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Sample records for artery urokinase infusion

  1. Transradial Approach for Transcatheter Selective Superior Mesenteric Artery Urokinase Infusion Therapy in Patients with Acute Extensive Portal and Superior Mesenteric Vein Thrombosis

    SciTech Connect

    Wang Maoqiang Guo Liping; Lin Hanying; Liu Fengyong; Duan Feng; Wang Zhijun

    2010-02-15

    The purpose of this investigation was to assess the feasibility and effectiveness of transradial approach for transcatheter superior mesenteric artery (SMA) urokinase infusion therapy in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were treated by transcatheter selective SMA urokinase infusion therapy by way of the radial artery. The mean age of the patients was 39.5 years. Through the radial sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of urokinase was performed for 5-11 days (7.1 {+-} 2.5 days). Adequate anticoagulation was given during treatment, throughout hospitalization, and after discharge. Technical success was achieved in all 16 patients. Substantial clinical improvement was seen in these 16 patients after the procedure. Minor complications at the radial puncture site were observed in 5 patients, but trans-SMA infusion therapy was not interrupted. Follow-up computed tomography scan before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The 16 patients were discharged 9-19 days (12 {+-} 6.0 days) after admission. Mean duration of follow-up after hospital discharge was 44 {+-} 18.5 months, and no recurrent episodes of PV-SMV thrombosis developed during that time period. Transradial approach for transcatheter selective SMA urokinase infusion therapy in addition to anticoagulation is a safe and effective therapy for the management of patients with acute extensive PV-SMV thrombosis.

  2. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    SciTech Connect

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-03-15

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate.

  3. Tirofiban combined with urokinase selective intra-arterial thrombolysis for the treatment of middle cerebral artery occlusion

    PubMed Central

    FENG, LEI; LIU, JUN; LIU, YUNZHEN; CHEN, JIAN; SU, CHUNHAI; LV, CHUANFENG; WEI, YUZHEN

    2016-01-01

    The aims of the present study were to establish a model of embolic stroke in rabbits and to evaluate the efficacy and safety of intra-arterially administered tirofiban combined with urokinase thrombolysis. The middle cerebral artery occlusion model (MCAO) of embolic stroke was established in New Zealand rabbits via an autologous clot. The model rabbits were allocated at random into four groups: Tirofiban group (T group), urokinase group (UK group), tirofiban and urokinase group (T + UK group) and the control group (C group). The recanalization rate, relative-apparent diffusion coefficient (rADC) and neurological function deficit score (NFDS) values were compared among the four groups. The recanalization rate, rADC and NFDS values were improved in the T + UK group compared with the other groups. In summary, the intra-arterial administration of tirofiban combined with urokinase thrombolysis was a more effective intervention in an MCAO model compared with intra-arterial urokinase alone, and may promote reperfusion and reduce infarct volume. PMID:26998029

  4. Mixing during intravertebral arterial infusions in an in vitro model.

    PubMed

    Lutz, Robert J; Warren, Kathy; Balis, Frank; Patronas, Nicholas; Dedrick, Robert L

    2002-06-01

    Regional delivery of drugs can offer a pharmacokinetic advantage in the treatment of localized tumors. One method of regional delivery is by intra-arterial infusion into the basilar/vertebral artery network that provides local access to infratentorial tumors, which are frequent locations of childhood brain cancers. Proper delivery of drug by infused solutions requires adequate mixing of the infusate at the site of infusion within the artery lumen. Our mixing studies with an in vitro model of the vertebral artery network indicate that streaming of drug solution is likely to occur at low, steady infusion rates of 2 ml/min. Streaming leads to maldistribution of drug to distal perfused brain regions and may result in toxic levels in some regions while concurrently yielding subtherapeutic levels in adjacent regions. According to our model findings, distribution to both brain hemispheres is not likely following infusion into a single vertebral artery even if the infusate is well-mixed at the infusion site. This outcome results from the unique fluid flow properties of two converging channels, which are represented by the left and right vertebral branches converging into the basilar. Fluid in the model remains stratified on the side of the basilar artery served by the infused vertebral artery. Careful thought and planning of the methods of intravertebral drug infusions for treating posterior fossa tumors are required to assure proper distribution of the drug to the desired tissue regions. Improper delivery may be responsible for some noted toxicities or for failure of the treatments. PMID:12164691

  5. Urokinase infusion of chronically occluded femoropopliteal Gortex bypass grafts via the popliteal approach.

    PubMed

    Dorros, G; Hall, P; Iyer, S S

    1991-11-01

    Thrombolysis of two occluded above-knee femoropopliteal Gortex bypass grafts utilizing the popliteal approach for catheter placement was successfully performed without complication. In both cases, the proximal anastomoses of the graft could not be identified. A percutaneous popliteal approach was used for catheter placement and delivery of urokinase. Angioplasty was performed on the unveiled stenoses that, presumptively, led to graft closure. Selective thrombolysis via catheter placed from popliteal approach is a new technique for recanalization of occluded femoropopliteal bypass grafts and warrants further investigation. PMID:1764742

  6. Hepatobiliary scintigraphy in patients receiving hepatic artery infusion chemotherapy

    SciTech Connect

    Housholder, D.F.; Hynes, H.E.; Dakhil, S.R.; Marymont, J.V.

    1985-05-01

    Hepatic artery infusion chemotherapy is used in the treatment of certain selected hepatic tumors, especially metastatic adenocarcinoma of the colon. Chemical cholecystitis has been recognized recently as a complication of hepatic artery infusion chemotherapy. The authors performed hepatobiliary scans on ten patients receiving hepatic artery infusion chemotherapy. All ten patients had abnormal hepatobiliary scintigraphy. They present case reports of three patients with abnormal hepatobiliary scans who have required cholecystectomy for symptoms of chemical cholecystitis to illustrate the clinical, scintigraphic, and pathologic findings in these patients.

  7. Current Status of Hepatic Arterial Infusion Chemotherapy

    PubMed Central

    Obi, Shuntaro; Sato, Shinpei; Kawai, Toshihiro

    2015-01-01

    Background Hepatic arterial infusion chemotherapy (HAIC) is frequently used to treat advanced hepatocellular carcinoma (HCC) in Asian countries. However, there is a lack of evidence supporting the use of HAIC. Summary Many studies report high response rates in patients with advanced HCC receiving HAIC, and clinical responses translate to survival benefits. Therefore, prediction of an antitumor response is important in selecting appropriate treatments. There are no proven post-sorafenib therapeutic measures or procedures for HCC patients with poor liver function, and HAIC is one of the few options for patients in these situations. Despite studies showing its effectiveness, the use of HAIC for treatment of advanced HCC is unclear because convincing data from large-scale randomized clinical trials are lacking. For HAIC to become a standard treatment for HCC, such trials must establish its efficacy compared with other HCC therapies; prediction of antitumor response in HAIC may aid trial design, and a multi-center, open-labelled, randomized clinical trial of HAIC in advanced HCC is currently in progress. Optimization of HCC treatment protocols and regimens is also required. Key message We think that both HAIC and sorafenib are effective treatments for advanced HCC, and this review presents evidence supporting this contention. PMID:26674592

  8. Cerebral arterial air embolism in a child after intraosseous infusion

    PubMed Central

    Knoester, H.; Maes, A.; van der Wal, A. C.; Kubat, B.

    2008-01-01

    Cerebral arterial air embolism (CAAE) has been reported as a rare complication of medical intervention. There has been one reported case of CAAE after the use of an intraosseous infusion (IO) system. We report on a case of CAAE after tibial IO infusion in a 7-month-old girl during resuscitation. PMID:18247071

  9. Pulmonary Arterial Hypertension: A Focus on Infused Prostacyclins.

    PubMed

    Stewart, Traci

    2016-01-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed. PMID:27598071

  10. [Effect of intravenous lidocaine infusion on arterial baroreflex].

    PubMed

    Yoneda, I

    1993-05-01

    The purpose of the first study was to identify the relationship between reflex sympathetic nerve activity and plasma concentration of lidocaine. Lidocaine was infused in 4 different doses: 2 mg.kg-1 bolus + 100 micrograms.kg-1 x min-1, 3 mg.kg-1 bolus + 200 micrograms.kg-1 x min-1, 6 mg.kg-1 bolus + 400 micrograms.kg-1 x min-1 and 12 mg.kg-1 bolus + 800 micrograms.kg-1 x min-1. Baroreflex depressor and pressor tests using sodium nitroprusside (5-10 micrograms.kg-1) and phenylephrine (2-4 micrograms.kg-1) were performed before and at 10 min after the start of lidocaine infusion. Plasma lidocaine concentrations determined by HPLC revealed that its steady-state levels were maintained during the baroreflex tests. Baroreflex sensitivity was preserved at clinical concentrations of lidocaine (< 5 micrograms.ml-1). However, baroreflex was significantly attenuated when plasma lidocaine concentrations were above seizure levels (> 10 micrograms.ml-1). This result indicates that hemodynamic derangement observed in the lidocaine-induced CNS toxicity is, at least in part, due to the attenuated arterial baroreflex. In the second study, the author evaluated the effect of respiratory acidosis and alkalosis on the baroreflex with or without lidocaine infusion (2 mg.kg-1 + 100 micrograms.kg-1 x min-1). Respiratory acidosis (PaCO2: 65.6 +/- 3.4) enhanced the baroreflex significantly, but lidocaine infusion abolished this acidosis-induced enhancement. The author concludes that hypercarbia should be avoided in patients receiving intravenous lidocaine infusion. PMID:8515540

  11. Robotic-assisted placement of a hepatic artery infusion catheter for regional chemotherapy.

    PubMed

    Hellan, Minia; Pigazzi, Alessio

    2008-02-01

    Hepatic arterial infusion chemotherapy can be of value to patients with metastatic liver disease from colorectal cancer. Arterial infusion therapy requires surgical placement of a catheter into the gastroduodenal artery connected to a subcutaneous infusion pump or port, a procedure involving major abdominal surgery. Placement of chemotherapy infusion catheters by conventional laparoscopic techniques has been described, but is a technically challenging procedure. The purpose of this report is to introduce a new, minimally invasive approach for hepatic artery catheter placement using the DaVinci robotic system with the potential to minimize surgical trauma, pain, and hospital stay, and to render this minimal access procedure more feasible and widely applicable. PMID:17704873

  12. Hepatobiliary scintigraphy in patients receiving hepatic artery infusion chemotherapy

    SciTech Connect

    Housholder, D.F.; Hynes, H.E.; Dakhil, S.R.; Marymont, J.H. Jr.

    1984-01-01

    Two patients receiving hepatic artery infusion chemotherapy (HAIC) required cholecystectomy for both acute and chronic cholecystitis with cholelithiasis suggesting chemical cholecystitis. To evaluate the incidence of gall bladder dysfunction in patients receiving HAIC, the authors performed hepatobiliary scintigraphy using Tc-99m DISIDA or PIPIDA on eight patients receiving HAIC through an indwelling hepatic artery catheter and Infusaid (trademark) pump. In 7 of 8 patients, there was non-visualization of the gall bladder throughout the hepatobiliary study. In the eighth patient, the gall bladder visualized at 2 hr. One patient with non-visualization of the gall bladder at 4 hr developed acute symptoms requiring cholecystectomy which showed acute and chronic cholecystitis with cholethiasis. There was prominent sclerosis which was thought to be due to chemical cholecystitis as well as cholelithiasis. In all 10 patients, no evidence of cholecystitis had been observed during the surgical placement of the hepatic artery catheter and Infusaid pump. The hepatobiliary scintigraphic finding of gall bladder dysfunction in all eight patients studied is most likely due to chemical cholecystitis from HAIC. This series suggests that chemical cholecystitis is common during HAIC and can be identified by hepatobiliary scintigraphy. The authors consider elective cholecystectomy during the operative placement of the hepatic artery catheter and Infusaid pump.

