brain tumor cells, in development, may offer future advantages. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Upgrading of the micro-marsupialisation technique for the management of mucus extravasation or retention phenomena.

PubMed

Amaral, M B F; de Freitas, J B; Mesquita, R A

2012-12-01

This study evaluated the performance of an upgrading of the micro-marsupialisation technique for the management of mucus extravasation or retention phenomena. This study presents a prospective case series of management of ranulas and mucoceles, with a follow-up ranging from 6 to 18 months. Data included the age and gender of patients, as well as the type, size, and site of lesions, and number of punctures. The treatment performance was evaluated according to: postoperative pain, oedema, secondary infection, clinical healing, retreatment, and recurrence of the lesions. All patients showed clinical healing of the lesions within 30 days after the micro-marsupialisation technique. None of patients presented a recurrence or required retreatment, there was no oedema or infection. No pain, or mild pain was reported by the majority of patients (58.81%). Micro-marsupialisation proved to be a simple, low cost, relatively non-invasive, painless, effective, and low recurrence technique to treat mucus extravasation or retention phenomena. Micro-marsupialisation can be recommended primarily to treat oral ranulas and selected mucoceles. Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation

PubMed Central

Hesketh, Anthony J.; Maloney, Caroline; Behr, Christopher A.; Edelman, Morris C.; Glick, Richard D.; Al-Abed, Yousef; Symons, Marc; Soffer, Samuel Z.; Steinberg, Bettie M.

2015-01-01

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma. PMID:26709919

Temporal and Spatial Effects of Blast Overpressure on Blood-Brain Barrier Permeability in Traumatic Brain Injury.

PubMed

Kuriakose, Matthew; Rama Rao, Kakulavarapu V; Younger, Daniel; Chandra, Namas

2018-06-06

Blast-induced traumatic brain injury (bTBI) is a "signature wound" in soldiers during training and in combat and has also become a major cause of morbidity in civilians due to increased insurgency. This work examines the role of blood-brain barrier (BBB) disruption as a result of both primary biomechanical and secondary biochemical injury mechanisms in bTBI. Extravasation of sodium fluorescein (NaF) and Evans blue (EB) tracers were used to demonstrate that compromise of the BBB occurs immediately following shock loading, increases in intensity up to 4 hours and returns back to normal in 24 hours. This BBB compromise occurs in multiple regions of the brain in the anterior-posterior direction of the shock wave, with maximum extravasation seen in the frontal cortex. Compromise of the BBB is confirmed by (a) extravasation of tracers into the brain, (b) quantification of tight-junction proteins (TJPs) in the brain and the blood, and (c) tracking specific blood-borne molecules into the brain and brain-specific proteins into the blood. Taken together, this work demonstrates that the BBB compromise occurs as a part of initial biomechanical loading and is a function of increasing blast overpressures.

Capillary permeability induced by intravenous neurokinins. Receptor characterization and mechanism of action.

PubMed

Jacques, L; Couture, R; Drapeau, G; Regoli, D

1989-08-01

The effects on plasma extravasation of three increasing doses from 6.5 pmol to 650 nmol/kg of substance P (SP), SP fragments, neurokinin A (NKA), neurokinin B (NKB) and selective agonists for neurokinin receptors were assessed in three cutaneous tissues (skin of hind paws, dorsal skin and ears) by intravenous (i.v.) administration in the pentobarbitone anaesthetized rat. Dose-dependent increases in plasma extravasation were observed with the following rank orders of potency (SP greater than NKA greater than NKB) for neurokinins and (SP greater than [p-Glu6]SP(6-11) greater than SP(4-11) greater than [p-Glu5]SP(5-11) greater than SP(7-11] for C-terminal SP fragments. The metabolically stable SP analogue [p-Glu5, MePhe8, Sar9]SP(5-11) was slightly more potent than [p-Glu5]SP(5-11). The N-terminal fragments SP(1-4), SP(1-7) and SP(1-9) were inactive up to 650 nmol/kg. The NK-1 receptor selective agonists [Sar9, Met(O2)11]SP and [beta-Ala4, Sar9, Met (O2)11]SP(4-11) were more potent than the NK-2 [( Nle10]NKA(4-10] and NK-3 [( MePhe7]NKB and [beta-Asp4, MePhe7]NKB(4-10] receptor selective agonists. Plasma extravasation induced by SP (6.5 nmol/kg) was unchanged in the presence of atropine, methysergide, diphenhydramine or during the i.v. and intra-arterial (i.a.) infusion of D-Arg0[Hyp3.D-Phe7]BK, an antagonist of bradykinin. Plasma extravasation induced by SP and [Sar9, Met(O2)11]SP was significantly reduced by indomethacin while that induced by NKA, NKB, [beta-Ala4, Sar9, Met(O2)11]SP(4-11), SP(4-11) and [p-Glu6]SP(6-11) was unaffected by the cyclooxygenase inhibitor. Compound 48/80 (0.75 mg/kg), histamine (10 mg/kg) and 5-HT (10 mg/kg) caused an increase in plasma extravasation, only the effect of compound 48/80 was abolished by indomethacin. Pretreatment with compound 48/80 prevented its own action on plasma extravasation and significantly reduced that induced by 6.5 nmol/kg of SP. These results rule out the involvement of acetylcholine (muscarinic receptors), 5-HT (5-HT1 and 5-HT2 receptors), histamine (H1 receptors) and kinins (B2 receptors) in the response to SP and indicate that the two positively charged amino acids (Arg, Lys) at the N-terminal end of the SP molecule are essential to trigger the release of prostaglandins from mast cells. This mechanism is responsible for the indirect effect of SP and related peptides on capillary permeability and does not appear to be mediated by a selective SP receptor. In addition, neurokinins may increase capillary permeability by direct activation of a NK-1 receptor type on the vascular endothelium.

Tourniquet application and epinephrine injection to penile skin: is it safe?

PubMed

Cakmak, M; Caglayan, F; Kisa, U; Bozdogan, O; Saray, A; Caglayan, O

2002-09-01

Although a tourniquet is frequently used in penile surgery there is still no consensus on safe application time. The aim of the present study is to investigate the effect of malondialdehyde (MDA) levels and histological changes in skin flaps after penile tourniquet application and epinephrine injection. A total of 36 male white New Zealand rabbits were randomly divided into six groups each containing six animals. A Mathieu-like flap was raised in all of the groups and a tourniquet was applied and the penis was subjected to ischemia for 10, 20 and 40 min in groups 1, 2 and 3, respectively. The flaps were then allowed to reperfuse for 5 min. Biopsies for MDA measurement were harvested in these groups. Subcutaneous 1/200,000 epinephrine was injected into penile skin in group 4 and 5 rabbits and biopsies for MDA measurement were harvested 10 and 40 min after injection. The control group was anesthetized without tourniquet usage or epinephrine injection. Specimens taken from the harvested flaps of all groups were submitted for histological evaluation. The mean MDA levels in all experimental groups were higher than in the control group and the difference was statistically significant. Edema, congestion and extravasation were observed in groups 1, 2 and 3. Minimal congestion and edema were observed in group 4 and severe edema and extravasation in group 5. Tourniquet usage for a duration of less than 10 min is clearly safer than prolonged usage. Epinephrine injection to penile skin may show a deleterious effect on wound healing.

Corrosion casting of the subglottis following endotracheal tube intubation injury: a pilot study in Yorkshire piglets

PubMed Central

2013-01-01

Purpose Subglottic stenosis can result from endotracheal tube injury. The mechanism by which this occurs, however, is not well understood. The purpose of this study was to examine the role of angiogenesis, hypoxia and ischemia in subglottic mucosal injury following endotracheal intubation. Methods Six Yorkshire piglets were randomized to either a control group (N=3, ventilated through laryngeal mask airway for corrosion casting) or accelerated subglottic injury group through intubation and induced hypoxia as per a previously described model (N=3). The vasculature of all animals was injected with liquid methyl methacrylate. After polymerization, the surrounding tissue was corroded with potassium hydroxide. The subglottic region was evaluated using scanning electron microscopy looking for angiogenic and hypoxic or degenerative features and groups were compared using Mann–Whitney tests and Friedman’s 2-way ANOVA. Results Animals in the accelerated subglottic injury group had less overall angiogenic features (P=.002) and more overall hypoxic/degenerative features (P=.000) compared with controls. Amongst angiogenic features, there was decreased budding (P=.000) and a trend toward decreased sprouting (P=.037) in the accelerated subglottic injury group with an increase in intussusception (P=.004), possibly representing early attempts at rapid revascularization. Amongst hypoxic/degenerative features, extravasation was the only feature that was significantly higher in the accelerated subglottic injury group (P=.000). Conclusions Subglottic injury due to intubation and hypoxia may lead to decreased angiogenesis and increased blood vessel damage resulting in extravasation of fluid and a decreased propensity toward wound healing in this animal model. PMID:24401165

An umbilical venous catheter complication presented as acute abdomen: case report.

PubMed

Oztan, Mustafa O; Ilhan, Ozkan; Abay, Elif; Koyluoglu, Gokhan

2016-12-01

Umbilical venous catheterization has become a widely accepted intravenous route for premature babies. These catheters allow administration of parenteral nutrition and medication and facilitate blood sampling. Besides these benefits, they also have significant potential complications like portal vein thrombosis, infection, vascular or hepatic injury, arrhythmia and sepsis. One of the rare but important complication is extravasation of the fluids due to misplacement of the catheter. The typical symptoms of this condition are sudden deterioration, hepatic enlargement, hematocrit drop, hypotension and abdominal distension. We herein present a premature newborn with unusual acute abdomen findings suggesting a surgical pathology after the extravasation of total parenteral nutrition into the abdomen. Sociedad Argentina de Pediatría.

Quality improvement project to reduce infiltration and extravasation events in a pediatric hospital.

PubMed

Tofani, Barbara F; Rineair, Sylvia A; Gosdin, Craig H; Pilcher, Patricia M; McGee, Susan; Varadarajan, Kartik R; Schoettker, Pamela J

2012-12-01

A safety event response team at Cincinnati Children's Hospital Medical Center developed and tested improvement strategies to reduce peripheral intravenous (PIV) infiltration and extravasation injuries. Improvement activities included development of the touch-look-compare method for hourly PIV site assessment, staff education and mandatory demonstration of PIV site assessment, and performance monitoring and sharing of compliance results. We observed a significant reduction in the injury rate immediately following implementation of the interventions that corresponded with monitoring compliance in performing hourly assessments on patients with a PIV, but this was not sustained. The team is currently examining other strategies to reduce PIV injuries. Copyright © 2012 Elsevier Inc. All rights reserved.

A 90-Kilodalton Endothelial Cell Molecule Mediating Lymphocyte Binding in Humans

NASA Astrophysics Data System (ADS)

Salmi, Marko; Jalkanen, Sirpa

1992-09-01

Interactions between leukocyte surface receptors and their ligands on vascular endothelial cells control lymphocyte traffic between the blood and various lymphoid organs, as well as extravasation of leukocytes into sites of inflammation. A heretofore undescribed 90-kilodalton human endothelial cell adhesion molecule (VAP-1) defined by a monoclonal antibody 1B2 is described. The expression pattern, molecular mass, functional properties, and an amino-terminal amino acid sequence define VAP-1 as an endothelial ligand for lymphocytes. VAP-1 helps to elucidate the complex heterotypic cell interactions that direct tissue-selective lymphocyte migration in man.

A new concept of the pathogenesis of oral mucous cysts based on a study of 200 cases.

PubMed

Praetorius, F; Hammarstrom, L

1992-05-01

A new hypothesis regarding the pathogenesis of mucous cysts of the oral mucosa is proposed. Based upon a histological study of 188 mucous cysts without epithelial lining out of a total of 200 cysts it is claimed that some cysts may not develop in any of the hitherto described ways as intraductal "mucous retention cysts" or extraductal "mucous extravasation cysts" or from destruction of acini due to the pressure of mucous caused by duct obstruction. It is suggested that some of the cysts, that are found to have developed intraglandularly, are caused by traumatic destruction of a large amount of glandular acini ("parenchymal destruction cysts") and continuous secretion from the remaining acini. The mucus from the disintegrated cells forms a pool, which in time is surrounded by a connective tissue capsule that contains remnants of parenchyma from the affected lobule. This parenchyma degenerates, and eventually the cyst shows the same histological picture as the "mucous extravasation cyst". It is argued that the presence of a feeder duct does not necessarily indicate an extravasation cyst, but may be seen in the "parenchymal destruction cysts" as well. Of the 188 cysts examined 20 (11 per cent) were found to develop intraglandularly, and 36 (19 per cent) were considered probably to have developed intraglandularly.

Targeted disruption of deep-lying neocortical microvessels in rat using ultrashort laser pulses

NASA Astrophysics Data System (ADS)

Nishimura, Nozomi; Schaffer, Christopher B.; Friedman, Beth; Tsai, Philbert S.; Lyden, Patrick D.; Kleinfeld, David

2004-06-01

The study of neurovascular diseases such as vascular dementia and stroke require novel models of targeted vascular disruption in the brain. We describe a model of microvascular disruption in rat neocortex that uses ultrashort laser pulses to induce localized injury to specific targeted microvessels and uses two-photon microscopy to monitor and guide the photodisruption process. In our method, a train of high-intensity, 100-fs laser pulses is tightly focused into the lumen of a blood vessel within the upper 500 μm of cortex. Photodisruption induced by these laser pulses creates injury to a single vessel located at the focus of the laser, leaving the surrounding tissue intact. This photodisruption results in three modalities of localized vascular injury. At low power, blood plasma extravasation can be induced. The vessel itself remains intact, while serum is extravasated into the intercellular space. Localized ischemia caused by an intravascular clot results when the photodisruption leads to a brief disturbance of the vascular walls that initiates an endogenous clotting cascade. The formation of a localized thrombus stops the blood flow at the location of the photodisruption. A hemorrhage, defined as a large extravasation of blood including plasma and red blood cells, results when higher laser power is used. The targeted vessel does not remain intact.