  13. Mixing in the human carotid artery during carotid drug infusion studied with PET.

    PubMed

    Junck, L; Koeppe, R A; Greenberg, H S

    1989-10-01

    The safety and efficacy of drug infusion into the carotid artery require adequate mixing of the infused solution with carotid blood. Using positron emission tomography (PET), we studied the mixing of solutions infused into the human carotid artery in seven patients by analyzing the distribution of [15O]H2O infused into the carotid artery and by vein. At four infusion rates ranging from 0.5 to 10 ml/min, the variability in distribution averaged 16.5-17.8% among the pixels in a large volume of interest, without dependence on the infusion rate. The overall correlation between [15O]H2O influx with arterial infusion and [15O]H2O influx with venous injection was 0.78-0.82 at the four infusion rates, with no trend toward higher correlations at the faster infusion rates. The distribution into the anterior, middle, and posterior cerebral artery territories differed from distribution throughout the entire carotid territory by an average of 6.2-9.6% at the four infusion rates, with no trend toward smaller differences at the faster infusion rates. Infusions performed into a vinyl tube simulating the carotid artery indicated that at 0.5 ml/min, the velocity of fluid exiting the catheter makes no apparent contribution to mixing. We conclude that with infusions at the carotid bifurcation, mixing in the human carotid artery is complete or nearly complete over a wide range of infusion rates. The mixing appears to result from the patterns of blood flow within the artery, and not from jet effects at the catheter tip. PMID:2789230

  14. Hemodynamic responses of the equine digit to intravenous and digital arterial infusion of dopamine.

    PubMed

    Hunt, R J; Moore, J N; Allen, D

    1990-04-01

    In 6 adult horses anesthetized with pentobarbital, the hemodynamic responses of the equine digit to infusion of dopamine were evaluated by use of an isolated extra corporeal pump perfused digital preparation. Digital blood flow was maintained at a constant rate that was independent of systemic hemodynamic changes. Three sequential experiments were performed on each horse. In the first experiment (n = 6), dopamine was infused IV at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. For the second experiment (n = 5), dopamine (400 micrograms/ml) was infused into the digital artery at the rates of 0.07, 0.7, and 1.2 ml/min. The third experiment (n = 5) consisted of a 5-minute intra-arterial infusion of phentolamine followed by the intra-arterial infusion of dopamine while continuing the infusion of phentolamine. Digital venous, arterial, and capillary pressures, total digital vascular resistance, and precapillary to postcapillary resistance ratios were determined in each experiment. Systemic infusion of dopamine did not induce changes in the hemodynamics of the digital vasculature. Digital arterial infusion of dopamine alone resulted in a dose-dependent increase in arterial pressure, total digital vascular resistance, and an increase in the precapillary to postcapillary resistance ratio. Phentolamine attenuated the vasoconstrictive response elicited by intra-arterial infusion of dopamine. PMID:2327616

  15. Hepatic metastasis from esophageal cancer treated by surgical resection and hepatic arterial infusion chemotherapy.

    PubMed

    Hanazaki, K; Kuroda, T; Wakabayashi, M; Sodeyama, H; Yokoyama, S; Kusama, J

    1998-01-01

    We herein describe a successful surgical resection of esophageal cancer with syncronous liver metastasis and report the first case of a partial response to hepatic arterial infusion chemotherapy for recurrence of esophageal hepatic metastasis after hepatectomy. Hepatectomy and subsequent hepatic arterial infusion chemotherapy with cisplatin and 5-fluorouracil is thus recommended as an effective treatment for liver metastasis from esophageal cancer. PMID:9496513

  16. Sclerosing cholangitis after continuous hepatic artery infusion of FUDR.

    PubMed Central

    Kemeny, M M; Battifora, H; Blayney, D W; Cecchi, G; Goldberg, D A; Leong, L A; Margolin, K A; Terz, J J

    1985-01-01

    Eight of 46 (17.4%) patients treated in our trial of continuous hepatic artery infusion (CHAI) of fluorodeoxyuridine (FUDR) by Infusaid pump developed biliary strictures. The lesions were clinically, radiographically, and pathologically identical to the idiopathic sclerosing cholangitis frequently seen in association with inflammatory bowel disease. Treatment included immediate cessation of intraarterial FUDR, and surgical or percutaneous drainage of the biliary tree if it was dilated. Two of the eight patients died of the complication. Three patients stabilized after biliary system drainage, and two patients improved on observation only. The pathogenesis of this complication is not understood. This report details the clinical and pathological features of this entity. Images FIG. 1. FIG. 2. FIG. 3. FIG. 4. FIG. 5. FIG. 6. FIG. 7. PMID:3160313

  17. Safety of Chemotherapeutic Infusion or Chemoembolization for Hepatocellular Carcinoma Supplied Exclusively by the Cystic Artery

    SciTech Connect

    Kang, Beomsik Kim, Hyo-Cheol Chung, Jin Wook Hur, Saebeom Joo, Seung-Moon Jae, Hwan Jun Park, Jae Hyung

    2013-10-15

    Purpose: This study was designed to evaluate the safety of chemotherapeutic infusion or chemoembolization by way of the cystic artery in patients with hepatocellular carcinoma (HCC) supplied exclusively by the cystic artery. Methods: Between Jan 2002 and Dec 2011, we performed chemotherapeutic infusion or chemoembolization using iodized oil for the treatment of 27 patients with HCC supplied exclusively by the cystic artery. Computed tomography (CT) scans, digital subtraction angiograms, and medical records were retrospectively reviewed by consensus. Results: The cystic artery originated from the main right hepatic artery in 24 (89 %) patients, from the right anterior hepatic artery in 2 (7 %) patients, and from the left hepatic artery in 1 (4 %) patient. Selective catheterization of the cystic artery was achieved in all patients. Superselection of tumor-feeding vessels from the cystic artery was achieved in 7 patients (26 %). Chemotherapeutic infusion was performed in 18 patients (67 %), and chemoembolization was performed in 9 patients (33 %). There were no major complications and only 2 minor complications, including vasovagal syncope and nausea with vomiting. Individual tumor response supplied exclusively by the cystic artery at the follow-up enhanced CT scan were complete response (n = 16), partial response (n = 3), and stable disease (n = 8). Conclusion: HCC supplied exclusively by the cystic artery can be safely treated without severe complications by chemotherapeutic infusion or chemoembolization using iodized oil through the cystic artery.

  18. Transcatheter Arterial Infusion of Autologous CD133+ Cells for Diabetic Peripheral Artery Disease

    PubMed Central

    Zhang, Xiaoping; Lian, Weishuai; Lou, Wensheng; Han, Shilong; Lu, Chenhui; Zuo, Keqiang; Su, Haobo; Xu, Jichong; Cao, Chuanwu; Tang, Tao; Jia, Zhongzhi; Jin, Tao; Uzan, Georges; Gu, Jianping; Li, Maoquan

    2016-01-01

    Microvascular lesion in diabetic peripheral arterial disease (PAD) still cannot be resolved by current surgical and interventional technique. Endothelial cells have the therapeutic potential to cure microvascular lesion. To evaluate the efficacy and immune-regulatory impact of intra-arterial infusion of autologous CD133+ cells, we recruited 53 patients with diabetic PAD (27 of CD133+ group and 26 of control group). CD133+ cells enriched from patients' PB-MNCs were reinfused intra-arterially. The ulcer healing followed up till 18 months was 100% (3/3) in CD133+ group and 60% (3/5) in control group. The amputation rate was 0 (0/27) in CD133+ group and 11.54% (3/26) in control group. Compared with the control group, TcPO2 and ABI showed obvious improvement at 18 months and significant increasing VEGF and decreasing IL-6 level in the CD133+ group within 4 weeks. A reducing trend of proangiogenesis and anti-inflammatory regulation function at 4 weeks after the cells infusion was also found. These results indicated that autologous CD133+ cell treatment can effectively improve the perfusion of morbid limb and exert proangiogenesis and anti-inflammatory immune-regulatory impacts by paracrine on tissue microenvironment. The CD133+ progenitor cell therapy may be repeated at a fixed interval according to cell life span and immune-regulatory function. PMID:26981134

  19. Vascular Access System for Continuous Arterial Infusion of a Protease Inhibitor in Acute Necrotizing Pancreatitis

    SciTech Connect

    Ganaha, Fumikiyo; Yamada, Tetsuhisa; Yorozu, Naoya; Ujita, Masuo; Irie, Takeo; Fukuda, Yasushi; Fukuda, Kunihiko; Tada, Shimpei

    1999-09-15

    We used a vascular access system (VAS) for continuous arterial infusion (CAI) of a protease inhibitor in two patients with acute necrotizing pancreatitis. The infusion catheter was placed into the dorsal pancreatic artery in the first patient and into the gastroduodenal artery in the second, via a femoral artery approach. An implantable port was then connected to the catheter and was secured in a subcutaneous pocket prepared in the right lower abdomen. No complications related to the VAS were encountered. This system provided safe and uncontaminated vascular access for successful CAI for acute pancreatitis.

  20. Dependence of intestinal glucose absorption on sodium, studied with a new arterial infusion technique

    PubMed Central

    Fisher, R. B.; Gardner, M. L. G.

    1974-01-01

    1. A new preparation of isolated rat jejunum plus ileum (ca. 100 cm) is described in which a saline infusate is pumped into the superior mesenteric artery, the superior mesenteric vein having been ligated. 2. The arterial infusate washes out the tissue spaces: the lumen is perfused in a single pass with a segmented flow as by Fisher & Gardner (1974). 3. At an arterial infusion rate of 3 ml./min, steady states are set up in the tissue fluid within 10-15 min: the compositions of the fluids bathing both sides of the mucosa can therefore be controlled. 4. The rate of glucose absorption from the lumen falls only gradually when the luminal sodium is replaced by choline abruptly while the tissue fluid sodium is maintained at 144 m-equiv/l. by arterial infusion. 5. The rate of glucose absorption from the lumen is unaffected by replacement of sodium in the arterial infusate by choline. 6. Ouabain (10-4 M) in an arterial infusate containing sodium 144 m-equiv/l. causes inhibition of glucose and water absorption from the lumen. There is no effect of ouabain when the arterial infusate contains sodium, 0 or 72 m-equiv/l. 7. Arterial ouabain does not reverse the effects of depletion of luminal sodium. Simultaneous removal of luminal sodium and application of arterial ouabain causes faster inhibition of glucose absorption than does either treatment alone. 8. Glucose absorption is more likely to depend on rate of efflux of sodium from mucosal cell to tissue fluid than on a sodium gradient at the brush border or on intracellular sodium concentration. PMID:4422318

  1. Hepatic artery infusion and chemoembolization in the management of liver metastases.

    PubMed

    Wallace, S; Carrasco, C H; Charnsangavej, C; Richli, W R; Wright, K; Gianturco, C

    1990-01-01

    Hepatic metastases rather than the primary neoplasm usually dictate the course of the disease and patient's survival. For unresectable disease, intraarterial infusion of chemotherapy, embolization, and chemoembolization are viable alternatives. Intraarterial therapy for hepatic metastases is based on the dual blood supply of the normal liver (portal vein, 75%, and hepatic artery, 25%) and that of the tumors (hepatic artery, 90%). Intraarterial infusion delivers a higher concentration of chemotherapy, whereas chemoembolization adds ischemia and increased contact time with the tumor. Selective vascular occlusion for infusion, redistribution of the blood supply and pulsatile flow enhance the delivery of therapeutic agents to the liver. PMID:2121343

  2. Increased skin lymph protein clearance after a 6-h arterial bradykinin infusion.

    PubMed

    Mullins, R J; Hudgens, R W

    1987-12-01

    When bradykinin (0.15-0.28 micrograms.kg-1.min-1) was infused into both femoral arteries of 11 anesthetized dogs, skin lymph flows increased by 25-371% within 2 h, and mean lymph protein concentrations increased by one-third. To determine whether, in addition to the initial increase in permeability, a 6.5- to 10-h bradykinin infusion caused a sustained effect, the bradykinin infusion into one hindpaw was stopped after 2 h (2HR), whereas the contralateral hindpaw was infused continuously (CONT). Two hours after the bradykinin infusion was stopped, Ringer lactate equal to 10% of the dog's body weight was given intravenously to further increase lymph flow. After Ringer lactate infusion, increase in lymph protein clearance from the CONT hindpaws was greater than that from the 2HR hindpaws (change in clearance from before Ringer lactate infusion to final: 2HR, 6.9 +/- 1.4 to 8.8 +/- 1.1; CONT, 23.4 +/- 2.5 to 40.2 +/- 4.8 microliters/min). In the final lymph samples of the CONT, but not 2HR, hindpaws, the lymph-to-plasma ratio for immunoglobulin G and immunoglobulin M divided by the albumin lymph-to-plasma ratio exceeded the value of these ratios in the base-line samples. An intravenous bolus of Evans blue dye was given less than 2 h before the end of the experiment. The concentrations of dye in the final lymph samples were greater in CONT hindpaws (12.6 +/- 3.7% plasma equivalents) than in the 2HR hindpaws (1.1 +/- 0.5%). A continuous 6.5- to 10-h intra-arterial bradykinin infusion produced a sustained increase of transvascular protein clearance in skin that is consistent with a sustained increase in microvascular membrane permeability. PMID:3425746

  3. Improved myocardial contractility with glucose-insulin-potassium infusion during pacing in coronary artery disease.

    PubMed

    McDaniel, H G; Rogers, W J; Russell, R O; Rackley, C E

    1985-04-01

    The metabolic and mechanical effects of a solution of glucose-insulin-potassium (G-I-K) were investigated in 18 patients who underwent diagnostic cardiac catheterization for coronary artery disease. All patients were paced at a rate of approximately 140 beats/min before and after infusion of G-I-K. Basal and paced left ventricular (LV) end-diastolic pressure, dP/dt, arterial substrate levels and osmolarity were measured in all 18 patients. In 13 patients cardiac index was also measured. In 5 patients arterial-coronary sinus measurements of oxygen, carbon dioxide, glucose, free fatty acids, lactate, alanine, glutamate, glutamine, ammonia and urea were made, in addition to coronary sinus blood flow. G-I-K increased the blood sugar level to approximately 200 mg/dl and raised the serum osmolarity 9 mosmol. Pacing alone raised the cardiac index 4% and pacing with G-I-K increased the cardiac index 6% (p less than 0.05). Pacing before G-I-K augmented dP/dt (21%) and pacing with G-I-K increased it (30%) (p less than 0.01). The metabolic changes noted included a shift in the respiratory quotient from 0.77 to 0.96 with G-I-K infusion (p less than 0.05). During G-I-K infusion the myocardial oxygen consumption at rest increased from 17.1 to 21.8 ml/min (23%, p less than 0.05). Myocardial oxygen consumption during pacing was similar before and after G-I-K infusion. Before G-I-K infusion nitrogen balance was slightly positive; after G-I-K infusion it was negative with regard to the nitrogen-containing compounds measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3885708

  4. Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat

    SciTech Connect

    Saris, S.C.; Wright, D.C.; Oldfield, E.H.; Blasberg, R.G.

    1988-02-01

    Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer--/sup 14/C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions.

  5. Hepatic arterial infusion of mitoxantrone in the treatment of primary hepatocellular carcinoma.

    PubMed

    Shepherd, F A; Evans, W K; Blackstein, M E; Fine, S; Heathcote, J; Langer, B; Taylor, B; Habal, F; Kutas, G; Pritchard, K I

    1987-04-01

    Twenty-three patients (16 male, seven female) with hepatocellular carcinoma (HCC) were treated by hepatic arterial infusion (HAI) of mitoxantrone every 4 weeks. At each treatment, a catheter was inserted percutaneously into the main hepatic artery via the femoral artery under image intensification. Treatment consisted of a 24-hour continuous HAI of mitoxantrone, 6 mg/m2/d X 3 (eight patients) or 10 mg/m2/d X 3 (14 patients) without heparin. Eight patients had only one infusion, nine patients four infusions, five patients three infusions, two patients two infusions, and one patient five infusions. A partial response was seen in six patients, with a median duration of 20 weeks (range, 18 to 38 weeks). Five patients achieved stable disease, with a median duration of 20 weeks (range, 11 to 42 weeks). The median survival of the overall group was 22 weeks. Survivals of responding, stable, and nonresponding patients were 32 weeks, 24 weeks, and 9 weeks, respectively. Complications of catheter placement included asymptomatic dissection of the hepatic artery (one patient), and asymptomatic thrombosis of the hepatic artery (five patients). Three patients experienced mild nausea and vomiting, and six patients had mild to moderate alopecia. Granulocytopenia was frequent at both dose schedules. The granulocyte nadir was greater than 1,000/microL in 34% of evaluable courses, 500 to 1,000/microL in 32%, and less than 500/microL in 34% of courses. Two patients developed neutropenia-associated fever. A platelet nadir below 100,000/microL was seen after only 10% of courses, and only two patients had platelets below 50,000/microL. Seven patients received doxorubicin after progression on mitoxantrone. Four received systemic doxorubicin, 50 mg/m2, and three HAI of doxorubicin, 25 mg/m2, for three days. Two patients achieved partial response (18 weeks and 32 weeks) to HAI doxorubicin. Mitoxantrone has activity in HCC and is well tolerated when administered by HAI. It is not entirely

  6. [A case of intrahepatic cholangiocarcinoma effectively treated by hepatic arterial infusion chemotherapy].

    PubMed

    Nishizawa, Toshihiro; Higuchi, Hajime; Takaishi, Hiromasa; Iizuka, Hideko; Izumiya, Motoko; Yamagishi, Yoshiyuki; Hisamatsu, Tadakazu; Suzuki, Hidekazu; Masaoka, Tatsuhiro; Iwasaki, Eisuke; Nagata, Hiroshi; Hibi, Toshifumi

    2006-11-01

    The patient was a 50-year-old woman who suffered from gastric discomfort. She was first diagnosed as intrahepatic cholangiocarcinoma with hepatic, paraaortic lymphnodal and bone metastasis. Initial systemic chemotherapy using gemcitabine (GEM) and 5-FU failed to control the disease activity. Then she was given GEM and cisplatin (CDDP) combination chemotherapy. The response was assessed as stable disease (SD), but grade 4 leukopenia was seen. Then systemic therapy using GEM, and hepatic arterial infusion therapy with CDDP, l-leucovorin and 5-FU were continued biweekly. Partial response (PR) was achieved six months later, and her disease status was maintained as SD. This hepatic arterial infusion chemotherapy would be safe and feasible as therapy for inoperable intrahepatic cholangiocarcinoma. PMID:17108736

  7. Impact of Multislice CT Angiography on Planning of Radiological Catheter Placement for Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Sone, Miyuki Kato, Kenichi; Hirose, Atsuo; Nakasato, Tatsuhiko; Tomabechi, Makiko; Ehara, Shigeru; Hanari, Takao

    2008-01-15

    The objective of this study was to assess prospectively the role of multislice CT angiography (MSCTA) on planning of radiological catheter placement for hepatic arterial infusion chemotherapy (HAIC). Forty-six patients with malignant liver tumors planned for HAIC were included. In each patient, both MSCTA and intra-arterial digital subtraction angiography (DSA) were performed, except one patient who did not undergo DSA. Comparison of MSCTA and DSA images was performed for the remaining 45 patients. Detectability of anatomical variants of the hepatic artery, course of the celiac trunk, visualization scores of arterial branches and interobserver agreement, presence of arterial stenosis, and technical outcome were evaluated. Anatomical variations of the hepatic artery were detected in 19 of 45 patients (42%) on both modalities. The course of the celiac trunk was different in 12 patients. The visualization scores of celiac arterial branches on MSCTA/DSA were 3.0 {+-} 0/2.9 {+-} 0.2 in the celiac trunk, 3.0 {+-} 0/2.9 {+-} 0.3 in the common hepatic artery, 2.9 {+-} 0.2/2.9 {+-} 0.3 in the proper hepatic artery, 2.9 {+-} 0.3/2.9 {+-} 0.4 in the right hepatic artery, 2.8 {+-} 0.4/2.9 {+-} 0.4 in the left hepatic artery, 2.9 {+-} 0.2/2.9 {+-} 0.3 in the gastroduodenal artery, 2.1 {+-} 0.8/2.2 {+-} 0.9 in the right gastric artery, and 2.7 {+-} 0.8/2.6 {+-} 0.8 in the left gastric artery. No statistically significant differences exist between the two modalities. Interobserver agreement for MSCTA was equivalent to that for DSA. Two patients showed stenosis of the celiac trunk on both modalities. Based on these imaging findings, technical success was accomplished in all patients. In conclusion, MSCTA is accurate in assessing arterial anatomy and abnormalities. MSCTA can provide adequate information for planning of radiological catheter placement for HAIC.

  8. Improved Arterial Blood Oxygenation Following Intravenous Infusion of Cold Supersaturated Dissolved Oxygen Solution

    PubMed Central

    Grady, Daniel J; Gentile, Michael A; Riggs, John H; Cheifetz, Ira M

    2014-01-01

    BACKGROUND One of the primary goals of critical care medicine is to support adequate gas exchange without iatrogenic sequelae. An emerging method of delivering supplemental oxygen is intravenously rather than via the traditional inhalation route. The objective of this study was to evaluate the gas-exchange effects of infusing cold intravenous (IV) fluids containing very high partial pressures of dissolved oxygen (>760 mm Hg) in a porcine model. METHODS Juvenile swines were anesthetized and mechanically ventilated. Each animal received an infusion of cold (13 °C) Ringer’s lactate solution (30 mL/kg/hour), which had been supersaturated with dissolved oxygen gas (39.7 mg/L dissolved oxygen, 992 mm Hg, 30.5 mL/L). Arterial blood gases and physiologic measurements were repeated at 15-minute intervals during a 60-minute IV infusion of the supersaturated dissolved oxygen solution. Each animal served as its own control. RESULTS Five swines (12.9 ± 0.9 kg) were studied. Following the 60-minute infusion, there were significant increases in PaO2 and SaO2 (P < 0.05) and a significant decrease in PaCO2 (P < 0.05), with a corresponding normalization in arterial blood pH. Additionally, there was a significant decrease in core body temperature (P < 0.05) when compared to the baseline preinfusion state. CONCLUSIONS A cold, supersaturated dissolved oxygen solution may be intravenously administered to improve arterial blood oxygenation and ventilation parameters and induce a mild therapeutic hypothermia in a porcine model. PMID:25249764