[Oncological emergencies in chemotherapy : Febrile neutropenia, tumor lysis syndrome, and extravasation].

PubMed

von Amsberg, G

2018-05-01

Uro-oncological emergencies can be caused by the tumor, treatment complications, or non-oncological diseases. This review focuses on chemotherapy-associated emergencies, especially febrile neutropenia (FN), tumor lysis syndrome (TLS), and extravasations. The goal is to provide an overview on the most relevant chemotherapy-associated emergencies and treatment methods. The ESMO (European Society of Medical Oncology), EORTC (European Organization for Research and Treatment of Cancer), and S3 guidelines were used for the preparation of this review and a PubMed search was performed for "febrile neutropenia", "extravasation", and "tumor lysis syndrome". A selection of the most relevant articles was included. A comprehensive medical history and examination are prerequisite for optimal treatment of chemotherapy-associated emergencies. The following aspects are of special interest: the malignant disease (tumor proliferation rate and burden); the applied medication (e. g., risk of FN, tissue damaging potential); the physical condition of the patient; age and relevant concomitant diseases (e. g., cardiovascular disease). Based on the diagnosis and the individual risk profile, therapeutic procedures are initiated. Distinct complications require an interdisciplinary treatment strategy. New treatment options such as checkpoint inhibitors complicate diagnosis and treatment of uro-oncological emergencies. Thus, improved diagnostic tools are required to draw the right conclusions in an emergency.

Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation.

PubMed

Zhao, Yunge; Sharma, Ashish K; LaPar, Damien J; Kron, Irving L; Ailawadi, Gorav; Liu, Yuan; Jones, David R; Laubach, Victor E; Lau, Christine L

2011-05-01

Ischemia-reperfusion (IR) injury following lung transplantation remains a major source of early morbidity and mortality. Histologically, this inflammatory process is characterized by neutrophil infiltration and activation. We previously reported that lung IR injury was significantly attenuated in plasminogen activator inhibitor-1-deficient mice. In this study, we explored the potential role of tissue plasminogen activator (tPA) in a mouse lung IR injury model. As a result, tPA knockout (KO) mice were significantly protected from lung IR injury through several mechanisms. At the cellular level, tPA KO specifically blocked neutrophil extravasation into the interstitium, and abundant homotypic neutrophil aggregation (HNA) was detected in the lung microvasculature of tPA KO mice after IR. At the molecular level, inhibition of neutrophil extravasation was associated with reduced expression of platelet endothelial cell adhesion molecule-1 mediated through the tPA/ LDL receptor-related protein/NF-κB signaling pathway, whereas increased P-selectin triggered HNA. At the functional level, tPA KO mice incurred significantly decreased vascular permeability and improved lung function following IR. Protection from lung IR injury in tPA KO mice occurs through a fibrinolysis-independent mechanism. These results suggest that tPA could serve as an important therapeutic target for the prevention and treatment of acute IR injury after lung transplantation.

Looking for the Ideal Particle: An Experimental Embolization Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Senturk, Cagin, E-mail: caginsenturk@yahoo.co; Cakir, Volkan; Yorukoglu, Kutsal

This study sought to compare the most frequently used embolic particles in an animal model. In 16 New Zealand white rabbits, right renal arteries were embolized using four different embolic particles (polyvinyl alcohol [PVA] particles, 150-250 {mu}m; PVA microspheres [PVAMs], 150-300 {mu}m; Tris-acryl gelatin microspheres [TGMs], 100-300 {mu}m; expanding microspheres [EXMs], 50-100 {mu}m). Quantity of embolic material used, embolization time, and angiographic patterns were documented. Fourteen days later, a control angiography was done to document angiographic recanalization and all animals were sacrificed. Histopathological specimens were analyzed for microscopic appearance and granulometric size of the particles, extravasation of the particles, perivascularmore » inflammation, and neocapillarization. The volume of the infarct area in each kidney was calculated. Results revealed a significantly lesser amount of embolic material used in the EXM group (p = 0.020). The angiographic recanalization rate in the EXM group (100%), compared with the PVA (0%) and TGM (0%) groups, was found to be statistically significant (p = 0.014). Although 75% of the renal arteries embolized with PVAMs were recanalized, this was not found to be statistically significant (p = 0.071). Occlusion levels in the PVA group were more proximal than with any of the microspheres. While there was no extravasation in the TGM group, extravasation rates in the PVA, PVAM, and EXM groups were 50%, 25%, and 75%, respectively. A mild degree of inflammation was noted in the PVA, PVAM, and TGM groups. EXMs caused a moderate degree of inflammation in two kidneys (50%). There was neocapillarization in the vessel lumen in all kidneys in the PVA and PVAM groups. The difference was significant (p = 0.014) compared with the TGM and EXM groups, which did not have any neocapillarization. Regarding infarct area volumes, the difference among the groups was significant (p = 0.022). EXMs caused significantly (p = 0.021) less infarction than the other embolic agents. We conclude that EXMs are less efficient due to a high recanalization rate and lesser volume of infarct compared with the other embolic agents in the rabbit kidney model. The most efficient embolization was seen in kidneys embolized with TGMs.« less

Atrial natriuretic factor increases splenic microvascular pressure and fluid extravasation in the rat.

PubMed

Sultanian, R; Deng, Y; Kaufman, S

2001-05-15

The spleen is an important site of atrial natriuretic factor (ANF)-induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood-perfused (1 ml min(-1)) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1-28), infused into the splenic artery of anaesthetized male rats, caused a dose-dependent (0.3-59 pmol min(-1)) increase in microvascular pressure from 11.3 +/- 0.7 to 14.9 +/- 0.5 mmHg and in post-capillary resistance from 7.2 +/- 0.6 to 10.1 +/- 1.1 mmHg ml(-1). ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min(-1)) caused a sustained increase in intrasplenic fluid efflux from 0.1 +/- 0.1 to 0.3 +/- 0.1 ml min(-1), and in capillary filtration coefficient (Kf) from 1.2 +/- 0.5 to 2.4 +/- 0.6 ml mmHg-1 min-1 (100 g tissue)-1. Mechanical elevation of splenic intravascular pressure (from 11.3 +/- 0.7 to 22.4 +/- 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 +/- 0.3 to 1.4 +/- 0.3 ml min(-1)). The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol min(-1)) did not alter splenic intravascular pressure or pre-/post-capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min-1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), inhibited the ANF-induced changes in splenic microvascular pressure and post-capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post-capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA.

Increased Potency of the PHSCN Dendrimer as an Inhibitor of Human Prostate Cancer Cell Invasion, Extravasation, and Lung Colony Formation

PubMed Central

Yao, Hongren; Zeng, Zhao-Zhu; Fay, Kevin S.; Staszewski, Evan D.; Veine, Donna M.; Livant, Donna L.

2011-01-01

Background Activated α5β1 integrin occurs specifically on tumor cells and on endothelial cells of tumor–associated vasculature, and plays a key role in invasion and metastasis. The PHSCN peptide (Ac-PHSCN-NH2) preferentially binds activated α5β1, to block invasion in vitro, and inhibit growth, metastasis and tumor recurrence in preclinical models of prostate cancer. In Phase I clinical trial, systemic Ac-PHSCN-NH2 monotherapy was well tolerated, and metastatic disease progression was prevented for 4–14 months in one third of treated patients. Results We have developed a significantly more potent derivative, the PHSCN-polylysine dendrimer (Ac-PHSCNGGK-MAP). Using in vitro invasion assays with naturally serum-free basement membranes, we observed that the PHSCN dendrimer was 130– to 1900–fold more potent than the PHSCN peptide at blocking α5β1–mediated invasion by DU 145 and PC-3 human prostate cancer cells, whether invasion was induced by serum, or by the Ac-PHSRN-NH2 peptide, under serum-free conditions. The PHSCN dendrimer was also approximately 800 times more effective than PHSCN peptide at preventing DU 145 and PC-3 extravasation in the lungs of athymic mice. Chou-Talalay analysis suggested that inhibition of both invasion in vitro and extravasation in vivo by the PHSCN dendrimer are highly synergistic. We found that many extravasated DU 145 and PC-3 cells go on to develop into metastatic colonies, and that a single pretreatment with the PHSCN dendrimer was 100–fold more affective than the PHSCN peptide at reducing lung colony formation. Conclusions Since many patients newly diagnosed with prostate cancer already have locally advanced or metastatic disease, the availability of a well-tolerated, nontoxic systemic therapy, like the PHSCN dendrimer, which prevents metastatic progression by inhibiting invasion, could be very beneficial. PMID:20339907

Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic Complications.

PubMed

Bonatti, M; Lombardo, F; Zamboni, G A; Vittadello, F; Currò Dossi, R; Bonetti, B; Pozzi Mucelli, R; Bonatti, G

2018-01-18

Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications. Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables. Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not ( P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not ( P < .001). Median maximum iodine concentration was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4 mg/mL in the patients who did not ( P < .001). Maximum iodine concentration showed an area under the curve of 0.89 for identifying patients developing intracerebral hemorrhage. The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with 100% sensitivity and 67.6% specificity. © 2018 by American Journal of Neuroradiology.

Genome-wide in vivo screen identifies novel host regulators of metastatic colonization

PubMed Central

van der Weyden, Louise; Arends, Mark J.; Campbell, Andrew D.; Bald, Tobias; Wardle-Jones, Hannah; Griggs, Nicola; Velasco-Herrera, Martin Del Castillo; Tüting, Thomas; Sansom, Owen J.; Karp, Natasha A.; Clare, Simon; Gleeson, Diane; Ryder, Edward; Galli, Antonella; Tuck, Elizabeth; Cambridge, Emma L.; Voet, Thierry; Macaulay, Iain C.; Wong, Kim; Spiegel, Sarah; Speak, Anneliese O.; Adams, David J.

2017-01-01

Metastasis is the leading cause of death for cancer patients. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites, then proliferate; it involves contributions from both the tumour cell and tumour microenvironment (‘host’, which includes stromal cells and the immune system1). Studies suggest the early steps of the metastatic process are relatively efficient, with the post-extravasation regulation of tumour growth (‘colonization’) being critical in determining metastatic outcome2. Here we show the results of screening 810 mutant mouse lines using an in vivo assay to identify microenvironmental regulators of metastatic colonization. We identify 23 genes that, when disrupted in mouse, modify the ability of tumour cells to establish metastatic foci, with 19 of these genes not previously demonstrated to play a role in host control of metastasis. The largest reduction in pulmonary metastasis was observed in sphingosine-1-phosphate (S1P) transporter spinster homologue 2 (Spns2)-deficient mice. We demonstrate a novel outcome of S1P-mediated regulation of lymphocyte trafficking, whereby deletion of Spns2, either globally or in a lymphatic endothelial-specific manner, creates a circulating lymphopenia and a higher percentage of effector T cells and natural killer (NK) cells present in the lung. This allows for potent tumour cell killing, and an overall decreased metastatic burden. PMID:28052056

Does IV contrast extravasation on CT in anticoagulant-related rectus sheath and iliopsoas hematoma predict hematoma expansion and patient outcomes?

PubMed

Landecy, Marie; Paquette, Brice; Revel, Lucie; Behr, Julien; Badet, Nicolas; Delabrousse, Eric

2016-11-01

The purpose of the study was to evaluate if IV contrast extravasation on CT in anticoagulant-related rectus sheath and iliopsoas hematoma predict hematoma expansion and patient outcomes. All patients presented with anticoagulation-related spontaneous IP hematoma or RS hematoma and who underwent contrast-enhanced CT exploration, with injection of a contrast material, from January 2012 to January 2015 in our institution were included in this study. Considering the retrospective nature of our study, our institutional review board judged our study to be exempted from ethical approval and no patient consent was required. Computed tomography (CT) images were retrospectively analyzed blindly of the evolution and treatment of hematomas. The type of muscle involved; the presence of contrast extravasation after contrast injection; the volume of the hematoma, as well as, clinical and biological results (hemoglobin value g/dL); and for each patient, the type of anticoagulation used, patient's treatment and outcomes were noted. The analyses were conducted using R 3.1.0. All statistical tests were 2-sided, and probability values <0.05 were regarded as significant. Sixty-eight patients were reviewed. Among 68 patients, 44 (65%) patients presented spontaneous IP hematoma and 24/68 (35%) a RS hematoma. There were 37 men (54%) and 31 (46%) women, ranging from 39 to 93 years with a median age of 75 years. Hemodynamic instability was statistically associated with IP hematomas and large volume of hematoma (p < 0.001). Only 15 patients had follow-up CT, 10 without and with IV contrast, 2 with IV contrast only, and 3 without contrast. Follow-up CT was performed from J0 to J8. Detection of contrast extravasation did not appear related to hemodynamically instability (p = 0.35), to a neurological deficit (p = 1), or to the increase in the volume of the hematoma on follow-up CT (p = 0.81). The different types of anticoagulant were not related to muscular type more than the other (p = 0.9). Among anticoagulant therapy, only vitamin K antagonist therapy was statistically associated with surgery (p = 0.04). CT extravasation of contrast material in IP and RS hematoma does not appear to be related with clinical criteria of severity, and therefore should not be solely considered as a radiological decision criteria.

Prediction of extravasation in pelvic fracture using coagulation biomarkers.

PubMed

Aoki, Makoto; Hagiwara, Shuichi; Tokue, Hiroyuki; Shibuya, Kei; Kaneko, Minoru; Murata, Masato; Nakajima, Jun; Sawada, Yusuke; Isshiki, Yuta; Ichikawa, Yumi; Oshima, Kiyohiro

2016-08-01

To evaluate the usefulness of coagulation biomarkers, which are easy and quick to analyze in emergency settings, for prediction of arterial extravasation due to pelvic fracture. The medical records of pelvic fracture patients transferred to the emergency department of Gunma University Hospital between December 2009 and May 2015 were reviewed. Patients were divided into two groups, those with (Extra(+)) and without (Extra(-)) arterial extravasation on enhanced CT or angiography. Levels of fibrin degradation products (FDP), D-dimer, fibrinogen, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, systolic blood pressure, heart rate, the Glasgow Coma Scale, pH, base excess, hemoglobin and lactate levels, the pattern of pelvic injury, and injury severity score were measured at hospital admission, and compared between the two groups. Parameters with a significant difference between the two groups were used to construct receiver operating characteristic (ROC) curves. The study included 29 patients with pelvic fracture. FDP, D-dimer, the ratio of FDP to fibrinogen and the ratio of D-dimer to fibrinogen were the most useful parameters for predicting arterial extravasation due to pelvic fracture. FDP, D-dimer, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, and hemoglobin and lactate levels were significantly higher in the Extra(+) group than in the Extra(-) group (FDP, 354.8μg/mL [median] versus 96.6μg/mL; D-dimer, 122.3μg/mL versus 42.1μg/mL; the ratio of FDP to fibrinogen, 3.39 versus 0.42; the ratio of D-dimer to fibrinogen, 1.14 versus 0.18; hemoglobin, 10.5g/dL versus 13.5g/dL; lactate, 3.5mmol/L versus 1.7mmol/L). The area under the ROC curves for FDP, D-dimer, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, hemoglobin and lactate levels were 0.900, 0.882, 0.918, 0.900, 0.815 and 0.765, respectively. Coagulation biomarkers, and hemoglobin and lactate levels could be useful to predict the existence of arterial extravasation due to pelvic fracture. The ratio of FDP to fibrinogen and the ratio of D-dimer to fibrinogen were the most accurate markers. Coagulation biomarkers may enable more rapid and specific treatment for pelvic fracture. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The plasma protein extravasation induced by adenosine and its analogues in the rat dorsal skin: evidence for the involvement of capsaicin sensitive primary afferent neurones and mast cells.

PubMed

Esquisatto, L C; Costa, S K; Camargo, E A; Ribela, M T; Brain, S D; de Nucci, G; Antunes, E

2001-09-01

1. The contribution of sensory neurons and mast cells to the oedema evoked by adenosine A1 (N(6)-cyclopentyladenosine, CPA, 3 - 30 nmol site(-1)), A2 (5'N-ethylcarboxamidoadenosine, NECA, 1 - 10 nmol site(-1)) and A3 receptor agonists (N6-[3-iodobenzyl]-N-methyl-5'-carboxiamidoadenosine, IB-MECA, 0.01 - 3 nmol site(-1)) was investigated in the rat skin microvasculature, by the extravascular accumulation of intravenously-injected (i.v.) 125I-albumin. 2. Intradermal (i.d.) injection of adenosine and analogues induced increased microvascular permeability in a dose-dependent manner (IB-MECA > NECA > CPA > adenosine). The non-selective adenosine receptor antagonist theophylline (5 - 50 nmol site(-1)) markedly inhibited adenosine, CPA or NECA but not IB-MECA-induced plasma extravasation. The A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.3 - 3 micromol kg(-1), i.v.) significantly reduced CPA-induced plasma extravasation whereas responses to adenosine, NECA or IB-MECA were unchanged. The A2 receptor antagonist 3,7-dymethyl-1-proprargylxanthine (DMPX, 0.5 - 50 nmol site(-1)) significantly reduced NECA-induced plasma extravasation without affecting responses to adenosine, CPA and IB-MECA. 3. The tachykinin NK1 receptor antagonist (S)-1-[2-[3-(3,4-dichlorphenyl)-1 (3-isopropoxyphenylacetyl) piperidin-3-yl] ethyl]-4-phenyl-1 azaniabicyclo [2.2.2]octane chloride (SR140333), but not the NK2 receptor antagonist (S)-N-methyl-N[4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]-benzamide (SR48968), significantly inhibited the plasma extravasation evoked by higher doses of adenosine (100 nmol site(-1)), CPA (100 nmol site(-1)), NECA (1 nmol site(-1)) and IB-MECA (0.1 - 1 nmol site(-1)). In rats treated with capsaicin to destroy sensory neurons, the response to higher doses of adenosine, CPA and NECA, but not IB-MECA, was significantly inhibited. 4. The effects of adenosine and analogues were largely inhibited by histamine and 5-hydroxytryptamine (5-HT) antagonists and by compound 48/80 pretreatment. 5. In conclusion, our results provide evidence that adenosine A1 and A2, but not A3, receptor agonists may function as cutaneous neurogenic pro-inflammatory mediators; acting via microvascular permeability-increasing mechanisms that can, depending on dose of agonist and purine receptor under study, involve the tachykinin NK1 receptor and mast cell amines.

Studies on the vascular permeability induced by intrathecal substance P and bradykinin in the rat.

PubMed

Jacques, L; Couture, R

1990-08-02

The effects of substance P (SP), SP fragments, neurokinin A (NKA), neurokinin B (NKB) and selective agonists for neurokinin receptors were assessed on cutaneous vascular permeability after intrathecal (i.t.) administration in rats. Dose-dependent increases in plasma extravasation were observed with the following rank orders of potency ([p-Glu6]SP-(6-11) greater than SP greater than or equal to SP-(4-11) greater than [p-Glu5,MePhe8,Sar9]SP-(5-11) = [p-Glu5]SP-(5-11) greater than SP-(7-11) and SP greater than NKA greater than NKB). The N-terminal fragments SP-(1-4), SP-(1-7) and SP-(1-9) were inactive up to 65 nmol. The NK-1 receptor selective agonists [( beta-Ala4,Sar9,Met(O2)11]SP-(4-11) and [Pro9,Met(O2)11]SP) were more potent than the NK-2 ([Nle10]NKA-(4-10] and NK-3 ([beta-Asp4,MePhe7]NKB-(4-10) and [MePhe7]NKB) receptor-selective agonists. Plasma extravasation was also increased by i.t. bradykinin (BK, 8.1 nmol) while the fragment BK-(1-8), a potent B1-receptor-selective agonist, produced only a slight effect at 81 nmol. When BK was given after prior i.t. administration of 6.1 nmol of [Thi5.8,D-Phe7]BK, an antagonist of BK at the B2-receptor, the increase in vascular permeability was significantly attenuated. The analogue [Leu8]BK-(1-8) (10.3 nmol), an antagonist of BK at the B1-receptor, failed to modify the BK-induced plasma extravasation. Plasma extravasation induced by SP (6.5 nmol) and BK (8.1 nmol) was abolished in cervically vagotomized rats, and significantly reduced in both spinal rats and in capsaicin-treated animals. Conversely, bilateral adrenalectomy (48 h earlier) and intercollicular decerebration (30 min earlier) had no major effect on the response elicited either by SP or BK. The response to SP remained unaffected by methysergide and hexamethonium but was significantly reduced by methylnitrate atropine and diphenhydramine. Indomethacin significantly enhanced the plasma extravasation induced by SP. These results suggest that SP and BK may play a role as spinal mediators in peripheral vascular permeability through a sensory and cholinergic vagal mechanism involving a spinobulbar pathway. The receptors mediating the response to SP and BK in the spinal cord are of the NK-1 and B2 subtypes, respectively.

Extravasation injuries in adults.

PubMed

Al-Benna, S; O'Boyle, C; Holley, J

2013-01-01

Insertion of an intravascular catheter is one of the most common invasive procedures in hospitals worldwide. These intravascular lines are crucial in resuscitation, allow vital medication to be administered, and can be used to monitor the patients' real-time vital parameters. There is, however, growing recognition of potential risks to life and limb associated with their use. Medical literature is now replete with isolated case reports of complications succinctly described by Garden and Laussen (2004) as "An unending supply of "unusual" complications from central venous catheters." This paper reviews complications of venous and arterial catheters and discusses treatment approaches and methods to prevent complications, based on current evidence and endeavours to provide information and guidance that will enable practitioners to prevent, recognise, and successfully treat extravasation injuries in adults.

Interstitial ion homeostasis and acid-base balance are maintained in oedematous brain of mice with acute toxic liver failure.

PubMed

Obara-Michlewska, Marta; Ding, Fengfei; Popek, Mariusz; Verkhratsky, Alexei; Nedergaard, Maiken; Zielinska, Magdalena; Albrecht, Jan

2018-05-14

Acute toxic liver failure (ATLF) rapidly leads to brain oedema and neurological decline. We evaluated the ability of ATLF-affected brain to control the ionic composition and acid-base balance of the interstitial fluid. ATLF was induced in 10-12 weeks old male C57Bl mice by single intraperitoneal (i.p.) injection of 100 μg/g azoxymethane (AOM). Analyses were carried out in cerebral cortex of precomatous mice 20-24 h after AOM administration. Brain fluid status was evaluated by measuring apparent diffusion coefficient [ADC] using NMR spectroscopy, Evans Blue extravasation, and accumulation of an intracisternally-injected fluorescent tracer. Extracellular pH ([pH] e ) and ([K + ] e ) were measured in situ with ion-sensitive microelectrodes. Cerebral cortical microdialysates were subjected to photometric analysis of extracellular potassium ([K + ] e ), sodium ([Na + ] e ) and luminometric assay of extracellular lactate ([Lac] e ). Potassium transport in cerebral cortical slices was measured ex vivo as 86 Rb uptake. Cerebral cortex of AOM-treated mice presented decreased ADC supporting the view that ATLF-induced brain oedema is primarily cytotoxic in nature. In addition, increased Evans blue extravasation indicated blood brain barrier leakage, and increased fluorescent tracer accumulation suggested impaired interstitial fluid passage. However, [K + ] e , [Na + ] e , [Lac] e , [pH] e and potassium transport in brain of AOM-treated mice was not different from control mice. We conclude that in spite of cytotoxic oedema and deregulated interstitial fluid passage, brain of mice with ATLF retains the ability to maintain interstitial ion homeostasis and acid-base balance. Tentatively, uncompromised brain ion homeostasis and acid-base balance may contribute to the relatively frequent brain function recovery and spontaneous survival rate in human patients with ATLF. Copyright © 2018. Published by Elsevier Ltd.

Plunging ranula of the submandibular area

PubMed Central

Sheikhi, Mahnaz; Jalalian, Faranak; Rashidipoor, Roghayeh; Mosavat, Farzaneh

2011-01-01

The term “ranula” is used to describe a diffuse swelling in the floor of the mouth caused by either a mucous extravasation or, less commonly, a mucous retention cyst derived from the major sublingual or submandibular salivary glands. The most common presentation of ranula is a painless, slow-growing, soft, and movable mass located in the floor of the mouth. Ranula may be simple or plunging. Simple ranula often present as masses in the floor of the mouth, limited to the mucous membranes. Diving ranulas extend through the facial plans, usually posterior to the mylohyoid muscle into the neck, and present as cervical masses. Thyroglossal duct cyst, branchial cleft cyst, cystic hygroma, submandibular sialadenitis, intramuscular hemangioma, cystic or neoplastic thyroid disease might be included in differential diagnosis. A variety of surgical procedures have been quoted in the literature ranging from marsupialization, excision of the ranula, sclerotherapy, and excision of the sublingual gland. The recurrence rate varies according to the procedure performed. PMID:23372589

Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation

PubMed Central

Wolf, Yochai; Shemer, Anat; Polonsky, Michal; Gross, Mor; Mildner, Alexander; David, Eyal; Amit, Ido; Heikenwalder, Mathias; Nedospasov, Sergei; Prinz, Marco; Friedman, Nir

2017-01-01

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function. PMID:28330904

Antiinflammatory effect of BPC 157 on experimental periodontitis in rats.

PubMed

Keremi, B; Lohinai, Z; Komora, P; Duhaj, S; Borsi, K; Jobbagy-Ovari, G; Kallo, K; Szekely, A D; Fazekas, A; Dobo-Nagy, C; Sikiric, P; Varga, G

2009-12-01

The pentadecapeptide BPC 157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. The purpose of the present study was to investigate the effect of BPC 157 on inflammation and bone resorption in experimental periodontitis in rats. First the acute effect of BPC was tested on gingival blood flow by laser doppler flowmetry. Then periodontitis was produced by a silk ligature placed around the lower left first molar. Rats were treated with BPC 157 (once daily for 12 days) or vehicle. At day 13, the gingivomucosal tissues encircling the molars were removed on both sides. Inflammation was assessed by Evans blue plasma extravasation technique and by histology. Alveolar bone loss was analyzed by microCT. BPC 157 had no effect on gingivomucosal blood flow. Twelve day ligature caused a significantly increased Evans blue extravasation in the gingivomucosal tissue, histological signs of inflammation, and alveolar bone destruction. BPC 157 treatment significantly reduced both plasma extravasation, histological alterations and alveolar bone resorption. In conclusion, systemic application of BPC 157 does not alter blood circulation in healthy gingiva. Chronic application of the peptide has potent antiinflammatory effects on periodontal tissues in ligature induced periodontitis in rats. Taken together, this proof of concept study suggests that BPC 157 may represent a new peptide candidate in the treatment of periodontal disease.

Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation

PubMed Central

Zhao, Yunge; Sharma, Ashish K.; LaPar, Damien J.; Kron, Irving L.; Ailawadi, Gorav; Liu, Yuan; Jones, David R.; Laubach, Victor E.