  9. Gemcitabine-Based Regional Intra-Arterial Infusion Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma

    PubMed Central

    Liu, Xiaoyu; Yang, Xuerong; Zhou, Guofeng; Chen, Yi; Li, Changyu; Wang, Xiaolin

    2016-01-01

    Abstract The present study was carried out to investigate the prognostic factors in patients who received intra-arterial infusion for advanced pancreatic cancer. In addition, the detailed procedure of intra-arterial infusion chemotherapy was described. A total of 354 patients with advanced unresectable pancreatic adenocarcinoma were recruited from January 2012, to April 2015, at Zhongshan Hospital Fudan University, Shanghai, China. Demographic and clinic characteristics of the patients were extracted from electronic medical records. Restricted cubic spline was used to assess the nonliner regression between baseline CA19-9 value and overall survival. Kaplan–Meier analysis and Cox proportional hazard models were used to estimate the association between overall survival and clinical characteristics. Of all 354 included patients, 230 (65%) were male (male/female ratio = 1.8), and 72 (20%) patients were diagnosed with detectable distant metastases. Pretreatment CA19-9 value of patients with metastases was significantly higher as compared to those with locally advanced cancer (median: 922.30 vs 357.00 U/mL, P = 0.0090). Totally 274 patients completed 1 cycle of intra-arterial infusion, whereas 80 patients received 2 or more cycles of the chemotherapy. For all the 354 patients, median OS was 7.0 months (95% CI: 6.0, 8.0 months) with a 6-, 12-, and 18-month survival rate of 0.48, 0.28, and 0.18, respectively. The median OS of patients, who received 1 cycle of intra-arterial infusion therapy, was 6.0 months (95% CI: 5.0, 8.0 months), which was similar to 7.0 months (95% CI: 6.0, 9.0 months) in patients who received 2 or more cycles. Restricted cubic spline revealed the nonline association between baseline CA19-9 and prognosis. The Cox proportional hazard model showed that age, CA19-9 baseline, CA19-9 value, and tumor location were significantly associated with the OS. In conclusion, the gemcitabine-based RIAC presented a potential treatment method for advanced

  10. [Case of gastric perforation after TAI (trancatheter arterial infusion) of SMANCS with special reference to accessory left gastric artery].

    PubMed

    Takeuchi, Nozomu; Shioyama, Yasukazu

    2005-04-01

    In 1993, a 55-year-old-man was diagnosed with chronic active hepatitis (HCV). In January 1999, a solitary hepatocellular carcinoma (HCC) was discovered in his liver S8, and a sub-segmental hepatectomy was performed. In July 1999, multiple recurrences in the liver were noticed, and on August 6, 1999, the first SMANCS-TAE was performed. After that, PEIT was added, and then on July 18, 2000 and November 9, 2000, a second and third SMANCS-TAE were carried out, respectively. This time multiple HCCs in the bilateral lobes were discovered, and the 4 th SMANCS-TAE was undergone on April 12, 2001. On a celiac angiogram, the right hepatic artery was shown to have been obliterated by the last TAE. In addition, accessory left gastric artery (accessory LGA) originating in the left hepatic artery (LHA) proximal to the umbilical point (UP) could be seen. So we advanced a microcatheter to the LHA distal to the accessory LGA and injected SMANCS (0.8 mg) into the left hepatic artery. On April 24, he was admitted to hospital by ambulance due to severe upper abdominal pain. The muscular defense was noticed, and an air pocket under the diaphragm was indicated on an X-ray. An emergency total gastrectomy and R-Y re-construction were performed under the diagnosis of gastric perforation. A hole of approximately 10 cm in diameter was found in the anterior wall between the cardia and the upper body, and the accessory left gastric artery (LGA) was obliterated. The principal known side effects of SMANCS are fever, nausea and vomiting. However, as far as this writer has investigated, gastric perforation has never been reported. SMANCS presumably can flow into the stomach wall through the accessory LGA, triggering necrosis of the gastric wall due to circulatory damage. Although arterial infusion of SMANCS is an effective treatment, it causes considerable vascular damage, so intensive follow-up treatment is necessary. PMID:15853226

  11. Effects of arterial and venous volume infusion on coronary perfusion pressures during canine CPR.

    PubMed

    Gentile, N T; Martin, G B; Appleton, T J; Moeggenberg, J; Paradis, N A; Nowak, R M

    1991-08-01

    Intraarterial (IA) volume infusion has been reported to be more effective than intravenous (IV) infusion in treating cardiac arrest due to exsanguination. A rapid IA infusion was felt to raise intraaortic pressure and improve coronary perfusion pressure (CPP). The purpose of this study was to determine if IA or IV volume infusion could augment the effect of epinephrine on CPP during CPR in the canine model. Nineteen mongrel dogs with a mean weight of 26.3 +/- 4.2 kg were anesthetized and mechanically ventilated. Thoracic aortic (Ao), right atrial (RA) and pulmonary artery catheters were placed for hemodynamic monitoring. Additional Ao and central venous catheters were placed for volume infusion. Ventricular fibrillation was induced and Thumper CPR was begun after 5 min (t = 5). At t = 10, all dogs received 45 micrograms/kg IV epinephrine. Six animals received epinephrine alone (EPI). Five dogs received EPI plus a 500 cc bolus of normal saline over 3 min intravenously (EPI/IV). Another group (n = 8) received EPI plus the same fluid bolus through the aortic catheter (EPI/IA). Resuscitation was attempted at t = 18 using a standard protocol. There was a significant increase in CPP over baseline in all groups. The changes in CPP from baseline induced by EPI, EPI/IV and EPI/IA were 20.6 +/- 3.7, 22.8 +/- 4.2 and 22.2 +/- 2.4 mmHg, respectively. Volume loading did not augment the effect of therapeutic EPI dosing. By increasing both preload and afterload, volume administration may in fact be detrimental during CPR. PMID:1658894

  12. Selective Ophthalmic Artery Infusion Chemotherapy for Advanced Intraocular Retinoblastoma: CCHMC Early Experience.

    PubMed

    Michaels, Samantha T; Abruzzo, Todd A; Augsburger, James J; Corrêa, Zélia M; Lane, Adam; Geller, James I

    2016-01-01

    Selective ophthalmic artery infusion chemotherapy (SOAIC) is increasingly used to treat retinoblastoma. We report the toxicities and outcome of 19 eyes in 17 patients with retinoblastoma receiving SOAIC treatment between 2008 and 2013. From the 87 treatments, mild local reactions were common. Myelosuppression was more common after triple-agent SOAIC (melphalan, carboplatin, and topotecan) than single-agent melphalan. Ocular salvage was achieved in 11 of 19 eyes and associated with triple-agent therapy. SOAIC is a effective therapy for some retinoblastoma with manageable toxicity; however, systemic toxicity increases with increasing therapeutic intensity of SOAIC. PMID:26583615

  13. Coil herniation following intra-arterial verapamil infusion for the treatment of cerebral vasospasm: Case report and literature review

    PubMed Central

    Chen, Stephanie H; Grandhi, Ramesh; Deibert, Christopher P; Jovin, Tudor G; Gardner, Paul A

    2015-01-01

    Complications associated with intra-arterial infusion of vasodilator agents for the treatment of vasospasm associated with a ruptured cerebral aneurysm are extremely rare. We present the case of a patient who developed left lower extremity monoplegia following intra-arterial infusion of verapamil for treatment of diffuse cerebral vasospasm, 6 days after initially undergoing treatment of a ruptured right A1-2 junction aneurysm. A repeat angiogram following this intra-arterial vasodilator treatment demonstrated a coil loop which had herniated into the right A2 artery. Herein, we describe a previously unreported complication which occurred following intra-arterial pharmacologic vasospasm treatment, review the existing literature, and suggest potential causes and treatment options. PMID:25934655

  14. Complications Encountered with a Transfemorally Placed Port-Catheter System for Hepatic Artery Chemotherapy Infusion

    SciTech Connect

    Kuroiwa, Toshiro; Honda, Hiroshi; Yoshimitsu, Kengo; Irie, Hiroyuki; Aibe, Hitoshi; Tajima, Tsuyoshi; Shinozaki, Kenji; Masuda, Kouji

    2001-03-15

    A port-catheter system was implanted via femoral artery access for hepatic artery chemotherapy infusion. Implantation was attempted in 90 patients and was successful in 88. Blood flow redistribution was performed using embolization coils. In the first ten patients a soft heparin-coated infusion catheter was used. For the following 78 patients we used a stiffer catheter coated with fluorine-acryl-styrene-urethane-silicone (FASUS) copolymer. The catheter was connected to a port implanted subcutaneously below the level of the inguinal ligament. Complications during the procedure and after placement were observed in 7 of 90 patients and 24 of 88 patients, respectively. These included catheter obstruction (11%), dislocation of the catheter tip (10%), drug toxicity (5.7%), and catheter infection (3.4%). In 6 of 10 patients with catheter obstruction, recanalization of the port system was achieved. In 7 of 9 patients with dislocation of the indwelling catheter tip, replacement of the port system was successful. Our complications appear to be comparable with those encountered with the subclavian/brachial approach when the new catheter coating is used. Notable is the avoidance of cerebral infarcts.

  15. Influence of prenatal adrenaline infusion on arterial blood gases after Caesarean delivery in the lamb

    PubMed Central

    Berger, P J; Kyriakides, M A; Smolich, J J; Ramsden, C A; Walker, A M

    2000-01-01

    The efficacy of pulmonary gas exchange immediately after delivery is inversely related to the volume of liquid in the lung at birth, but aspiration of as much liquid as possible from the lung before Caesarean delivery fails to improve postnatal oxygenation (Pa,O2) to the level achieved after spontaneous term delivery. We hypothesised that the differing respiratory benefit of aspiration and vaginal delivery results from the differing volume of lung liquid remaining after aspiration (17 ml (kg body weight)−1) and labour (7 ml kg−1). We addressed this hypothesis by reducing lung liquid volume to an estimated 7 ml kg−1 by infusing adrenaline to seven fetal lambs at 140 days gestation (term is 147 days) before performing Caesarean delivery and obtaining postnatal blood gases for comparison with samples from lambs delivered vaginally. Infusion of adrenaline to fetuses caused a progressive decline in arterial O2 saturation (Sa,O2), pH and base excess, but no change in arterial partial pressure of O2 (Pa,O2) or CO2 (Pa,CO2). After birth, Pa,O2 rapidly rose to the same level in adrenaline-treated and vaginal-delivery groups. A severe acidosis occurred in the adrenaline-treated group and this appeared to be related to a higher Pa,CO2 and a transiently lower Sa,O2 in this group. We conclude that adrenaline infusion can enhance postnatal Pa,O2 levels in the newborn lamb, but this beneficial effect may be outweighed by the severe acidosis that develops after prolonged prenatal adrenaline treatment. PMID:10970438

  16. Continuous Regional Arterial Infusion Therapy for Acute Necrotizing Pancreatitis Due to Mycoplasma pneumoniae Infection in a Child

    SciTech Connect

    Nakagawa, Motoo Ogino, Hiroyuki; Shimohira, Masashi; Hara, Masaki; Shibamoto, Yuta

    2009-05-15

    A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.

  17. Effects of infusion of cardiotomy suction blood during extracorporeal circulation for coronary artery bypass surgery.