2011-01-01

Ischemia-reperfusion (IR) injury following lung transplantation remains a major source of early morbidity and mortality. Histologically, this inflammatory process is characterized by neutrophil infiltration and activation. We previously reported that lung IR injury was significantly attenuated in plasminogen activator inhibitor-1-deficient mice. In this study, we explored the potential role of tissue plasminogen activator (tPA) in a mouse lung IR injury model. As a result, tPA knockout (KO) mice were significantly protected from lung IR injury through several mechanisms. At the cellular level, tPA KO specifically blocked neutrophil extravasation into the interstitium, and abundant homotypic neutrophil aggregation (HNA) was detected in the lung microvasculature of tPA KO mice after IR. At the molecular level, inhibition of neutrophil extravasation was associated with reduced expression of platelet endothelial cell adhesion molecule-1 mediated through the tPA/ LDL receptor-related protein/NF-κB signaling pathway, whereas increased P-selectin triggered HNA. At the functional level, tPA KO mice incurred significantly decreased vascular permeability and improved lung function following IR. Protection from lung IR injury in tPA KO mice occurs through a fibrinolysis-independent mechanism. These results suggest that tPA could serve as an important therapeutic target for the prevention and treatment of acute IR injury after lung transplantation. PMID:21378024

In-vivo imaging of nanoshell extravasation from solid tumor vasculature by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Li, Meng-Lin; Schwartz, Jon A.; Wang, James; Stoica, George; Wang, Lihong V.

2007-02-01

In this study, high resolution reflection-mode (backward-mode) photoacoustic microscopy (PAM) is used to noninvasively image progressive extravasation and accumulation of nanoshells within a solid tumor in vivo. This study takes advantage of the strong near-infrared absorption of nanoshells, a novel type of optically tunable gold nanoparticles that tend to extravasate from leaky tumor vasculatures (i.e., passive targeting) via the "enhanced permeability and retention" effect due to their nanoscale size. Tumors were grown in immunocompetent BALB/c mice by subcutaneous inoculation of CT26.wt murine colon carcinoma cells. PEGylated nanoshells with a peak optical absorption at ~800 nm were intravenously administered. Pre-scans prior to nanoshell injection were taken using a 584-nm laser source to highlight blood content and an 800-nm laser source to mark the background limit for nanoshell accumulation. After injection, the three-dimensional nanoshell distribution inside the tumor was monitored by PAM for 7 hours. Experimental results show that nanoshell accumulation is heterogeneous in tumors: more concentrated within the tumor cortex and largely absent from the tumor core. This correlates with others' observation that drug delivery within tumor cores is ineffective because of both high interstitial pressure and tendency to necrosis of tumor cores. Since nanoshells have been recently applied to thermal therapy for subcutaneous tumors, we anticipate that PAM will be important to this therapeutic technique.

Cortactin deficiency is associated with reduced neutrophil recruitment but increased vascular permeability in vivo.

PubMed

Schnoor, Michael; Lai, Frank P L; Zarbock, Alexander; Kläver, Ruth; Polaschegg, Christian; Schulte, Dörte; Weich, Herbert A; Oelkers, J Margit; Rottner, Klemens; Vestweber, Dietmar

2011-08-01

Neutrophil extravasation and the regulation of vascular permeability require dynamic actin rearrangements in the endothelium. In this study, we analyzed in vivo whether these processes require the function of the actin nucleation-promoting factor cortactin. Basal vascular permeability for high molecular weight substances was enhanced in cortactin-deficient mice. Despite this leakiness, neutrophil extravasation in the tumor necrosis factor-stimulated cremaster was inhibited by the loss of cortactin. The permeability defect was caused by reduced levels of activated Rap1 (Ras-related protein 1) in endothelial cells and could be rescued by activating Rap1 via the guanosine triphosphatase (GTPase) exchange factor EPAC (exchange protein directly activated by cAMP). The defect in neutrophil extravasation was caused by enhanced rolling velocity and reduced adhesion in postcapillary venules. Impaired rolling interactions were linked to contributions of β(2)-integrin ligands, and firm adhesion was compromised by reduced ICAM-1 (intercellular adhesion molecule 1) clustering around neutrophils. A signaling process known to be critical for the formation of ICAM-1-enriched contact areas and for transendothelial migration, the ICAM-1-mediated activation of the GTPase RhoG was blocked in cortactin-deficient endothelial cells. Our results represent the first physiological evidence that cortactin is crucial for orchestrating the molecular events leading to proper endothelial barrier function and leukocyte recruitment in vivo.

Rôle of contrast media viscosity in altering vessel wall shear stress and relation to the risk of contrast extravasations.

PubMed

Sakellariou, Sophia; Li, Wenguang; Paul, Manosh C; Roditi, Giles

2016-12-01

Iodinated contrast media (CM) are the most commonly used injectables in radiology today. A range of different media are commercially available, combining various physical and chemical characteristics (ionic state, osmolality, viscosity) and thus exhibiting distinct in vivo behaviour and safety profiles. In this paper, numerical simulations of blood flow with contrast media were conducted to investigate the effects of contrast viscosity on generated vessel wall shear stress and vessel wall pressure to elucidate any possible relation to extravasations. Five different types of contrast for Iodine fluxes ranging at 1.5-2.2gI/s were modelled through 18G and 20G cannulae placed in an ideal vein at two different orientation angles. Results demonstrate that the least viscous contrast media generate the least maximum wall shear stress as well as the lowest total pressure for the same flow rate. This supports the empirical clinical observations and hypothesis that more viscous contrast media are responsible for a higher percentage of contrast extravasations. In addition, results support the clinical hypothesis that a catheter tip directed obliquely to the vein wall always produces the highest maximum wall shear stress and total pressure due to impingement of the contrast jet on the vessel wall. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Fibrin, γ’-fibrinogen, and trans-clot pressure gradient control hemostatic clot growth during human blood flow over a collagen/tissue factor wound

PubMed Central

Muthard, Ryan W.; Welsh, John D.; Brass, Lawrence F.; Diamond, Scott L.

2015-01-01

SUMMARY Objective Biological and physical factors interact to modulate blood response in a wounded vessel, resulting in a hemostatic clot or an occlusive thrombus. Flow and pressure differential (ΔP) across the wound from the lumen to the extravascular compartment may impact hemostasis and the observed core/shell architecture. We examined physical and biological factors responsible for regulating thrombin mediated clot growth. Approach and Results Using factor XIIa-inhibited human whole blood perfused in a microfluidic device over collagen/tissue factor at controlled wall shear rate and ΔP, we found thrombin to be highly localized in the P-selectin+ core of hemostatic clots. Increasing ΔP from 9 to 29 mm-Hg (wall shear rate = 400 s−1) reduced P-selectin+ core size and total clot size due to enhanced extravasation of thrombin. Blockade of fibrin polymerization with 5 mM GPRP dysregulated hemostasis by enhancing both P-selectin+ core size and clot size at 400 s−1 (20 mm-Hg). For whole blood flow (no GPRP), the thickness of the P-selectin-negative shell was reduced under arterial conditions (2000 s−1, 20 mm-Hg). Consistent with the antithrombin-1 activity of fibrin implicated with GPRP, anti-γ’-fibrinogen antibody enhanced core-localized thrombin, core size, and overall clot size, especially at venous (100 s−1) but not arterial wall shear rates (2000 s−1). Pathological shear (15,000 s−1) and GPRP synergized to exacerbate clot growth. Conclusions Hemostatic clotting was dependent on core-localized thrombin that (1) triggered platelet P-selectin display and (2) was highly regulated by fibrin and the trans-clot ΔP. Also, γ’-fibrinogen had a role in venous but not arterial conditions. PMID:25614284

Cutaneous and subcutaneous complications of calcium infusions.

PubMed

Roberts, J R

1977-01-01

Five infants with hypocalcemia experienced complications after treatment with calcium gluconate intravenously. Inadvertent soft tissue extravasation resulted in erythema, subcutaneous calcification, tissue necrosis, skin slough, and transient radial nerve damage with wrist drop, the latter previously unreported. The soft tissue lesions may be mistaken for cellulitis, abscess, calcified hematoma, or osteomyelitis, resulting in unnecessary antibiotic therapy or surgical intervention. Initially, no clinical abnormality may be apparent. The lesions appear from days to weeks following extravasation. Radiographs are initially negative but soft calcification appears in one to three weeks. Follow-up x-ray films show complete resorption of the calcium over several months. Skin sloughs heal in four to six weeks without skin grafting. Extreme care in the parenteral use of calcium gluconate and conservative treatment of the complications is advocated.

Technetium-99m labeled red blood cells in the evaluation of hemangiosarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joseph, U.A.; Jhingran, S.G.

Imaging with Tc-99m labeled red blood cells (RBC) is increasingly being used in the detection of acute gastro-intestinal bleeding, especially in patients with intermittent bleeding. A patient is presented in whom the labeled RBC scan was helpful in the incidental discovery of a previously unsuspected probable angiosarcoma of the right femur and adjacent soft tissues of the right hip due to the blood pool or blush effect of the labeled cells. The labeled RBC scan also identified extravasation due to active gastrointestinal bleeding from a previously unknown angiosarcoma of the ascending colon. Thus, the Tc-99m labeled RBC scan was usefulmore » in simultaneously detecting extravasation and blood pool effect at two remote tumor sites in the same patient.« less

In situ FTIR microspectroscopy of extravasated blood-damaged brain tissue

NASA Astrophysics Data System (ADS)

Wetzel, David L.; Le Vine, Steven M.

1994-01-01

Fourier transform infrared (FT-IR) microspectroscopy enables the collection of infrared spectra from microscopic regions of tissue sections. The objectives of this study were to utilize FT-IR microspectroscopy to analyze the spatial distribution of chemical changes that result from the extravasation of blood into the brain and to determine if products of free radical damage are associated with the damaged areas. An animal model that involves the injection of blood into the white matter of rat brains was used. Maps depicting the relative concentrations of chemical functional groups of lesioned sites and surrounding areas were made. Significant decreases were observed for CH2, C equals O, P equals O, and HO-C-H functional groups at the lesioned site and penumbra regions compared to the neighboring normal tissue areas.

Hemidiaphragmatic paralysis in preterm neonates: a rare complication of peripherally inserted central catheter extravasation.

PubMed

Tosello, Barthelemy; Michel, Fabrice; Merrot, Thierry; Chaumoître, Kathia; Hassid, Sophie; Lagier, Pierre; Martin, Claude

2011-07-01

Unilateral diaphragmatic paralysis was diagnosed in 2 preterm neonates born at 29 and 25 weeks of gestation, respectively. In both instances, the pathophysiology was phrenic nerve injury after extravasation of parenteral nutrition fluid. Misplacement and infection were predisposing factors. Diaphragmatic movement analysis by time-motion-mode ultrasonography was helpful in achieving a diagnosis. The first neonate required a diaphragmatic placation, whereas the other infant was managed nonoperatively. These cases confirm a rare etiology of diaphragmatic paralysis and possible spontaneous recovery. In neonates with very low birth weight, general anesthesia and thoracic surgery may be associated with a high morbidity, suggesting that nonoperative medical treatment, when possible, is preferable if the neonate does not require supplemental oxygen. Copyright © 2011 Elsevier Inc. All rights reserved.

Extravasation Injuries in Adults

PubMed Central

Al-Benna, S.; O'Boyle, C.; Holley, J.

2013-01-01

Insertion of an intravascular catheter is one of the most common invasive procedures in hospitals worldwide. These intravascular lines are crucial in resuscitation, allow vital medication to be administered, and can be used to monitor the patients' real-time vital parameters. There is, however, growing recognition of potential risks to life and limb associated with their use. Medical literature is now replete with isolated case reports of complications succinctly described by Garden and Laussen (2004) as “An unending supply of “unusual” complications from central venous catheters.” This paper reviews complications of venous and arterial catheters and discusses treatment approaches and methods to prevent complications, based on current evidence and endeavours to provide information and guidance that will enable practitioners to prevent, recognise, and successfully treat extravasation injuries in adults. PMID:23738141

Use of an angiographic catheter to facilitate fluoroscopy-guided percutaneous renal access in cases with diffuse contrast extravasation.

PubMed

Giannakopoulos, Stilianos; Bantis, Athanasios; Kalaitzis, Christos; Touloupidis, Stavros

2010-10-01

Occasionally during percutaneous surgery, significant contrast extravasation obscures the field, making fluoroscopic access no longer feasible. Herein, we describe a salvage technique. The cystoscopically placed, open-end ureteral catheter is exchanged with an angled-tip angiographic catheter. With the aid of a guidewire and under fluoroscopic guidance, the tip of the catheter is placed in a posterior calix. The "bull's eye" technique is then applied to direct the needle into the tip of the catheter. This technique was used in four cases over a 7-year period. Successful access was accomplished in all cases through a middle or upper calix. The catheter serves as a target for providing access to the renal collecting system and facilitates final tract dilatation.

Adoptive transfer of acute lung injury.

PubMed

Moxley, M A; Baird, T L; Corbett, J A

2000-11-01

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.

Blood-brain barrier dysfunction and cerebral small vessel disease (arteriolosclerosis) in brains of older people.

PubMed

Bridges, Leslie R; Andoh, Joycelyn; Lawrence, Andrew J; Khoong, Cheryl H L; Poon, Wayne; Esiri, Margaret M; Markus, Hugh S; Hainsworth, Atticus H

2014-11-01

The blood-brain barrier protects brain tissue from potentially harmful plasma components. Small vessel disease (SVD; also termed arteriolosclerosis) is common in the brains of older people and is associated with lacunar infarcts, leukoaraiosis, and vascular dementia. To determine whether plasma extravasation is associated with SVD, we immunolabeled the plasma proteins fibrinogen and immunoglobulin G, which are assumed to reflect blood-brain barrier dysfunction, in deep gray matter (DGM; anterior caudate-putamen) and deep subcortical white matter (DWM) in the brains of a well-characterized cohort of donated brains with minimal Alzheimer disease pathology (Braak Stages 0-II) (n = 84; aged 65 years or older). Morphometric measures of fibrinogen labeling were compared between people with neuropathologically defined SVD and aged control subjects. Parenchymal cellular labeling with fibrinogen and immunoglobulin G was detectable in DGM and DWM in many subjects (>70%). Quantitative measures of fibrinogen were not associated with SVD in DGM or DWM; SVD severity was correlated between DGM and DWM (p < 0.0001). Fibrinogen in DGM showed a modest association with a history of hypertension; DWM fibrinogen was associated with dementia and cerebral amyloid angiopathy (all p < 0.05). In DWM, SVD was associated with leukoaraiosis identified in life (p < 0.05), but fibrinogen was not. Our data suggest that, in aged brains, plasma extravasation and hence local blood-brain barrier dysfunction are common but do not support an association with SVD.