    PubMed

    Okies, J E; Goodnight, S H; Litchford, B; Connell, R S; Starr, A

    1977-09-01

    The effects of infusion of cardiotomy suction blood during extracorporeal circulation were evaluated in 15 patients undergoing coronary artery bypass surgery without the use of a left ventricular vent. In Group I all cardiotomy suction blood was discarded. In Groups II and III cardiotomy suction blood was reinfused without and with Dacron wool filtration, respectively. Marked hematologic changes were noted in the pericardial samples which also were reflected in oxygenator samples obtained at the end of bypass. Although postoperative bleeding was significantly greater in patients from Group II as compared to Group I, no differences were seen in total intraoperative and postoperative transfusion requirements. No patient required reoperation for bleeding. Recirculation of larger volumes of cardiotomy suction blood potentially could contribute to bleeding problems in the immediate postoperative period. PMID:142868

  18. Intra-abdominal bleeding during treprostinil infusion in a patient with pulmonary arterial hypertension

    PubMed Central

    Mindus, Stephanie; Pawlowski, Jacek; Nisell, Magnus; Ferrara, Giovanni

    2013-01-01

    Medical treatment of pulmonary arterial hypertension (PAH) is increasingly common. Prostacyclins were introduced in the early 90s, and treprostinil is one of the most frequently used drugs of this class today, owing to its long half-life and to the possibility to administer the molecule through several routes. Treprostinil is considered a safe drug and is associated with a significant improvement of exercise capacity, especially in patients with idiopathic PAH (iPAH). Systemic sclerosis-associated PAH (sc-PAH) correlates to a worse prognosis compared with that of iPAH. Despite these considerations, safety data on treprostinil are still limited and mainly derived from randomised controlled trials and retrospective studies with relatively small and heterogeneous cohorts of patients with PAH. We report the occurrence of a severe intra-abdominal bleeding during treprostinil infusion in a patient with sc-PAH. PMID:23446048

  19. Influence of colloid infusion on coagulation during off-pump coronary artery bypass grafting

    PubMed Central

    Muralidhar, K; Garg, Rajnish; Mohanty, SK; Banakal, Sanjay

    2010-01-01

    This study was conducted to determine the influence of colloid infusion on coagulation in patients undergoing off-pump coronary artery bypass grafting (OP-CABG). Thirty patients undergoing elective OP-CABG received medium molecular weight hydroxyethyl starch group I (MMW-HES 200/0.5), low molecular weight hydroxyethyl starch group II (LMW-HES 130/0.4) or gelatin group III (GEL) in a prospective randomized trial. Blood samples were assessed for hemoglobin (Hb), activated coagulation time (ACT), prothrombin time (PT), activated partial thromboplastin time (aPPT), platelet count, fibrinogen and von Willebrand factor (vWF) at specified intervals. Total volume of the colloid infused and postoperative chest-time drainage was also measured. There was a significant decrease in Hb, platelet count, fibrinogen levels in all these groups, which did not warrant blood transfusion. After the colloid infusion, vWF decreased significantly to 67% from baseline in group I as compared to 85 and 79% in group II and group III, respectively. vWF levels remained lower than the baseline value in the first 24 hours in group I, whereas this factor level increased above the baseline values in groups II and III, 6 hours postoperatively. Postoperative chest tube drainage in 24 hours was significantly higher in group I (856 ± 131 ml) as compared to group II (550 ± 124 ml) and group III (582 ± 159 ml). LMW-HES 130/0.4 was superior to MMW-HES 200/0.5 and gelatin in patients undergoing OP-CABG, in terms of better preservation of coagulation associated with enhanced volume effect. PMID:20661354

  20. [Intra-arterial fibrinolytic therapy for acute mesenteric ischemia].

    PubMed

    Michel, C; Laffy, P; Leblanc, G; Riou, J Y; Chaloum, S; Maklouf, M; Le Guen, O; Pitre, J

    2001-01-01

    We report a case of mesenteric ischemia secondary to embolic occlusion treated by percutaneous intra-arterial thrombolysis. Early initial radiographic evaluation included abdominal plain film, ultrasonography, abdominal CT, and arteriography. Only selective superior mesenteric artery angiography provided definite diagnosis. The duration of ischemic symptoms before thrombolysis was 6 hours. Post procedure angiogram at 12 hours showed complete resolution of the mesenteric arterial thrombus with clinical improvement. The most important criteria for patient survival is early diagnosis and immediate treatment. Direct infusion of urokinase into the superior mesentric artery may be an alternative to surgery in selected patients and particularly in patients without evidence of frank bowel necrosis. PMID:11223630

  1. Transcatheter Arterial Infusion Therapy in the Treatment of Advanced Pancreatic Cancer: A Feasibility Study

    SciTech Connect

    Shibuya, Keiko; Nagata, Yasushi; Itoh, Tuyoshi; Okajima, Kaoru; Murata, Rumi; Takagi, Takehisa; Hiraoka, Masahiro

    1999-05-15

    Purpose: To evaluate the effects of transcatheter arterial infusion (TAI) therapy in 18 patients with advanced pancreatic cancer. Methods: The drugs infused were epirubicin 60 mg, mitomycin C 20 mg, and 5-fluorouracil 500 mg. The efficacy of TAI was evaluated by a tumor marker (CA19-9), computed tomography (CT) findings, and postoperative histopathological specimens. Results: In 10 of 15 cases, the tumor marker level was decreased after TAI therapy. In 6 of 14 cases, CT showed a decrease in the tumor size, and in 1 case, the tumor disappeared completely. In 6 cases the tumor could be resected. Necrosis, fibrosis, and degeneration of cancer cells were seen in 3 of 4 cases for whom a histopathological evaluation was done. The median survival was 11 months. In 17 patients back pain was the chief complaint, and was reduced to a self-controlled level in 10 patients following TAI therapy. No major complications were encountered. Conclusion: TAI appears to be an effective palliative treatment for advanced pancreatic cancer.

  2. Efficacy of Intra-Arterial Infusion Chemotherapy for Head and Neck Cancers Using Coaxial Catheter Technique: Initial Experience

    SciTech Connect

    Tsurumaru, Daisuke Kuroiwa, Toshiro; Yabuuchi, Hidetake; Hirata, Hideki; Higaki, Yuichiro; Tomita, Kichinobu

    2007-04-15

    The aim of this study was to evaluate the efficacy of intra-arterial infusion chemotherapy for head and neck cancers using a coaxial catheter technique: the superficial temporal artery (STA)-coaxial catheter method. Thirty-one patients (21 males and 10 females; 37-83 years of age) with squamous cell carcinoma of the head and neck (maxilla, 2; epipharynx, 4; mesopharynx, 8; oral floor, 4; tongue, 10; lower gingiva, 1; buccal mucosa, 2) were treated by intra-arterial infusion chemotherapy. Four patients were excluded from the tumor-response evaluation because of a previous operation or impossibility of treatment due to catheter trouble. Forty-eight sessions of catheterization were performed. A guiding catheter was inserted into the STA and a microcatheter was advanced into the tumor-feeding artery via the guiding catheter under angiographic guidance. When the location of the tumor or its feeding artery was uncertain on angiography, computed tomographic angiography was performed. The anticancer agent carboplatin (CBDCA) was continuously injected for 24 h through the microcatheter from a portable infusion pump attached to the patient's waist. The total administration dose was 300-1300 mg per body. External radiotherapy was administered during intra-arterial chemotherapy at a total dose of 21-70.5 Gy.The initial response was complete response in 15 patients, partial response in 7 patients, and no change in 5 patients; the overall response rate was 81.5% (22/27). Complication-related catheter maintenance was observed in 15 of 48 sessions of catheterization. Injury and dislocation of the microcatheter occurred 10 times in 7 patients. Catheter infection was observed three times in each of two patients, and catheter occlusion and vasculitis occurred in two patients. Intra-arterial infusion chemotherapy via the STA-coaxial catheter method could have potential as a favorable treatment for head and neck tumors.

  3. Effective use of multi-arterial infusion chemotherapy for advanced non-small cell lung cancer patients: four clinical specified cases.

    PubMed

    Nakanishi, Masanori; Umeda, Yukihiro; Demura, Yoshiki; Ameshima, Shingo; Chiba, Yukio; Miyamori, Isamu; Ishizaki, Takeshi

    2007-02-01

    Arterial infusion chemotherapy is considered to be a treatment option for lung cancer patients who are intolerant of systemic chemotherapy because of an increased risk of severe toxicity. However, a number of major studies regarding arterial infusion chemotherapy for lung cancer have reported disappointing results. We performed arterial infusion chemotherapy for four patients with advanced NSCLC who were unable to receive systemic chemotherapy or radiotherapy. After detecting the feeding arteries precisely by angiography, low-dose chemotherapeutic agents were administrated into the corresponding arteries. In each case, multiple feeding arteries including main feeding arteries other than the bronchial artery were detected and a partial response (PR) was obtained without severe toxicity in all. We consider that the present method is an effective treatment option for lung cancer patients who are restricted from undergoing standard systemic chemotherapy or radiotherapy. PMID:17098326

  4. Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

    SciTech Connect

    Cao Wei; Li Jing; Wu Zhiqun; Zhou Changxi; Liu Xi; Wan Yi; Duan Yunyou

    2013-06-15

    Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 Degree-Sign C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 Degree-Sign C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

  5. N-acetylcysteine infusion reduces the resistance index of renal artery in the early stage of systemic sclerosis

    PubMed Central

    Rosato, Edoardo; Cianci, Rosario; Barbano, Biagio; Menghi, Ginevra; Gigante, Antonietta; Rossi, Carmelina; Zardi, Enrico M; Amoroso, Antonio; Pisarri, Simonetta; Salsano, Felice

    2009-01-01

    Aim: To evaluate resistance index (RI) changes in renal artery after N-acetylcysteine infusion in patients with systemic sclerosis. Methods: In an open-label study 40 patients with systemic sclerosis (SSc) were treated with N-acetylcysteine (NAC) iv infusion over 5 consecutive hours, at a dose of 0.015 g·kg−1·h−1. Renal haemodynamic effects were evaluated by color Doppler examination before and after NAC infusion. Results: NAC infusion significantly reduced RI in a group of sclerodermic patients with early/active capillaroscopic pattern, modified Rodnan Total Skin Score (mRTSS) <14 and mild-moderate score to the vascular domain of Medsger Scleroderma Disease Severity Scale (DSS). RI increased after NAC infusion in patients with late capillaroscopic pattern, mTRSS>14 and severe-end stage score to the vascular domain of DSS. In patients with reduction of RI after NAC infusion, diffusion capacity for carbon monoxide mean value was significantly higher than in those patients with an increase of RI. No significant differences in renal blood flow were found between patients with different subsets of SSc. Conclusion: In patients with low disease severity NAC ameliorates vascular renal function. PMID:19730428

  6. Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, O. Kusunoki, S.; Kudoh, K.; Takamori, H.; Tsuji, T.; Kanemitsu, K.; Yamashita, Y.

    2006-06-15

    Purpose. To evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma. Methods. CTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis. Results. A catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean {+-} SD, 8.8 {+-} 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05). Conclusion. In patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.

  7. Iatrogenic ascending aortic dissection following cannulation for arterial return and for infusion of cardioplegic solution: Prevention and repair

    PubMed Central

    Ugorji, Clement C.; Cooley, Denton A.; Norman, John C.

    1980-01-01

    Two patients are presented in whom dissection of the ascending aorta resulted from cannulation for arterial return and from the infusion of cardioplegic solution. The dissections were recognized promptly. Following dissection in the first patient, the femoral artery was used to reestablish systemic perfusion. The aortic valve and dissected ascending aorta were replaced, and three vessels were grafted. In the second patient, the dissected anterior wall of the ascending aorta was excised and replaced with a low-porosity Dacron patch into which the proximal aortocoronary anastomoses were inserted. Predisposing factors are discussed, along with preventive measures and methods of repair. PMID:15216287

  8. Arterial medial necrosis and hemorrhage induced in rats by intravenous infusion of fenoldopam mesylate, a dopaminergic vasodilator.

    PubMed Central

    Yuhas, E. M.; Morgan, D. G.; Arena, E.; Kupp, R. P.; Saunders, L. Z.; Lewis, H. B.

    1985-01-01

    Fenoldopam mesylate, a selective, postsynaptic, dopaminergic vasodilator, was administered to rats for assessment of its clinical, toxicologic, and pathologic effects. Groups of 8 male and 8 female rats received 5, 25, 50, or 100 micrograms/kg/min by intravenous infusion for 24 hours. Groups of 12 male and 12 female rats received 2, 8, 16, or 20 mg/kg/day by intravenous injection once daily for 12 days. Tissues were examined by light microscopy. Rats infused for 24-hours with 5-100 micrograms/kg/min of fenoldopam had lesions of renal and splanchnic arteries characterized by medial necrosis and hemorrhage. None were seen in control rats or those administered the compound by intravenous injection. Arteries with four to five layers of medial smooth-muscle cells were most severely and frequently affected. Lesions were particularly severe in interlobular pancreatic arteries and subserosal gastric arteries. They occurred first at 4 hours, were present at low incidence at 8 hours, were induced in unrestrained rats, and were not caused by the experimental procedures employed. The nature and disposition of this novel arterial lesion in the rat suggests that its pathogenesis may be related to the pharmacologic activity of fenoldopam mesylate at the dopamine receptor. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2858975

  9. The Analysis of Efficacy and Failure Factors of Uterine Artery Methotrexate Infusion and Embolization in Treatment of Cesarean Scar Pregnancy

    PubMed Central

    Ming, Xu; Li, Ke; Wang, Jingbing

    2013-01-01

    Objectives. This study observes therapeutic efficacy of uterine artery embolization combined with MTX infusion which terminates cesarean scar pregnancy (CSP) and induces three factors which probably relate to failure. Methods. Twenty-three CSP patients were treated with combined uterine artery MTX infusion and embolization. Among them six patients with severe hemorrhage were immediately treated with interventional operation. Clinical effects were estimated by symptoms, serum β-hCG, ultrasound, and MR. Results. Interventional treatments were technologically successful in 22 patients except one. Immediate hemostasis was achieved in all 6 patients with massive colporrhagia. No occurrence of infection and uterine necrosis was observed, but 12 women suffered abdominal pains. Nineteen patients' uteri were preserved, whereas four underwent hysterectomy eventually. Conclusions. Transcatheter arterial chemoembolization is effective to treat high-risk CSP in preference to hysterectomy. To achieve more successful outcomes, three factors should be highlighted: adequate MTX dosage, appropriate embolic material, and complete embolization of target arteries that supply blood to embryo in the scar. PMID:24282376

  10. Continuous regional arterial infusion for acute pancreatitis: a propensity score analysis using a nationwide administrative database

    PubMed Central

    2013-01-01

    Introduction Although continuous regional arterial infusion (CRAI) of a protease inhibitor and an antibiotic may be effective in patients with severe acute pancreatitis, CRAI has not yet been validated in large patient populations. We therefore evaluated the effectiveness of CRAI based on data from a national administrative database covering 1,032 Japanese hospitals. Methods In-hospital mortality, length of stay and costs were compared in the CRAI and non-CRAI groups, using propensity score analysis to adjust for treatment selection bias. Results A total of 17,415 eligible patients with acute pancreatitis were identified between 1 July and 30 September 2011, including 287 (1.6%) patients who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with well-balanced baseline characteristics. In-hospital mortality rates were similar in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence interval, 0.44–1.78, P = 0.720). CRAI was associated with significantly longer median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher rate of interventions for infectious complications, such as endoscopic/surgical necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061). Conclusions CRAI was not effective in reducing in-hospital mortality rate in patients with acute pancreatitis, but was associated with longer hospital stay and higher costs. Randomized controlled trials in large numbers of patients are required to further evaluate CRAI for this indication. PMID:24088324

  11. 5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved

    PubMed Central

    2012-01-01

    Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. The mesenteric vasculature was chosen as an ideal candidate for the site of 5-HT receptor mediated vascular relaxation given the high percentage of cardiac output the site receives. Real-time RT-PCR demonstrated that mRNA transcripts for the 5-HT2B, 5-HT1B, and 5-HT7 receptors are present in sham and DOCA-salt superior mesenteric arteries. Immunohistochemistry and Western blot validated the presence of the 5-HT2B, 5- HT1B and 5-HT7 receptor protein in sham and DOCA-salt superior mesenteric artery. Isometric contractile force was measured in endothelium-intact superior mesenteric artery and mesenteric resistance arteries in which the contractile 5- HT2A receptor was antagonized. Maximum concentrations of BW-723C86 (5- HT2B agonist), CP 93129 (5-HT1B agonist) or LP-44 (5-HT7 agonist) did not relax the superior mesenteric artery from DOCA-salt rats vs. vehicle. Additionally, 5-HT (10–9 M to 10–5 M) did not cause relaxation in either contracted mesenteric resistance arteries or superior mesenteric arteries from normotensive Sprague- Dawley rats. Thus, although 5-HT receptors known to mediate vascular relaxation are present in the superior mesenteric artery, they are not functional, and are therefore not likely involved in a 5-HT-induced fall in total peripheral resistance and MAP. PMID:22559843

  12. Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases

    SciTech Connect

    Mitsudo, Kenji; Koizumi, Toshiyuki; Iida, Masaki; Iwai, Toshinori; Oguri, Senri; Yamamoto, Noriyuki; Itoh, Yoshiyuki; Kioi, Mitomu; Hirota, Makoto; Tohnai, Iwai

    2012-08-01

    Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer. Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m{sup 2}; CDDP, total 100-150 mg/m{sup 2}) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks. Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively. Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3

  13. [Two long-term survival cases of unresectable intrahepatic cholangiocarcinoma treated with hepatic arterial infusion chemotherapy and radiation therapy].

    PubMed

    Komatsu, Hisateru; Kanazawa, Akishige; Tsukamoto, Tadashi; Shimizu, Sadatoshi; Ishikawa, Akira; Mori, Yoshihiro; Nakajima, Takayoshi; Ohira, Go; Kodai, Shintaro; Morimoto, Junya; Yamazoe, Sadaaki; Yamamoto, Atsushi; Inoue, Toru; Yamashita, Yoshito; Nishiguchi, Yukio; Ikehara, Teruyuki; Taira, Koichi; Horii, Katsuhiko; Yamazaki, Osamu

    2012-11-01

    The prognosis for patients with unresectable intrahepatic cholangiocarcinoma(ICC) is extremely poor. Case 1 was a 65- year-old woman who had an ICC of 9 cm in diameter (mass-forming type) in the right lobe with portal trunk invasion. She was treated with hepatic arterial infusion chemotherapy[cisplatin(CDDP)/5-fluorouracil(5-FU)/l-leucovorin(l-LV)] and radiation therapy (total dose, 50 Gy). After 6 months, abdominal computed tomography (CT) revealed that the tumor had regressed. She survived for 7 years without recurrence of the ICC; subsequently, she died of peritoneal cancer. Case 2 was a 59-year-old woman who had an ICC of 8 cm in diameter (mass-forming type) in the left lobe with lymph node metastasis in the hepatoduodenal ligament; the right hepatic artery was involved by the metastatic lymph nodes. She was treated with hepatic arterial infusion chemotherapy(CDDP/5-FU/l-LV) and radiation therapy(total dose, 30 Gy). After 10 months, abdominal CT revealed that the tumor had disappeared, but paraaortic and mediastinal lymph node metastases were detected. She was therefore treated with systemic chemotherapy. Treatment with systematic chemotherapy enabled her to survive for over 5 years with a good performance status. PMID:23267958

  14. Molecular-specific urokinase antibodies

    NASA Technical Reports Server (NTRS)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  15. Subtraction CT with Low-Flow-Rate Arterial Contrast Injection to Estimate Drug Distribution During Balloon-Occluded Arterial Chemotherapy Infusion for Bladder Cancer

    SciTech Connect

    Mori, Kensaku; Yoshioka, Hiroshi; Nakajima, Kotaro; Irie, Toshiyuki; Sugahara, Shinji; Nozawa, Kumiko; Saida, Yukihisa; Itai, Yuji; Ishikawa, Satoru; Hayashi, Hitoshi

    2000-03-15

    Purpose: To simulate drug distribution during balloon-occluded arterial chemotherapy infusion (BOAI) for urinary bladder cancer using subtraction computed tomography (CT) with low-flow-rate arterial contrast injection (S-CTLA).Methods: Ten patients with bladder cancer underwent S-CTLA, and the distribution of contrast agent during BOAI into both internal iliac arteries simultaneously was evaluated in nine pairs of internal iliac arteries and one single artery. For S-CTLA, spiral CT data were acquired before and after 0.2 ml/sec intraarterial injection of contrast material. The enhancement of the urinary bladder wall, the gluteal muscles, and the pelvic bones was categorized using a 4-grade scale. The grades were compared in each of the three pelvic components and differences were tested for significance using the Wilcoxon test for paired groups.Results: S-CTLA revealed the distribution of the contrast agent clearly. Gluteal muscles grades were significantly higher than those of the other two assessed components.Conclusion: BOAI does not improve the concentration of contrast agent to the bladder wall over neighboring structures, suggesting that the balloon occlusion technique does not achieve its desired goal for chemotherapy targeting.

  16. Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

    PubMed Central

    Witkowski, Maria Carolina; de Moraes, Maria Antonieta P.; Firpo, Cora Maria F.

    2013-01-01

    OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031]. PMID:24473958

  17. Organ Preservation With Daily Concurrent Chemoradiotherapy Using Superselective Intra-Arterial Infusion via a Superficial Temporal Artery for T3 and T4 Head and Neck Cancer

    SciTech Connect

    Mitsudo, Kenji; Shigetomi, Toshio; Fujimoto, Yasushi; Nishiguchi, Hiroaki; Yamamoto, Noriyuki; Furue, Hiroki; Ueda, Minoru; Itoh, Yoshiyuki; Fuwa, Nobukazu; Tohnai, Iwai

    2011-04-01

    Purpose: To evaluate the therapeutic results and rate of organ preservation in patients with advanced head and neck cancer treated with superselective intra-arterial chemotherapy via a superficial temporal artery and daily concurrent radiotherapy. Methods and Materials: Between April 2002 and March 2006, 30 patients with T3 or T4a squamous cell carcinoma of the head and neck underwent intra-arterial chemoradiotherapy. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m{sup 2}; cisplatin, total 150 mg/m{sup 2}) and daily concurrent radiotherapy (total, 60 Gy) for 6 weeks. Results: The median follow-up for all patients was 46.2 months (range, 10-90 months). The median follow-up for living patients was 49.7 months (range, 36-90 months). After intra-arterial chemoradiotherapy was administered, primary site complete response was achieved in 30 (100%) of 30 cases. Seven patients (23.3%) died. Using the Kaplan-Meier method, 1-year, 3-year, and 5-year survival rates were 96.7%, 83.1%, and 70.2%, respectively, while 1-year, 3-year, and 5-year local control rates were 83.3%, 79.7%, and 73.0%, respectively. Grade 3 or 4 mucositis occurred in 20 cases (66.7%). Grade 3 toxicities included dysphagia in 20 cases (66.7%), dermatitis in 6 cases (20%), nausea/vomiting in 2 cases (6.7%), and neutropenia and thrombocytopenia in 1 case (3.3%). No osteoradionecrosis of mandible and maxillary bones developed during follow-up. Conclusions: Intra-arterial chemoradiotherapy using a superficial temporal artery provided good overall survival and local control rates. This combination chemoradiotherapy approach can preserve organs and minimize functional disturbance, thus contributing to patients' quality of life.