Role of central versus peripheral opioid system in antinociceptive and anti-inflammatory effect of botulinum toxin type A in trigeminal region.

PubMed

Drinovac Vlah, V; Filipović, B; Bach-Rojecky, L; Lacković, Z

2018-03-01

Although botulinum toxin type A (BT-A) is approved for chronic migraine treatment, its site and mechanism of action are still elusive. Recently our group discovered that suppression of CGRP release from dural nerve endings might account for antimigraine action of pericranially injected BT-A. We demonstrated that central antinociceptive effect of BT-A in sciatic region involves endogenous opioid system as well. Here we investigated possible interaction of BT-A with endogenous opioid system within the trigeminal region. In orofacial formalin test we investigated the influence of centrally acting opioid antagonist naltrexone (2 mg/kg, s.c.) versus peripherally acting methylnaltrexone (2 mg/kg, s.c.) on BT-A's (5 U/kg, s.c. into whisker pad) or morphine's (6 mg/kg, s.c.) antinociceptive effect and the effect on dural neurogenic inflammation (DNI). DNI was assessed by Evans blue-plasma protein extravasation. Naltrexone abolished the effect of BT-A on pain and dural plasma protein extravasation, whereas peripherally acting methylnaltrexone did not change either BT-A's effect on pain or its effect on dural extravasation. Naltrexone abolished the antinociceptive and anti-inflammatory effects of morphine, as well. However, methylnaltrexone decreased the antinociceptive effect of morphine only partially in the second phase of the test and had no significant effect on morphine-mediated reduction in DNI. Morphine acts on pain in trigeminal region both peripherally and centrally, whereas the effect on dural plasma protein extravasation seems to be only centrally mediated. However, the interaction of BT-A with endogenous opioid system, with consequent inhibition of nociceptive transmission as well as the DNI, occurs primarily centrally. Botulinum toxin type A (BT-A)'s axonal transport and potential transcytosis suggest that its antinociceptive effect might involve diverse neurotransmitters at different sites of trigeminal system. Here we discovered that the reduction in pain and accompanying DNI involves the interaction of BT-A with central endogenous opioid system (probably at the level of trigeminal nucleus caudalis). © 2017 European Pain Federation - EFIC®.

Limits of intravascular contrast extravasation on computed tomography scan to define the need for pelvic angioembolization in pelvic blunt trauma: a specific assessment on the risk of false-positives.

PubMed

Ramin, Séverin; Hermida, Margaux; Millet, Ingrid; Murez, Thibault; Monnin, Valérie; Hamoui, Mazen; Capdevila, Xavier; Charbit, Jonathan

2018-06-12

The objective was to assess the predictive performance of different intravascular contrast extravasation (ICE) characteristics for need for pelvic transarterial embolization (TAE) to determine the risk factors of false-positives. A retrospective study was performed in our trauma center between 2010 and 2015. All severe trauma patients with pelvic fracture were included. Pelvic ICE characteristics on computed tomography (CT) scan were studied: arterial (aSICE), portal surface (pSICE), and extension (exSICE) anatomic relationships. The overall predictive performance of ICE surfaces for pelvic TAE was analyzed using receiver operating characteristic curves. The analysis focused on risk factors for false-positives. Among 311 severe trauma patients with pelvic ring fracture (mean age, 42 ± 19 years, mean Injury Severity Score, 27 ± 19), 94 (30%) had at least one pelvic ICE on the initial CT scan. Patients requiring pelvic TAE had significantly larger aSICE and pSICE than others (P=0.001 and P=0.035, respectively). The overall ability of ICE surfaces to predict pelvic TAE was modest (aSICE AUC, 0.76 [95% CI, 0.64-0.90]; P=0.011) or non-significant (pSICE and exSICE). The high-sensitivity threshold was defined as aSICE ≥20 mm. Using this threshold, 76% of patients were false-positives. Risk factors for false-positives were: admission systolic blood pressure ≥90 mmHg (63% versus 20%; P=0.03) and low transfusion needs (63% versus 10%; P=0.009), extravasation in contact with complex bone fracture (78% versus 30%; P=0.008) or the absence of a direct relationship between extravasation and a large retroperitoneal hematoma (100% versus 38%; P<0.001). A significant pelvic ICE during the arterial phase does not guarantee the need for pelvic TAE. Three-quarter of patients with aSICE ≥20 mm did not need pelvic TAE. Several complementary CT scan criteria will help to identify this risk of false-positives to determine adequate hemostatic pelvic procedures.This work is an original article, retrospective study Level II of evidence, Therapeutic/Critical Care management.

Epidural spinal cord compression with neurologic deficit associated with intrapedicular application of hemostatic gelatin matrix during pedicle screw insertion.

PubMed

Buchowski, Jacob M; Bridwell, Keith H; Lenke, Lawrence G; Good, Christopher R

2009-06-01

Case report. In order to demonstrate the dangers of intrapedicular application of a hemostatic gelatin matrix to decrease blood loss during pedicle screw insertion, we present 2 patients who--as a result of inadvertent extravasation of the matrix into the spinal canal--developed epidural spinal cord compression (ESCC) requiring emergent decompression. Variety of hemostatic agents can control bleeding during pedicle screw insertion. We have often used a hemostatic gelatin matrix to decrease bleeding from cannulated pedicles by injecting the material into the pedicle after manually palpating the pedicle. Medical records and radiographic studies of 2 patients with AIS who underwent surgical treatment of their deformity and developed a neurologic deficit due to extravasation of FloSeal were reviewed. A 15 year-old male underwent T4 to L2 posterior spinal fusion (PSF). During pedicle screw insertion, a change in NMEPs and SSEPs was noted. A wake-up test confirmed bilateral LE paraplegia. Screws were removed and no perforations were noted on manual palpation. MRI showed T7 to T10 ESCC. He underwent a T5 to T10 laminectomy and hemostatic gelatin matrix noted in the canal and was evacuated. He was ambulatory at 2 weeks and by 3 months he had complete recovery. The second patient was a 15 year-old female who underwent T4 to L1 PSF. Following screw insertion, deterioration in NMEPs and SSEPs was noted. Screws were removed and SCM data returned to baseline. Except for 3 screws that had an inferior breach (Left T7 and Bilateral T8), screws were reinserted and remainder of the surgery was uneventful. Postoperative examination was normal initially but 2 days later, she developed left LE numbness/weakness. Implants were removed and MRI showed T4 to T9 ESCC.She underwent a left (concave) T4 to T9 hemilaminectomy. Hemostatic gelatin matrix was noted and was evacuated. Six weeks following surgery, she had a complete neurologic recovery. The use of a hemostatic gelatin matrix to decrease bleeding from cannulated pedicles during pedicle screw insertion can result in inadvertent extravasation into the spinal canal resulting in ESCC even in the absence of an apparent medial pedicle breach. Given the dangers associated with the technique, we recommend that gelatin matrix products be used judiciously during pedicle screw insertion.

Presence of Laminin Receptors in Staphylococcus aureus

NASA Astrophysics Data System (ADS)

Lopes, J. D.; Dos Reis, M.; Brentani, R. R.

1985-07-01

A characteristic feature of infection by Staphylococcus aureus is bloodstream invasion and widespread metastatic abscess formation. The ability to extravasate, which entails crossing the vascular basement membrane, appears to be critical for the organism's pathogenicity. Extravasation by normal and neoplastic mammalian cells has been correlated with the presence of specific cell surface receptors for the basement membrane glycoprotein laminin. Similar laminin receptors were found in Staphylococcus aureus but not in Staphylococcus epidermidis, a noninvasive pathogen. There were about 100 binding sites per cell, with an apparent binding affinity of 2.9 nanomolar. The molecular weight of the receptor was 50,000 and pI was 4.2. Eukaryotic laminin receptors were visualized by means of the binding of S. aureus in the presence of laminin. Prokaryotic and eukaryotic invasive cells might utilize similar, if not identical, mechanisms for invasion.

Recanalization after successful occlusion by transcatheter arterial embolization with N-butyl cyanoacrylate for traumatic splenic artery injury.

PubMed

Ishikawa, Masaki; Kakizawa, Hideaki; Yamasaki, Wataru; Date, Syuji; Hieda, Masashi; Kajiwara, Kenji; Awai, Kazuo

2011-12-01

A 70-year-old male with advanced pancreatic cancer went into shock after sustaining a traumatic abdominal injury. Computed tomography (CT) showed a hematoma with extravasation around the pancreas and hemorrhagic ascites. After direct catheterization failed due to angiospasm, the ruptured splenic artery was successfully occluded by transcatheter arterial embolization (TAE) using an N-butyl cyanoacrylate (NBCA)-lipiodol mixture and the patient recovered from shock without complications. A follow-up CT obtained 20 days later showed a recurrent splenic artery pseudoaneurysm without extravasation. A repeat angiogram demonstrated recanalization of the splenic artery and pseudoaneurysm via antegrade. We embolized the recanalized pseudoaneurysm using metallic coils for isolation. Our experience indicates that adequate concentration and volume of the NBCA-lipiodol mixture should be considered depending on the vascular spasm in a patient with hypovolemic shock.

A clinicopathologic review of 138 cases of mucoceles in a pediatric population.

PubMed

Martins-Filho, Paulo Ricardo Saquete; Santos, Thiago de Santana; da Silva, Heitor Fontes; Piva, Marta Rabello; Andrade, Emanuel Sávio de Souza; da Silva, Luiz Carlos Ferreira

2011-09-01

To evaluate the clinicopathologic features of pediatric mucoceles diagnosed in two public institutions in Brazil during an 18-year period. Clinical data (age, sex, history of trauma, location, and size) of 138 cases of mucoceles in children 0 to 16 years of age were obtained from medical records. The lesions were classified as mucus extravasation phenomenon and mucus retention phenomenon, depending on the presence of epithelial lining in the microscopic analysis. Mucoceles made up 24.5% of the oral pediatric lesions diagnosed in the period of study. Age at diagnosis ranged from 0.4 to 16.0 years, with a mean age of 10.8 years. Of the total of mucoceles, 87 were observed in females and 51 in males. The lower lip was the most commonly affected site, and a history of trauma was related by 87% of the patients. Histologically, 96.4% of mucoceles were diagnosed as mucus extravasation phenomenon. Cases of mucus retention phenomenon were relatively more common in the floor of the mouth, since one in three lesions in this location belonged to this histologic type. Regarding lesions in the lower lip, only 2.65% were diagnosed as mucus retention phenomenon. Trauma is the main etiologic factor involved in the development of mucoceles in children. The mucus extravasation phenomenon is the most common histologic type in this age group. Although rare, the retention type seems to be more common in lesions on the floor of the mouth.

Dermatological toxicity in women with breast cancer undergoing chemotherapy treatment.

PubMed

Gozzo, Thais de Oliveira; Panobianco, Marislei Sanches; Clapis, Maria José; de Almeida, Ana Maria

2010-01-01

This study aimed to analyze the occurrence of skin toxicity caused by drugs used in the protocol of neoadjuvant and adjuvant chemotherapy among women with breast cancer. Patient records of 72 women who were subject to this therapy between 2003 and 2006 were assessed. Of the 558 cycles of chemotherapy, 152 adverse events were registered. There were 37 registrations of dermatological toxicity, of those, 20 were extravasations that affected 17 women. Nine reports of hardened local injury, local fibrosis, pain, and hyperemia were registered during neoadjuvancy. In adjuvancy, among the 11 extravasations registered there were reports of hardened local injury, fibrosis and local pain. Lack of follow-up records for both periods was observed. Registration of the events and reports by the nursing team are essential to monitor the sites of venous puncture during the chemotherapy treatment, besides measuring and making a photographic record of the site.

Fluorescein isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability

PubMed Central

Natarajan, Reka; Northrop, Nicole

2017-01-01

The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. PMID:28398646

Successful management of severe blunt hepatic trauma by angiographic embolization.

PubMed

Kanakis, Meletios A; Thomas, Theodoros; Martinakis, Vassilios G; Brountzos, Elias; Varsamidakis, Nicholas

2012-12-01

We present the case of an 18-year-old female with severe liver trauma after a motorcycle accident. Due to initial hemodynamic instability, fluid resuscitation and transfusion of two units of red packed cells was required. After stabilization, a CT scan was performed, showing grade V liver injuries according to the American Association for the Surgery of Trauma grading system. Angiography revealed multiple extravasations during the early arterial phase, as well as active extravasation from the proximal left hepatic artery in the late arterial phase. The patient was successfully treated by arterial embolization using metal microcoils, after which no further need for blood transfusion ensued. This report highlights that, in carefully selected cases, arterial embolization can improve the clinical condition of patients, reduce the need for blood transfusion and lessen the possibility of an operation, even if severe liver trauma has ensued.

Mononuclear cells in the corneal response to endotoxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howes, E.L.; Cruse, V.K.; Kwok, M.T.