  18. Rapid Fatty Acid Ethyl Ester Synthesis by Porcine Myocardium Upon Ethanol Infusion into the Left Anterior Descending Coronary Artery

    PubMed Central

    Yoerger, Danita M.; Best, Catherine A.; McQuillan, Brendan M.; Supple, Gregory E.; Guererro, J. Luis; Cluette-Brown, Joanne E.; Hasaba, Ali; Picard, Michael H.; Stone, James R.; Laposata, Michael

    2006-01-01

    Fatty acid ethyl esters (FAEEs), nonoxidative metabolites of ethanol, have been implicated in ethanol-induced heart injury. To assess the in vivo production of FAEEs by myocardial tissue, we used a modified ethanol ablation procedure in pigs. A controlled 60-minute ethanol infusion was administered into the distal left anterior descending coronary artery in seven swine; serial blood sampling of the coronary sinus and peripheral vein before, during, and after infusion allowed measurement of FAEE production and ethanol levels in the coronary sinus and the peripheral circulation. In a single animal, FAEEs were also quantified from nine different sites within the myocardium. FAEEs were produced by the heart within 5 minutes of exposure to ethanol, with very high concentrations of FAEEs detected in coronary sinus blood. Significant variability in amounts of FAEEs was detected in different regions of the heart tissue. A strong correlation was found between coronary sinus FAEEs and ethanol concentration (r = 0.9241, P < 0.00001). FAEE production by the heart after delivery of ethanol into the left anterior descending coronary artery was rapid, reaching levels in the coronary sinus blood 4 to 10 times greater than that found in peripheral blood after ethanol intake. These data demonstrate that FAEEs may be mediators of ethanol-induced cardiotoxicity. PMID:16651611

  19. Hepatic resection, hepatic arterial infusion pump therapy, and genetic biomarkers in the management of hepatic metastases from colorectal cancer

    PubMed Central

    McAuliffe, John C.; Qadan, Motaz

    2015-01-01

    The liver is the most common site of colorectal cancer metastasis. Fortunately, improvements have been made in the care of patients with colorectal liver metastasis (CRLM). Effective management of CRLM requires a multidisciplinary approach that is tailored to individuals in order to achieve long-term survival, and cure. Resection and systemic chemotherapy provides benefit in selected individuals. An adjunct to resection and/or systemic chemotherapy is the use of hepatic arterial infusion pump (HAIP) therapy. Many studies show HAIP provides benefit for select patients with CRLM. Added to the crucible of a multidisciplinary approach to managing CRLM is the ever growing understanding of tumor biology and genetic profiling. In this review, we discuss the outcomes of resection, systemic therapies and HAIP therapy for CRLM. We also discuss the impact of recent advances in genetic profiling and mutational analysis, namely mutation of KRAS and BRAF, for this disease. PMID:26697204

  20. Compatibility of carbapenem antibiotics with nafamostat mesilate in arterial infusion therapy for severe acute pancreatitis: stabilities of carbapenem antibiotics.

    PubMed

    Hamada, Yukihiro; Imaizumi, Hiroshi; Miyazawa, Shirou; Kida, Mitsuhiro; Souma, Kazui; Koizumi, Wasaburou; Sunakawa, Keisuke; Kuroyama, Masakazu

    2012-08-01

    The effectiveness of continuous regional arterial infusion therapy using protease inhibitors and antibiotics for severe acute pancreatitis has been previously reported. Carbapenem antibiotics, which have a broad antibacterial spectrum, and nafamostat mesilate are often used for this therapeutic approach. We investigated the compatibility of various carbapenem antibiotics with nafamostat mesilate. Carbapenem antibiotics were dissolved in 30 mL of saline or 5% glucose and the appearance, pH, and stability of the solutions were determined. The changes in each carbapenem antibiotic solution after mixing with nafamostat mesilate were then investigated. Biapenem and doripenem showed a residual rate of > or = 90% at 8 hours after dissolution in saline or 5% glucose and exhibited an appropriate appearance and residual rate (> or = 90%). After mixing with nafamostat mesilate, biapenem maintained a residual rate of > or = 90% for the longest time period (8 hours) and exhibited a slight coloration, followed by doripenem (6 hours) and meropenem dissolved in saline. The other carbapenem antibiotics that were tested exhibited changes in appearance or their residual rate. Biapenem and doripenem, which exert their effects in a time-dependent manner, can be infused for prolonged periods for the treatment of not only severe acute pancreatitis, but also other severe infections. PMID:23259254

  1. Limb cooling with targeted arterial infusion of cold fluid alleviates scald injury: an experimental rabbit study

    PubMed Central

    Guan, Hao; Zhao, Zhijing; Zhou, Qin; He, Fei; Yu, Min; Cai, Weixia; Yang, Ximing; Xu, Zhigang; Hou, Hongyi; Hu, Dahai

    2014-01-01

    Background: To investigate the cooling and healing effect of different modalities: Hydrogel dressing® was compared with targeted artery injection of low temperature liquid as a coolant following application to a fresh deep partial thickness hot water scald in a rabbit hind limb model. Materials and methods: Fifty five rabbits were randomly divided into 5 groups. Treatment group received femoral artery injection of low temperature liquid and hydrogel dressing post burn 30 min or 1 hour. Control group were just scalded. Subcutaneous (Tu) and deep mussel temperatures (Tm) were continually monitored in all wounds. After scald the rectal temperature were detected within 6 hours. The wounds were biopsied for histological assessment at 72 h and 3 weeks. Results: Effective cooling of the burn wound and an increased rate of wound healing was achieved by both treatment methods. The final temperature at 1h decreased to the preburn temperature. Compared with hydrogel dressing group (Tm decreased by 1.3 ± 0.4°C), Tm decreased by 2.8 ± 0.3°C in femoral artery injection group, showing significant difference (P < 0.05). Artery injection of low temperature liquid and hydrogel dressing almost exert no influence on rabbit core temperature. Clinical and histological assessment at 21 days indicated more rapid healing in both the 30 min hydrogel dressing and artery injection burns compared with the controls and the 60 minutes intervention groups. Conclusion: This result indicates artery injection of low temperature liquid earlier to cooling limb is an effective means to reduce residual heat damage tissue without affect core temperature and increase wound healing. PMID:25356176

  2. Intra-arterial Methylprednisolone Infusion in Treatment-Resistant Graft-Versus-Host Disease

    SciTech Connect

    Weintraub, Joshua L. Belanger, Adam R.; Sung, Chris C.; Stangl, P. Anondo; Nowakowski, F. Scott; Lookstein, Robert L.

    2010-06-15

    Acute graft-versus-host disease (GVHD) is a potentially fatal complication following allogeneic hematopoietic stem cell transplant. Standard primary therapy for acute GVHD includes systemic steroids, often in combination with other agents. Unfortunately, primary treatment failure is common and carries a high mortality. There is no generally accepted secondary therapy for acute GVHD. Although few data on localized therapy for GVHD have been published, intra-arterial injection of high-dose corticosteroids may be a viable option. We treated 11 patients with steroid-resistant GVHD using a single administration of intra-arterial high-dose methylprednisolone. Three patients (27%) died periprocedurally. Four patients (36%) had a partial response to intra-arterial treatment and were discharged on total parenteral nutrition and oral medication. Four patients (36%) had a complete response and were discharged on oral diet and oral medication. No immediate treatment or procedure-related complications were noted. Twenty-seven percent of patients survived long-term. Our preliminary results suggest that regional intra-arterial treatment of steroid-resistant GVHD is a safe and potentially viable secondary therapy in primary treatment-resistant GVHD.

  3. A method for recording effects of anti-epileptic drugs on interictal discharge in the cat's cerebral cortex. Factors determining the distribution of external carotid artery infusions.

    PubMed

    Landgren, S; Selstam, G; Aasly, J; Danielsson, E

    1986-11-01

    The method utilizes infusion via the external carotid (ECA), the internal maxillary arteries and their anastomoses to the cerebral circulation. It takes into account the ipsilateral distribution of the carotid blood supply. A regular interictal epileptiform spiking from foci on both hemispheres was provided by local application to the cortical surface of small pieces of filter paper soaked in sodium benzylpenicillin, 100,000 IE ml-1. The infused drug affects the ipsilateral foci, and the contralateral one functions as a simultaneous untreated control. The stability of the interictal frequency and the effect of non-oxygen carrying solvents are described. The effect of changes in blood pressure, temperature and PCO2 are considered as well as the coupling between activity in ipsi- and contralateral foci. Experiments with infused radioactive microspheres were performed to determine the strictness of the ipsilateral distribution and the conditions under which it was upheld. With mean arterial blood pressures between 70 mm Hg and 170 mm Hg and infusion speeds between 1.0 ml min-1 and 6.3 ml min-1 the distribution to the contralateral cerebral hemisphere was 0.3% (SD 0.2, SEM 0.1). Infusions of [125I]albumin were used to determine the blood flow in ECA. The flow varied between 20 ml min-1 and 68 ml min-1. The higher values were seen when the extracerebral shunting was high. Conditions influencing the dilution of the infusion and its distribution within the brain were investigated. Important factors were carotid and cerebral blood flow, arterial blood pressure, speed and duration of the infusion, recirculation and cerebral temperature. Arterial PCO2, pH and PO2 should be carefully controlled. Computer-supported treatment of interictal spike frequency and amplitude, as well as of circulatory and respiratory parameters, was utilized. The method was tested in experiments with infusions of 5 alpha-pregnanolone. It was shown that infusions, shorter than the estimated

  4. [Pre-Operative Treatment with Transcatheter Arterial Chemoembolization (TACE) and Hepatic Arterial Infusion (HAI) for Liver Metastasis from Gastric Cancer--A Case Report].

    PubMed

    Tanigawa, Takahiko; Hasuike, Yasunori; Akiyama, Yousuke; Higuchi, Ichiro; Ishikawa, Akira; Okada, Atsuya; Miyamoto, Makoto

    2015-11-01

    The patient was an 83-year-old man who underwent distal gastrectomy for gastric cancer (T3, N1, M0, P0, M0, stage ⅡB) at a different hospital from ours. A metastatic lesion was detected in the liver 5 months after gastrectomy. Although chemotherapy with S-1 or bi-weekly CPT-11 was administered for 6 months, the liver tumor increased in size. The patient was referred to our hospital for treatment of the liver metastasis. Abdominal-computed tomography (CT) and magnetic resonance imaging (MRI) revealed a solitary metastatic liver tumor (9 cm in diameter: S7/S6/S8) with a hypervascular tumor stain. Transcatheter arterial chemoembolization (TACE) using degradable starch microspheres (DSM) plus mitomycin C, and hepatic arterial infusion (HAI) using high-dose 5-fluorouracil (5-FU) (6,000 mg/week), were performed 54 days before curative resection of the liver (S6+S7+S8+S5b/c). Histological findings revealed metastatic adenocarcinoma with a tumor thrombus in the posterior branch of the portal vein. The patient was treated with 2 courses of adjuvant chemotherapy with paclitaxel. No recurrence was observed 8 months after hepatectomy. This case suggests that combined treatment with TACE/HAI as a multimodal treatment might be effective in the management of hypervascular liver metastasis from gastric cancer. PMID:26805063

  5. Deriving the Intrahepatic Arteriovenous Shunt Rate from CT Images and Biochemical Data Instead of from Arterial Perfusion Scintigraphy in Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Ozaki, Toshiro Seki, Hiroshi; Shiina, Makoto

    2009-09-15

    The purpose of the present study was to elucidate a method for predicting the intrahepatic arteriovenous shunt rate from computed tomography (CT) images and biochemical data, instead of from arterial perfusion scintigraphy, because adverse exacerbated systemic effects may be induced in cases where a high shunt rate exists. CT and arterial perfusion scintigraphy were performed in patients with liver metastases from gastric or colorectal cancer. Biochemical data and tumor marker levels of 33 enrolled patients were measured. The results were statistically verified by multiple regression analysis. The total metastatic hepatic tumor volume (V{sub metastasized}), residual hepatic parenchyma volume (V{sub residual}; calculated from CT images), and biochemical data were treated as independent variables; the intrahepatic arteriovenous (IHAV) shunt rate (calculated from scintigraphy) was treated as a dependent variable. The IHAV shunt rate was 15.1 {+-} 11.9%. Based on the correlation matrixes, the best correlation coefficient of 0.84 was established between the IHAV shunt rate and V{sub metastasized} (p < 0.01). In the multiple regression analysis with the IHAV shunt rate as the dependent variable, the coefficient of determination (R{sup 2}) was 0.75, which was significant at the 0.1% level with two significant independent variables (V{sub metastasized} and V{sub residual}). The standardized regression coefficients ({beta}) of V{sub metastasized} and V{sub residual} were significant at the 0.1 and 5% levels, respectively. Based on this result, we can obtain a predicted value of IHAV shunt rate (p < 0.001) using CT images. When a high shunt rate was predicted, beneficial and consistent clinical monitoring can be initiated in, for example, hepatic arterial infusion chemotherapy.