A severe keratitis can be produced after the direct injection of bacterial endotoxin, or lipopolysaccharide (LPS), in rabbits. Corneal inflammation can progress to scarring and vascularization within a 2 to 3 week period. Pretreatment with systemic adrenal corticosteroids (triamcinolone) prevents this response. Limbal cellular and vascular events were studied during the first 20 hr after injection of LPS in treated and nontreated rabbits. Perivascular limbal inflammatory cells were counted and limbal vascular permeability was assessed by extravasation of 131I-albumin and 125I-fibrinogen in the cornea. Corticosteroids decreased but did not prevent the early protein extravasation and profoundly altered the inflammatory cellmore » population around blood vessels at the limbus. Mononuclear cells, particularly mononuclear phagocytes, were sharply reduced. It is proposed that these cell types play an important role in the perpetuation and amplification of the inflammatory response in this reaction.« less

Structure of solid tumors and their vasculature: Implications for therapy with monoclonal antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dvorak, H.F.; Nagy, J.A.; Dvorak, A.M.

Delivery of monoclonal antibodies to solid tumors is a vexing problem that must be solved if these antibodies are to realize their promise in therapy. Such success as has been achieved with monoclonal antibodies is attributable to the local hyperpermeability of the tumor vasculature, a property that favors antibody extravasation at tumor sites and that is mediated by a tumor-secreted vascular permeability factor. However, leaky tumor blood vessels are generally some distance removed from target tumor cells, separated by stroma and by other tumor cells that together represent significant barriers to penetration by extravasated monoclonal antibodies. For this reason, alternativemore » approaches may be attractive. These include the use of antibody-linked cytotoxins, which are able to kill tumor cells without immediate contact, and direction of antibodies against nontumor cell targets, for example, antigens unique to the tumor vascular endothelium or to tumor stroma. 50 refs.« less

Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases.

PubMed

Wilhelm, Imola; Fazakas, Csilla; Molnár, Kinga; Végh, Attila G; Haskó, János; Krizbai, István A

2018-04-01

Despite the potential obstacle represented by the blood-brain barrier for extravasating malignant cells, metastases are more frequent than primary tumors in the central nervous system. Not only tightly interconnected endothelial cells can hinder metastasis formation, other cells of the brain microenvironment (like astrocytes and microglia) can also be very hostile, destroying the large majority of metastatic cells. However, malignant cells that are able to overcome these harmful mechanisms may benefit from the shielding and even support provided by cerebral endothelial cells, astrocytes and microglia, rendering the brain a sanctuary site against anti-tumor strategies. Thus, cells of the neurovascular unit have a Janus-faced attitude towards brain metastatic cells, being both destructive and protective. In this review, we present the main mechanisms of brain metastasis formation, including those involved in extravasation through the brain vasculature and survival in the cerebral environment.

A rare cause of lateral facial swelling.

PubMed

Mohanty, Sujata; Gulati, Ujjwal; Vandana; Singh, Sapna

2014-01-01

A case of chronic, recurrent and asymptomatic facial swelling in a young male is presented. Swelling extended from lower midface to upper lateral neck and right commissure to anterior massetric border. History, clinical signs and symptoms and examination pointed towards the benign nature of the swelling. Fine-needle aspiration cytology tapered the diagnostic possibilities to a salivary cyst or pseudocyst. Ultrasonography identified the lesion to contain echogenic fluid with irregular borders. "Tail sign" was absent on contrast magnetic resonance imaging, excluding the involvement of the sublingual gland. Surgical excision of the lesion was done along with submandibular gland as both were in continuity via a bottle-neck tract. Final histopathological diagnosis was that of the submandibular gland extravasation phenomenon. As per the best of our knowledge, it is the first case report of a submandibular gland extravasation causing swelling in a retrograde direction onto the face.

A rare cause of lateral facial swelling

PubMed Central

Mohanty, Sujata; Gulati, Ujjwal; Vandana; Singh, Sapna

2014-01-01

A case of chronic, recurrent and asymptomatic facial swelling in a young male is presented. Swelling extended from lower midface to upper lateral neck and right commissure to anterior massetric border. History, clinical signs and symptoms and examination pointed towards the benign nature of the swelling. Fine-needle aspiration cytology tapered the diagnostic possibilities to a salivary cyst or pseudocyst. Ultrasonography identified the lesion to contain echogenic fluid with irregular borders. “Tail sign” was absent on contrast magnetic resonance imaging, excluding the involvement of the sublingual gland. Surgical excision of the lesion was done along with submandibular gland as both were in continuity via a bottle-neck tract. Final histopathological diagnosis was that of the submandibular gland extravasation phenomenon. As per the best of our knowledge, it is the first case report of a submandibular gland extravasation causing swelling in a retrograde direction onto the face. PMID:25593883

Diabetes-induced microvascular complications at the level of the spinal cord; a contributing factor in diabetic neuropathic pain.

PubMed

Ved, N; Da Vitoria Lobo, M E; Bestall, S M; L Vidueira, C; Beazley-Long, N; Ballmer-Hofer, K; Hirashima, M; Bates, D O; Donaldson, L F; Hulse, R P

2018-05-17

Abnormalities of neurovascular interactions within the central nervous system of diabetic patients is associated with the onset of many neurological disease states. However, to date, the link between the neurovascular network within the spinal cord and regulation of nociception has not been investigated despite neuropathic pain being common in diabetes. We hypothesised that hyperglycaemia-induced endothelial degeneration in the spinal cord, due to suppression of VEGF-A/VEGFR2 signalling, induces diabetic neuropathic pain. Nociceptive pain behaviour was investigated in a chemically induced model of type 1 diabetes (streptozotocin induced, insulin supplemented; either vehicle or VEGF-A 165 b treated) and an inducible endothelial knockdown of VEGFR2 (tamoxifen induced). Diabetic animals developed mechanical allodynia and heat hyperalgesia. This was associated with a reduction in the number of blood vessels and reduction in Evans blue extravasation in the lumbar spinal cord of diabetic animals versus age-matched controls. Endothelial markers occludin, CD31 and VE-cadherin were downregulated in the spinal cord of the diabetic group versus controls, as well as a concurrent reduction of VEGF-A 165 b expression. In diabetic animals, VEGF-A 165 b treatment (biweekly intraperitoneal, 20 ng g -1 ) restored normal Evans blue extravasation and prevented vascular degeneration, diabetes-induced central neuron activation and neuropathic pain. Inducible knockdown of VEGFR2 (tamoxifen treated Tie2CreER T2 -vegfr2 flfl mice) led to a reduction in blood vessel network volume in the lumbar spinal cord and development of heat hyperalgesia. These findings indicate that hyperglycaemia leads to a reduction in the VEGF-A/VEGFR2 signalling cascade resulting in endothelial dysfunction in the spinal cord, which could be an undiscovered contributing factor to diabetic neuropathic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The spot sign and tranexamic acid on preventing ICH growth--AUStralasia Trial (STOP-AUST): protocol of a phase II randomized, placebo-controlled, double-blind, multicenter trial.

PubMed

Meretoja, Atte; Churilov, Leonid; Campbell, Bruce C V; Aviv, Richard I; Yassi, Nawaf; Barras, Christen; Mitchell, Peter; Yan, Bernard; Nandurkar, Harshal; Bladin, Christopher; Wijeratne, Tissa; Spratt, Neil J; Jannes, Jim; Sturm, Jonathan; Rupasinghe, Jayantha; Zavala, Jorge; Lee, Andrew; Kleinig, Timothy; Markus, Romesh; Delcourt, Candice; Mahant, Neil; Parsons, Mark W; Levi, Christopher; Anderson, Craig S; Donnan, Geoffrey A; Davis, Stephen M

2014-06-01

No evidence-based acute therapies exist for intracerebral hemorrhage. Intracerebral hemorrhage growth is an important determinant of patient outcome. Tranexamic acid is known to reduce hemorrhage in other conditions. The study aims to test the hypothesis that intracerebral hemorrhage patients selected with computed tomography angiography contrast extravasation 'spot sign' will have lower rates of hematoma growth when treated with intravenous tranexamic acid within 4.5-hours of stroke onset compared with placebo. The Spot sign and Tranexamic acid On Preventing ICH growth--AUStralasia Trial is a multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled, investigator-initiated, academic Phase II trial. Intracerebral hemorrhage patients fulfilling clinical criteria (e.g. Glasgow Coma Scale >7, intracerebral hemorrhage volume <70 ml, no identified secondary cause of intracerebral hemorrhage, no thrombotic events within the previous 12 months, no planned surgery) and demonstrating contrast extravasation on computed tomography angiography will receive either intravenous tranexamic acid 1 g 10-min bolus followed by 1 g eight-hour infusion or placebo. A second computed tomography will be performed at 24 ± 3 hours to evaluate intracerebral hemorrhage growth and patients followed up for three-months. The primary outcome measure is presence of intracerebral hemorrhage growth by 24 ± 3 hours, defined as either >33% or >6 ml increase from baseline, and will be adjusted for baseline intracerebral hemorrhage volume. Secondary outcome measures include growth as a continuous measure, thromboembolic events, and the three-month modified Rankin Scale score. This is the first trial to evaluate the efficacy of tranexamic acid in intracerebral hemorrhage patients selected based on an imaging biomarker of high likelihood of hematoma growth. The trial is registered as NCT01702636. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Evaluating abdominal oedema during experimental sepsis using an isotope technique.

PubMed

Lattuada, Marco; Maripuu, Enn; Segerstad, Carl Hard af; Lundqvist, Hans; Hedenstierna, Göran

2012-05-01

Abdominal oedema is common in sepsis. A technique for the study of such oedema may guide in the fluid regime of these patients. We modified a double-isotope technique to evaluate abdominal organ oedema and fluid extravasation in 24 healthy or endotoxin-exposed ('septic') piglets. Two different markers were used: red blood cells (RBC) labelled with Technetium-99m ((99m)Tc) and Transferrin labelled with Indium111 ((111)In). Images were acquired on a dual-head gamma camera. Microscopic evaluation of tissue biopsies was performed to compare data with the isotope technique. No (99m)Tc activity was measured in the plasma fraction in blood sampled after labelling. Similarly, after molecular size gel chromatography, (111)In activity was exclusively found in the high molecular fraction of the plasma. Extravasation of transferrin, indicating the degree of abdominal oedema, was 4·06 times higher in the LPS group compared to the healthy controls (P<0·0001). Abdominal free fluid, studied in 3 animals, had as high (111)In activity as in plasma, but no (99m)Tc activity. Intestinal lymphatic vessel size was higher in LPS (3·7 ± 1·1 μm) compared to control animals (0·6 + 0·2 μm; P<0·001) and oedema correlated to villus diameter (R(2) = 0·918) and lymphatic diameter (R(2) = 0·758). A correlation between a normalized index of oedema formation (NI) and intra-abdominal pressure (IAP) was also found: NI = 0·46*IAP-3·3 (R(2) = 0·56). The technique enables almost continuous recording of abdominal oedema formation and may be a valuable tool in experimental research, with the potential to be applied in the clinic. © 2011 The Authors. Clinical Physiology and Functional Imaging © 2011 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Embolization for Thoracic Duct Collateral Leakage in High-Output Chylothorax After Thoracic Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kariya, Shuji, E-mail: kariyas@hirakata.kmu.ac.jp; Nakatani, Miyuki, E-mail: nakatanm@hirakata.kmu.ac.jp; Yoshida, Rie, E-mail: yagir@hirakata.kmu.ac.jp

PurposeThis study was designed to investigate thoracic duct collateral leakage and the supply route of lymphatic fluid by lymphangiography and transcatheter thoracic ductography and to evaluate the results of embolization for thoracic duct collateral leakage performed to cut off this supply route.MethodsData were retrospectively collected from five patients who underwent embolization for thoracic duct collateral leakage in persistent high-output chylothorax after thoracic surgery. Extravasation of lipiodol at the ruptured thoracic duct collaterals was confirmed in all patients on lymphangiography. Transcatheter thoracic ductography was used to identify extravasation of iodinated contrast agent and to identify communication between the thoracic duct andmore » leakage site. Thoracic duct embolization (TDE) was performed using the percutaneous transabdominal approach to cut off the supply route using N-butyl cyanoacrylate (NBCA) mixed with lipiodol (1:5–1:20).ResultsClinical success (drainage volume ≤10 mL/kg/day within 7 days after TDE) was achieved in all patients. The collateral routes developed as consequence of surgical thoracic duct ligation. In three patients, NBCA-Lipiodol reached the leakage site through direct communication between the thoracic duct and the ruptured lymphatic duct. In the other two patients, direct communication and extravasation was not detected on thoracic ductography, and NBCA-Lipiodol did not reach the leakage site. However, NBCA-Lipiodol did reach the cisterna chyli, lumbar trunks, and some collateral routes via the cisterna chyli or lumbar lymphatics. As a result, leakage was stopped.ConclusionsTDE was effective for the management of leakage of the collaterals in high-output chylothorax after thoracic surgery.« less

Improving Pediatric Adverse Drug Event Reporting through Clinical Pharmacy Services

PubMed Central

Crowther, David M.; Buck, Marcia L.; McCarthy, Michelle W.; Barton, Virginia W.

2011-01-01

OBJECTIVES The purpose of this study was to summarize adverse drug event (ADE) reporting and to characterize the type of healthcare practitioners involved in reporting over a 10-year period at a 120-bed university-affiliated children's hospital. METHODS The University of Virginia Children's Hospital ADE database was analyzed for records involving pediatric patients. Data from patients <18 years of age who were admitted to the University of Virginia Children's Hospital between January 1, 2000, and December 31, 2009, were analyzed. Data collected included drug name and therapeutic class of the suspected causative agent, description of the event, severity, causality, outcome, and the type of healthcare practitioner reporting the event. RESULTS A total of 863 ADEs were reported over the 10-year period. The 5 most common types reported were extravasation injury (10%), rash (8%), hypotension (5%), pruritus (5%), and renal failure (3%). A total of 196 (21%) cases were categorized as mild, 436 (47%) cases as moderate, and 296 (32%) cases as severe. Further characterization of extravasations was performed to identify trends relating to potential causes. In 45 (57%) reports, parenteral nutrition was identified as the causative agent. Full recovery was documented in 21 (47%) extravasations. Of the total events reported, 83% were reported by pharmacists, 16% by nurses, and <1% by other healthcare practitioners. CONCLUSIONS Results of this study are consistent with those of previous studies involving ADE reporting in children's hospitals. This consistency is due in part to system design and use of unit-based pharmacists as the primary reporters. PMID:22768013

Early outcomes of empiric embolization of tumor-related gastrointestinal hemorrhage in patients with advanced malignancy.

PubMed

Tandberg, Daniel J; Smith, Tony P; Suhocki, Paul V; Pabon-Ramos, Waleska; Nelson, Rendon C; Desai, Svetang; Branch, Stanley; Kim, Charles Y

2012-11-01

To report short-term results of empiric transcatheter embolization for patients with advanced malignancy and gastrointestinal (GI) hemorrhage directly from a tumor invading the GI tract wall. Between 2005 and 2011, 37 mesenteric angiograms were obtained in 26 patients with advanced malignancy (20 men, six women; mean age, 56.2 y) with endoscopically confirmed symptomatic GI hemorrhage from a tumor invading the GI tract wall. Angiographic findings and clinical outcomes were retrospectively evaluated. Clinical success was defined as absence of signs and symptoms of hemorrhage for at least 30 day following embolization. Active extravasation was demonstrated in three cases. Angiographic abnormalities related to a GI tract tumor were identified on 35 of 37 angiograms, including tumor neovascularity (n = 21), tumor enhancement (n = 24), and luminal irregularity (n = 5). In the absence of active extravasation, empiric embolization with particles and/or coils was performed in 25 procedures. Cessation of hemorrhage (ie, clinical success) occurred more frequently when empiric embolization was performed (17 of 25 procedures; 68%) than when embolization was not performed (two of nine; 22%; P = .03). Empiric embolization resulted in clinical success in 10 of 11 patients with acute GI bleeding (91%), compared with seven of 14 patients (50%) with chronic GI bleeding (P = .04). No ischemic complications were encountered. In patients with advanced malignancy, in the absence of active extravasation, empiric transcatheter arterial embolization for treatment of GI hemorrhage from a direct tumor source demonstrated a 68% short-term success rate, without any ischemic complications. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Use of Ultrasound Pulses Combined with Definity for Targeted Blood-Brain Barrier Disruption

NASA Astrophysics Data System (ADS)

McDannold, Nathan; Vykhodtseva, Natalia; Hynynen, Kullervo

2007-05-01

We have developed a method to combine an ultrasound contrast agent (USCA) with low-intensity focused ultrasound pulses combined to produce temporary blood-brain barrier disruption (BBBD), a potential non-invasive means for targeted drug delivery in the brain. All of our previous work used the USCA Optison. The purpose of this work was to test the feasibility of using the USCA Definity for BBBD. Thirty-six non-overlapping locations were sonicated through a craniotomy in experiments in the brains of nine rabbits (4 locations per rabbit; US frequency: 0.69MHz, burst: 10ms, PRF: 1Hz, duration: 20s; pressure amplitude: 0.2-1.5 MPa). Eleven locations were sonicated using Optison at 0.5 MPa. For both agents, the probability for BBBD was estimated to be 50% at 0.4 MPa using probit regression. In histology, small isolated areas of extravasated erythrocytes were observed in some locations. At 0.8 MPa and above, this extravasation was sometimes accompanied by tiny (dimensions of 100 μm or less) regions of damaged brain parenchyma. The magnitude of the BBBD was larger with Optison than with Definity at 0.5 MPa (P=0.04), and more areas with extravasated erythrocytes were observed (P=0.03). We conclude that BBBD is possible using Definity for the dosage of USCA and the acoustic parameters tested in this study. While the probability for BBBD as a function of pressure amplitude and the type of acute tissue effects was similar to findings with Optison, under these experimental conditions, Optison produced a larger effect.

Embolization Therapy for Traumatic Splenic Lacerations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dasgupta, Niloy; Matsumoto, Alan H., E-mail: ahm4d@virginia.edu; Arslan, Bulent

Purpose: This study was designed to evaluate the clinical success, complications, and transfusion requirements based on the location of and agents used for splenic artery embolization in patients with splenic trauma. Methods: A retrospective study was performed of patients with splenic trauma who underwent angiography and embolization from September 2000 to January 2010 at a level I trauma center. Electronic medical records were reviewed for demographics, imaging data, technical aspects of the procedure, and clinical outcomes. Results: Fifty patients were identified (34 men and 16 women), with an average age of 48 (range, 16-80) years. Extravasation was seen on initialmore » angiography in 27 (54%) and was absent in 23 (46%). All 27 patients with extravasation were embolized, and 18 of 23 (78.2%) without extravasation were embolized empirically. Primary clinical success was similar (>75%) across all embolization locations, embolic agents, and grades of laceration treated. Of 45 patients treated, 9 patients (20%) were embolized in the main splenic artery, 34 (75.6%) in the splenic hilum, and 2 (4.4%) were embolized in both locations. Partial splenic infarctions developed in 47.3% treated in the splenic hilum compared with 12.5% treated in the main splenic artery. There were four (8.9%) mortalities: two occurred in patients with multiple critical injuries and two from nonbleeding etiologies. Conclusions: Embolization of traumatic splenic artery injuries is safe and effective, regardless of the location of treatment. Embolization in splenic hilar branches may have a higher incidence of infarction. The grade of laceration and agents used for embolotherapy did not impact the outcomes.« less

Activation states of blood eosinophils in asthma

PubMed Central

Johansson, Mats W.

2014-01-01

Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or “primed”, or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease. PMID:24552191

Vascular extravasation of contrast medium in radiological examinations: University of California San Diego Health System Experience.

PubMed

Niv, Galia; Costa, Matthew; Kicak, Patricia; Richman, Katherine

2014-06-01

Extravasation is a well-recognized complication estimated to be between 0.1% and 0.9% of contrast medium administrations. According to the UC San Diego (UCSD) health system policy, all contrast medium extravasation (CME) reports are reviewed by the department of Risk Management, and the appropriate action is taken. Despite this strategy, a decrease in the incidence of CME could not be demonstrated. The aims of this study were to determine the frequency, management, and outcome of CME in UC San Diego patients and to assess the knowledge regarding CME among radiology technologists based on policy and guidelines. The secondary aim was to assess the manual ability of the radiology technologists in the performance of the procedure. The study has 2 parts; the first was retrospective, including data collection and interpretation of all radiology procedures using intravenous contrast medium injection between January 1, 2010, and September 30, 2011, and the second was prospective, including proactive observations and knowledge questionnaire. There were 83 (0.48%) cases of CME of 17,200 patients, 54 women (0.64%) and 29 men (0.33%), P = 0.005. The patients with CME were older, and their cannula was inserted in other departments than Radiology Department, P < 0.000. There was a gap between the high theoretical knowledge that was found in the knowledge questionnaire and its implementation that was demonstrated in the proactive observation. Our data demonstrate that sex, age, and where the cannula was inserted are predictive factors for CME. We believe that CME could be prevented by proper educational program and establishment of efficient strategy.

Amelioration of Cold Injury-Induced Cortical Brain Edema Formation by Selective Endothelin ETB Receptor Antagonists in Mice

PubMed Central

Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

2014-01-01

Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults. PMID:25000290

The effect of inhaled K+ channel openers on bronchoconstriction and airway microvascular leakage in anaesthetised guinea pigs.

PubMed

Kidney, J C; Lotvall, J O; Lei, Y; Chung, K F; Barnes, P J

1996-01-18

Since orally administered K+ channel openers may have cardiovascular side effects, it is possible that inhaled administration would be preferred for the treatment of asthma. We have investigated whether inhaled levcromakalim and HOE 234 inhibit histamine-induced bronchoconstriction and airway plasma exudation in anaesthetised guinea pigs. We have also investigated whether inhaled HOE 234 inhibits the bronchoconstriction and plasma exudation induced by vagus nerve stimulation, which is due to the release of tachykinins from sensory nerves. Lung resistance was measured by airway resistance (RL) computed from airway and transpulmonary pressures and plasma exudation by measurement of Evans blue dye extravasation. Inhaled levcromakalim (25 mu g/ml) had a short duration of action, being effective against histamine-induced bronchoconstriction 2 min after pretreatment, but not at 10 min. Inhaled HOE 234 (25 mu g/ml) was similarly effective against histamine-induced bronchoconstriction but had a longer duration of action. Inhaled levcromakalim partially attenuated histamine-induced plasma extravasation in small airways, but not in the trachea or main bronchi, whereas inhaled HOE 234 had no effect. HOE 234 protected against non-adrenergic non-cholinergic nerve-induced bronchoconstriction, but had no effect on neurogenic- or substance P-induced plasma extravasation in the airway. Inhaled K+ channel openers protect against induced bronchoconstriction, but provide little or no protection against plasma exudation, possibly because of an increase in airway blood flow. In addition, inhaled HOE 234 had no effect on neurogenic leakage, suggesting that its vagal inhibitory effect on bronchoconstriction was on airway smooth muscle, rather than on release of neuropeptides from sensory nerves.

Thoracic vagal efferent nerve stimulation evokes substance P-induced early airway bronchonstriction and late proinflammatory and oxidative injury in the rat respiratory tract.

PubMed

Li, Ping-Chia; Li, Sheng-Chung; Lin, Yuan-Ju; Liang, Jin-Tung; Chien, Chiang-Ting; Shaw, Chen-Fu

2005-01-01

Electrical stimulation of efferent thoracic vagus nerve (TVN) evoked neurogenic inflammation in respiratory tract of atropine-treated rats by an undefined mechanism. We explored whether efferent TVN stimulation via substance P facilitates neurogenic inflammation via action of nuclear factor-kappaB (NF-kappaB) activation and reactive oxygen species (ROS) production. Our results showed that increased frequency of TVN stimulation concomitantly increased substance P-enhanced hypotension, and bronchoconstriction (increases in smooth muscle electromyographic activity and total pulmonary resistance). The enhanced SP release evoked the appearance of endothelial gap in silver-stained leaky venules, India-ink labeled extravasation, and accumulations of inflammatory cells in the respiratory tract, contributing to trachea plasma extravasation as well as increases in blood O (2)(-) and H(2)O(2) ROS amount. L-732138 (NK(1) receptor antagonist), SR-48968 (NK(2) receptor antagonist), dimethylthiourea (H(2)O(2) scavenger) or catechins (O (2)(-) and H(2)O(2) scavenger) pretreatment reduced efferent TVN stimulation-enhanced hypotension, bronchoconstriction, and plasma extravasation. Increased frequency of TVN stimulation significantly upregulated the expression of nuclear factor-kappaB (NF-kappaB) in nuclear protein and intercellular adhesion molecule-1 (ICAM-1) in total protein of the lower respiratory tract tissue. The upregulation of NF-kappaB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants. In conclusion, TVN efferent stimulation increases substance P release to trigger NF-kappaB mediated ICAM-1 expression and O (2)(-) and H(2)O(2) ROS production in the respiratory tract.

Attenuation of tachykinin-induced airflow obstruction and microvascular leakage in immature airways.

PubMed Central

Tokuyama, K.; Yokoyama, T.; Morikawa, A.; Mochizuki, H.; Kuroume, T.; Barnes, P. J.

1993-01-01

1. To study the effect of maturation on substance P (SP)- and neurokinin A (NKA)-induced airflow obstruction and airway microvascular leakage (MVL), we have measured changes in both lung resistance (RL) and extravasation of Evans blue dye in anaesthetized immature (aged 14 +/- 1 days) and adult guinea-pigs (aged 80 +/- 3 days). 2. RL and its recovery after hyperinflation at 5 min were measured for 6 min after i.v. SP (0.2, 1 and 30 nmol kg-1), NKA (1 and 10 nmol kg-1) or vehicle (0.9% NaCl). After measurement of RL, MVL in trachea, main bronchi and intrapulmonary airways was also examined. 3. The order of potency in inducing airflow obstruction did not change with age (NKA > SP) but immature animals required a larger dose of SP or NKA than adults to cause a significant increase in RL. 4. The order of potency in inducing airway microvascular leakage was SP > NKA in both immature and adult animals. The amount of extravasated dye after SP was significantly less in immature airways, especially in central airways. 5. Phosphoramidon (2.5 mg kg-1), a neutral endopeptidase (NEP) inhibitor, significantly increased RL after 0.2 nmol kg-1 SP only in adult airways. Phosphoramidon enhanced the dye extravasation after 0.2 nmol kg-1 SP in both immature and adult airways with a significantly greater amount of dye in adult animals, suggesting that mechanisms other than changes in NEP activity may be responsible for this age-related difference.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7679033

Visualization and characterization of the acoustic radiation force assisted displacement of particles using an OCT technique (Conference Presentation)

NASA Astrophysics Data System (ADS)

Razani, Marjan; Zam, Azhar; Arezza, Nico J. J.; Wang, Yan J.; Kolios, Michael C.

2016-03-01

In this study, we present a technique to image the enhanced particle displacement generated using an acoustic radiation force (ARF) excitation source. A swept-source OCT (SS-OCT) system with a center wavelength of 1310nm, a bandwidth of ~100nm, and an A-scan rate of 100 kHz (MEMS-VCSEL OCT Thorlabs) was used to detect gold nanoparticle (70nm in diameter) displacement .ARF was applied after the nanoparticles passed through a porous membrane and diffused into a collagen (6% collagen) matrix. B-mode, M-B mode, 3D and Speckle Variance (SV) images were acquired before and after the ARF beam was on. Differential OCT speckle variance images with and without the ARF were used to measure the particle displacement. The images were used to detect the microscopic enhancement of nanoparticle displacement generated by the ARF. Using this OCT imaging technique, the extravasation of particles though a porous membrane and characterization of the enhanced particle displacement in a collagen gel after using an ARF excitation was achieved.

IL-10+ innate-like B cells are part of the skin immune system and require α4β1 integrin to migrate between the peritoneum and inflamed skin1

PubMed Central

Glabman, Raisa A.; Ruthel, Gordon; Hamann, Alf; Debes, Gudrun F.

2016-01-01

The skin is an important barrier organ and frequent target of autoimmunity and allergy. Here we found innate-like B cells that expressed the anti-inflammatory cytokine IL-10 in the skin of humans and mice. Unexpectedly, innate-like B1 and conventional B2 cells showed differential homing capacities with peritoneal B1 cells preferentially migrating into the inflamed skin of mice. Importantly, the skin-homing B1 cells included IL-10 secreting cells. B1 cell homing into the skin was independent of typical skin-homing trafficking receptors and instead required α4β1-integrin. Moreover, B1 cells constitutively expressed activated β1 integrin and relocated from the peritoneum to the inflamed skin and intestine upon innate stimulation, indicating an inherent propensity to extravasate into inflamed and barrier sites. We conclude that innate-like B cells migrate from central reservoirs into skin, adding an important cell type with regulatory and protective functions to the skin immune system. PMID:26851219

The Risks of Scuba Diving: A Focus on Decompression Illness

PubMed Central

2014-01-01

Decompression Illness includes both Decompression Sickness (DCS) and Pulmonary Overinflation Syndrome (POIS), subsets of diving-related injury related to scuba diving. DCS is a condition in which gas bubbles that form while diving do not have adequate time to be resorbed or “off-gassed,” resulting in entrapment in specific regions of the body. POIS is due to an overly rapid ascent to the surface resulting in the rupture of alveoli and subsequent extravasation of air bubbles into tissue planes or even the cerebral circulation. Divers must always be cognizant of dive time and depth, and be trained in the management of decompression. A slow and controlled ascent, plus proper control of buoyancy can reduce the dangerous consequences of pulmonary barotrauma. The incidence of adverse effects can be diminished with safe practices, allowing for the full enjoyment of this adventurous aquatic sport. PMID:25478296

Gamma-Terpinene Modulates Acute Inflammatory Response in Mice.

PubMed

Ramalho, Theresa Raquel de Oliveira; Oliveira, Maria Talita Pacheco de; Lima, Ana Luisa de Araujo; Bezerra-Santos, Claudio Roberto; Piuvezam, Marcia Regina

2015-09-01

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1β and tumor necrosis factor-α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. Georg Thieme Verlag KG Stuttgart · New York.

EphrinA4 plays a critical role in α4 and αL mediated survival of human CLL cells during extravasation

PubMed Central

Trinidad, Eva M.; García, Dolores; Soler, Gloria; Ortuño, Francisco J.; Zapata, Agustín G.; Alonso, Luis M.

2016-01-01

A role of endothelial cells in the survival of CLL cells during extravasation is presently unknown. Herein we show that CLL cells but not normal B cells can receive apoptotic signals through physical contact with TNF-α activated endothelium impairing survival in transendothelial migration (TEM) assays. In addition, the CLL cells of patients having lymphadenopathy (LApos) show a survival advantage during TEM that can be linked to increased expression of α4 and αL integrin chains. Within this context, ephrinA4 expressed on the surface of CLL cells sequestrates integrins and inactivates them resulting in reduced adhesion and inhibition of apoptotic/survival signals through them. In agreement, ephrinA4 silencing resulted in increased survival of CLL cells of LApos patients but not LA neg patients. Similarly was observed when a soluble ephrinA4 isoform was added to TEM assays strongly suggesting that accumulation of this isoform in the serum of LApos patients could contribute to CLL cells dissemination and survival in vivo. In supporting, CLL lymphadenopathies showed a preferential accumulation of apoptotic CLL cells around high endothelial venules lacking ephrinA4. Moreover, soluble ephrinA4 isolated from sera of patients increased the number and viability of CLL cells recovered from the lymph nodes of adoptively transferred mice. Finally, we present evidence suggesting that soluble ephrinA4 mediated survival during TEM could enhance a transcellular TEM route of the CLL cells. Together these findings point to an important role of ephrinA4 in the nodal dissemination of CLL cells governing extravasation and survival. PMID:27374180

Vertebral Augmentation with Nitinol Endoprosthesis: Clinical Experience in 40 Patients with 1-Year Follow-up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anselmetti, Giovanni Carlo, E-mail: gc.anselmetti@fastwebnet.it; Manca, Antonio, E-mail: anto.manca@gmail.com; Marcia, Stefano, E-mail: stemarcia@gmail.com

PurposeThis study was designed to assess the clinical outcomes of patients treated by vertebral augmentation with nitinol endoprosthesis (VNE) to treat painful vertebral compression fractures.MethodsForty patients with one or more painful osteoporotic VCF, confirmed by MRI and accompanied by back-pain unresponsive to a minimum 2 months of conservative medical treatment, underwent VNE at 42 levels. Preoperative and postoperative pain measured with Visual Analog Scale (VAS), disability measured by Oswestry Disability Index (ODI), and vertebral height restoration (measured with 2-dimensional reconstruction CT) were compared at last follow-up (average follow-up 15 months). Cement extravasation, subsequent fractures, and implant migration were recorded.ResultsLong-term follow-up was obtainedmore » in 38 of 40 patients. Both VAS and ODI significantly improved from a median of 8.0 (range 5–10) and 66 % (range 44–88 %) to 0.5 (range 0–8) and 6 % (range 6–66 %), respectively, at 1 year (p < 0.0001). Vertebral height measurements comparing time points increased in a statistically significant manner (ANOVA, p < 0.001). Overall cement extravasation rate was 9.5 %. Discal and venous leakage rates were 7.1 and 0 % respectively. No symptomatic extravasations occurred. Five of 38 (13.1 %) patients experienced new spontaneous, osteoporotic fractures. No device change or migration was observed.ConclusionsVNE is a safe and effective procedure that is able to provide long-lasting pain relief and durable vertebral height gain with a low rate of new fractures and cement leakages.« less

Subcutaneous injection of liquid and foamed polidocanol: extravasation is not responsible for skin necrosis during reticular and spider vein sclerotherapy.

PubMed

Schuller-Petrović, S; Pavlović, M D; Neuhold, N; Brunner, F; Wölkart, G

2011-08-01

Cutaneous necrosis is one of the most annoying complications of reticular and spider vein sclerotherapy. The precise incidence of the complication is not known, although various sources reported incidence between 0.2% and 1.2%. Among a few mechanisms proposed to explain it, extravasation of the sclerosant into the perivascular tissue has been cited as the major cause. The aim of the experimental study in rats was to examine the potential of various concentrations and volumes of polidocanol in both liquid and foam forms to cause cutaneous necrosis after superficial subcutaneous injection. Twenty-four female Sprague Dawley rats were injected subcutaneously different concentrations (0.5%, 1%, 2% and 3%) of polidocanol as well as different preparations of polidocanol (liquid vs. foam) and volumes (0.1-0.5 mL). The animals were sacrificed 10 days after injections and biopsy specimens were obtained. Cutaneous necrosis was not seen at volumes <0.5 mL regardless of the concentration or form of polidocanol injected. Foam preparation was shown to be less potent in inducing necrosis with a minimal strength being 2% in comparison with the liquid form where 1% was sufficient to produce overt cutaneous necrosis. This experimental study shows that extravasation of polidocal in usual circumstances of sclerotherapy of spider and reticular veins cannot be a significant cause of cutaneous necrosis rarely observed in this setting. It is particularly true for the foamed polidocanol where 1% strength seems safe if injected extravascularly in volumes up to 0.5 mL. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

PubMed

Kleiter, Miriam M; Yu, Daohai; Mohammadian, Lenore A; Niehaus, Nelsen; Spasojevic, Ivan; Sanders, Linda; Viglianti, Benjamin L; Yarmolenko, Pavel S; Hauck, Marlene; Petry, Neil A; Wong, Terence Z; Dewhirst, Mark W; Thrall, Donald E

2006-11-15

A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)-labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

Mechanical disruption of the blood-brain barrier following experimental concussion.

PubMed

Johnson, Victoria E; Weber, Maura T; Xiao, Rui; Cullen, D Kacy; Meaney, David F; Stewart, William; Smith, Douglas H

2018-05-01

Although concussion is now recognized as a major health issue, its non-lethal nature has limited characterization of the underlying pathophysiology. In particular, potential neuropathological changes have typically been inferred from non-invasive techniques or post-mortem examinations of severe traumatic brain injury (TBI). Here, we used a swine model of head rotational acceleration based on human concussion to examine blood-brain barrier (BBB) integrity after injury in association with diffuse axonal injury and glial responses. We then determined the potential clinical relevance of the swine concussion findings through comparisons with pathological changes in human severe TBI, where post-mortem examinations are possible. At 6-72 h post-injury in swine, we observed multifocal disruption of the BBB, demonstrated by extravasation of serum proteins, fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal pathology. BBB disruption was observed in a stereotyped distribution consistent with biomechanical insult. Specifically, extravasated serum proteins were frequently observed at interfaces between regions of tissue with differing material properties, including the gray-white boundary, periventricular and subpial regions. In addition, there was substantial overlap of BBB disruption with regions of axonal pathology in the white matter. Acute perivascular cellular uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP-positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive). Parallel examination of human severe TBI revealed similar patterns of serum extravasation and glial uptake of serum proteins, but to a much greater extent than in the swine model, attributed to the higher injury severity. These data suggest that BBB disruption represents a new and important pathological feature of concussion.

The matricellular protein CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and suppressing anoikis.

PubMed

Huang, Yu-Ting; Lan, Qiang; Lorusso, Girieca; Duffey, Nathalie; Rüegg, Curzio

2017-02-07

Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression. Here, we investigated the role of CYR61 in breast cancer lung metastasis using the triple negative human breast cancer cell lines MDA-MB-231 and SUM159. Silencing of CYR61 significantly decreased lung metastasis from tumors orthotopically implanted in pre-irradiated or naive mammary tissue and upon tail vein injection. Constitutive CYR61 silencing impaired cancer cell extravasation to the lung during the first 24 hours after tail vein injection. In contrast, CYR61 inducible silencing starting 24 hours after cancer cell injection had no impact on lung metastasis formation. In vitro experiments revealed that CYR61 silencing decreased cancer cell transendothelial migration and motility, reduced CYR61 levels present at the cell surface and sensitized cancer cells to anoikis. Furthermore, we demonstrate that CYR61-dependent cell survival under non-adhesive conditions relied, at least partially, on β1 integrin ligation and AMPKα signaling while it was independent of AKT, FAK and ERK1/2 activation. Our data provide the first evidence that CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and protecting from anoikis during initial seeding to the lung. The uncovered CYR61-β1 integrin-AMPKα axis may serve as a potential therapeutic target to prevent breast cancer metastasis to the lung.

Post-junctional facilitation of substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I

PubMed Central

Wei, Tzuping; Li, Wen-wu; Guo, Tian-Zhi; Zhao, Rong; Wang, Liping; Clark, David J; Oaklander, Ann Louise; Schmelz, Martin; Kingery, Wade S.

2009-01-01

Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. Hindpaw skin extravasation responses and SP receptor (NK1), CGRP receptor (calcitonin receptor-like receptor, CRLR) and neutral endopeptidase (NEP) protein levels were also determined. Gene expression levels of these peptides, receptors, and peptidase were examined in the DRG and skin. Spontaneous and intravenous SP-evoked extravasation responses were increased ipsilateral, but not contralateral to the fracture. Fracture increased SP and CGRP gene expression in the ipsilateral L4,L5 DRG and neuropeptide protein levels in the sciatic nerve and in serum, but had no effect on electrically-evoked SP and CGRP release. NK1 receptor expression was increased in the ipsilateral hindpaw skin keratinocytes and endothelial cells after injury, but CRLR and NEP expression were unchanged. Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb. PMID:19464118

Post-junctional facilitation of Substance P signaling in a tibia fracture rat model of complex regional pain syndrome type I.

PubMed

Wei, Tzuping; Li, Wen-Wu; Guo, Tian-Zhi; Zhao, Rong; Wang, Liping; Clark, David J; Oaklander, Anne Louise; Schmelz, Martin; Kingery, Wade S

2009-08-01

Tibia fracture in rats evokes nociceptive, vascular, and bone changes resembling complex regional pain syndrome (CRPS). Substance P (SP) signaling contributes to the hindpaw warmth, increased vascular permeability, and edema observed in this model, suggesting that neurogenic inflammatory responses could be enhanced after fracture. Four weeks after tibia fracture we measured SP and calcitonin gene-related peptide (CGRP) protein levels in the sciatic nerve and serum. Hindpaw skin extravasation responses and SP receptor (NK1), CGRP receptor (calcitonin receptor-like receptor, CRLR) and neutral endopeptidase (NEP) protein levels were also determined. Gene expression levels of these peptides, receptors, and peptidase were examined in the DRG and skin. Spontaneous and intravenous SP-evoked extravasation responses were increased ipsilateral, but not contralateral to the fracture. Fracture increased SP and CGRP gene expression in the ipsilateral L4,L5 DRG and neuropeptide protein levels in the sciatic nerve and in serum, but had no effect on electrically evoked SP and CGRP release. NK1 receptor expression was increased in the ipsilateral hindpaw skin keratinocytes and endothelial cells after injury, but CRLR and NEP expression were unchanged. Fracture also increased epidermal thickness, but had no effect on epidermal skin neurite counts. These results demonstrate that spontaneous and intravenous SP-evoked extravasation responses are enhanced in the ipsilateral hindlimb after fracture and that fracture chronically increases the expression of endothelial and keratinocyte NK1 receptors in the injured limb. We postulate that SP activation of these up-regulated NK1 receptors results in skin warmth, protein leakage, edema, and keratinocyte proliferation in the injured limb.