  6. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA[S

    PubMed Central

    Kootte, Ruud S.; Smits, Loek P.; van der Valk, Fleur M.; Dasseux, Jean-Louis; Keyserling, Constance H.; Barbaras, Ronald; Paolini, John F.; Santos, Raul D.; van Dijk, Theo H.; Dallinga-van Thie, Geesje M.; Nederveen, Aart J.; Mulder, Willem J. M.; Hovingh, G. Kees; Kastelein, John J. P.; Groen, Albert K.; Stroes, Erik S.

    2015-01-01

    Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8–29.1] mg/dl; apoA-I, 28.7 [7.9–59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm2 (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. PMID:25561459

  7. Effect of open-label infusion of an apoA-I-containing particle (CER-001) on RCT and artery wall thickness in patients with FHA.

    PubMed

    Kootte, Ruud S; Smits, Loek P; van der Valk, Fleur M; Dasseux, Jean-Louis; Keyserling, Constance H; Barbaras, Ronald; Paolini, John F; Santos, Raul D; van Dijk, Theo H; Dallinga-van Thie, Geesje M; Nederveen, Aart J; Mulder, Willem J M; Hovingh, G Kees; Kastelein, John J P; Groen, Albert K; Stroes, Erik S

    2015-03-01

    Reverse cholesterol transport (RCT) contributes to the anti-atherogenic effects of HDL. Patients with the orphan disease, familial hypoalphalipoproteinemia (FHA), are characterized by decreased tissue cholesterol removal and an increased atherogenic burden. We performed an open-label uncontrolled proof-of-concept study to evaluate the effect of infusions with a human apoA-I-containing HDL-mimetic particle (CER-001) on RCT and the arterial vessel wall in FHA. Subjects received 20 infusions of CER-001 (8 mg/kg) during 6 months. Efficacy was assessed by measuring (apo)lipoproteins, plasma-mediated cellular cholesterol efflux, fecal sterol excretion (FSE), and carotid artery wall dimension by MRI and artery wall inflammation by (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography scans. We included seven FHA patients: HDL-cholesterol (HDL-c), 13.8 [1.8-29.1] mg/dl; apoA-I, 28.7 [7.9-59.1] mg/dl. Following nine infusions in 1 month, apoA-I and HDL-c increased directly after infusion by 27.0 and 16.1 mg/dl (P = 0.018). CER-001 induced a 44% relative increase (P = 0.018) in in vitro cellular cholesterol efflux with a trend toward increased FSE (P = 0.068). After nine infusions of CER-001, carotid mean vessel wall area decreased compared with baseline from 25.0 to 22.8 mm(2) (P = 0.043) and target-to-background ratio from 2.04 to 1.81 (P = 0.046). In FHA-subjects, CER-001 stimulates cholesterol mobilization and reduces artery wall dimension and inflammation, supporting further evaluation of CER-001 in FHA patients. PMID:25561459

  8. Coronary artery bypass grafting in a patient with hemophilia B: continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy.

    PubMed

    Suzuki, Tomoyuki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Adachi, Osamu; Kanda, Keisuke; Ishikawa, Masaaki; Okitsu, Yoko; Harigae, Hideo; Kurosawa, Shin; Saiki, Yoshikatsu

    2016-08-01

    We herein report our experience of successfully managing the hemostatic system by controlling serum factor IX levels throughout the perioperative period in a patient with hemophilia B. Coronary artery bypass grafting with cardiopulmonary bypass was planned for a 52-year-old man with moderate severity of hemophilia B. During surgery, recombinant factor IX (rFIX; BeneFIX(®) Pfizer Japan inc., Tokyo, Japan) was administered by bolus infusion followed by continuous infusion as per the guidelines of the Japanese Society on Thrombosis and Hemostasis. The operative course was uneventful without any considerable bleeding or complications. PMID:25523881

  9. Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in patients with peripheral arterial disease

    PubMed Central

    Kunisawa, Takayuki; Yamagishi, Akio; Suno, Manabu; Nakade, Susumu; Honda, Naoki; Kurosawa, Atsushi; Sugawara, Ami; Tasaki, Yoshikazu; Iwasaki, Hiroshi

    2015-01-01

    Purpose We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease. Methods Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM). Results The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model. Conclusion The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively. PMID:25653534

  10. VASCULAR LESIONS AND S-THROMBOMODULIN CONCENTRATIONS FROM AURICULAR ARTERIES OF RABBITS INFUSED WITH MICROBUBBLE CONTRAST AGENT AND EXPOSED TO PULSED ULTRASOUND

    PubMed Central

    Zachary, James F.; Blue, James P.; Miller, Rita J.; O’Brien, William D.

    2007-01-01

    Arterial injury resulting from the interaction of contrast agent (CA) with ultrasound (US) was studied in rabbit auricular arteries and assessed by histopathologic evaluation and s-thrombomodulin concentrations. Three sites on each artery were exposed (2.8 MHz, 5-min exposure duration, 10-Hz pulse repetition frequency, 1.4-μs pulse duration) using one of three in situ peak rarefactional pressures (0.85, 3.9 or 9.5 MPa). Saline, saline/CA, and saline/US infusion groups (n = 28) did not have histopathologic damage. The saline/CA/US infusion group (n = 10) at exposure conditions below the FDA mechanical index limit of 1.9 did not have histopathologic damage, whereas the saline/CA/US infusion group (n = 9) at exposure conditions above the FDA limit did have damage (5 of 9 arteries). Lesions were characteristic of acute coagulative necrosis. Mean s-thrombomodulin concentrations, a marker for endothelial cell injury, were highest in rabbits exposed to US at 0.85 and 3.9 MPa, suggesting that vascular injury may be physiological and not accompanied by irreversible cellular injury. PMID:17112964

  11. Thrombolytic Therapy Using Urokinase for Management of Central Venous Catheter Thrombosis

    PubMed Central

    Son, Jung Tack; Min, Sun Young; Kim, Jae Il; Choi, Pyong Wha; Heo, Tae Gil; Lee, Myung Soo; Kim, Chul-Nam; Kim, Hong-Yong; Yi, Seong Yoon; Lee, Hye Ran; Roh, Young-Nam

    2014-01-01

    Purpose: The management of central venous catheters (CVCs) and catheter thrombosis vary among centers, and the efficacy of the methods of management of catheter thrombosis in CVCs is rarely reported. We investigated the efficacy of bedside thrombolysis with urokinase for the management of catheter thrombosis. Materials and Methods: We retrospectively reviewed data from patients who had undergone CVC insertion by a single surgeon in a single center between April 2012 and June 2014. We used a protocol for the management of CVCs and when catheter thrombosis was confirmed, 5,000 U urokinase was infused into the catheter. Results: A total of 137 CVCs were inserted in 126 patients. The most common catheter-related complication was thrombosis (12, 8.8%) followed by infection (8, 5.8%). Nine of the 12 patients (75%) with catheter thrombosis were recanalized successfully with urokinase. The rate of CVC recanalization was higher in the peripherally inserted central catheter (PICC) group (87.5%) than the chemoport group (50%). Reintervention for catheter-related thrombosis was needed in only 2.2% of patients when thrombolytic therapy using urokinase was applied. Age <60 years (P=0.035), PICC group (P=0.037) and location of the catheter tip above the superior vena cava (P=0.044) were confirmed as independent risk factors for catheter thrombosis. Conclusion: Thrombolysis therapy using urokinase could successfully manage CVC thrombosis. Reintervention was rarely needed when a protocol using urokinase was applied for the management of CVC thromboses. PMID:26217634

  12. A Multi-center Phase I Dose Escalation Trial to Evaluate Safety and Tolerability of Intra-arterial Temozolomide for Patients with Advanced Extremity Melanoma Using Normothermic Isolated Limb Infusion

    PubMed Central

    Beasley, Georgia M.; Speicher, Paul; Augustine, Christina K.; Dolber, Paul C.; Peterson, Bercedis L.; Sharma, Ketan; Mosca, Paul J.; Royal, Richard; Ross, Merrick; Zager, Jonathan S.; Tyler, Douglas S.

    2015-01-01

    Synopsis This phase I trial reports the first use of intra arterial temozolomide via isolated limb infusion for patients with advanced extremity melanoma. There was minimal toxicity and the maximum tolerated dose was determined. PMID:25145500

  13. [An effective case of hepatic arterial infusion chemotherapy based on biochemical modulation for hepatic recurrence of non-functioning islet cell carcinoma of the pancreas].

    PubMed

    Nishijima, K; Ohta, T; Elnemr, A; Yi, S; Ninomiya, I; Kitagawa, H; Fushida, S; Nishimura, G; Fujimura, T; Kayahara, M; Shimizu, K; Miwa, K

    2000-10-01

    A 55-year-old man had a metastasis in segment 3 of the liver 5 months after surgery for non-functioning islet cell carcinoma of the pancreas. The metastatic lesion increased in size in a short period, and other liver micro-metastases that could not be detected by imaging may exist, so hepatic arterial infusion chemotherapy was scheduled for 3 months. The patient underwent hepatic arterial infusion chemotherapy of 5-fluorouracil (250 mg/day/body for 5 days/week) and adriamycin (10 mg/day/body for 2 days/week) and cisplatin (10 mg/day/body for 5 days/week) and he was put on Leucovorin 30 mg/day as a biochemical modulator of 5-FU and tamoxifen 40 mg/day as a biochemical modulator of ADM. A total 6,000 mg of 5-FU, 100 mg of ADM and 240 mg of CDDP had been administered, until hepatic arterial infusion chemotherapy was discontinued because of complicated gastric ulcer. Three months later, the size of the metastatic liver tumor was reduced remarkably and no other metastasis was detected on CT scan, so he underwent partial hepatectomy of the metastatic lesion. No recurrence was found and he has survived in good physical condition during the follow-up period of 5 months after the second operation. PMID:11086447

  14. Effect of time duration of ruminal urea infusions on ruminal ammonia concentrations and portal-drained visceral extraction of arterial urea-N in lactating Holstein cows.

    PubMed

    Røjen, B A; Kristensen, N B

    2012-03-01

    The effects of a 6 versus 24h ruminal urea infusion in lactating dairy cows fed a basal diet deficient in N on ruminal ammonia concentration, arterial urea-N concentration, net portal-drained viscera (PDV) urea-N flux, arterial urea-N extraction across the PDV, and renal urea-N kinetics were investigated. Three Danish Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in major splanchnic blood vessels were randomly allocated to a 3 × 3 Latin square design with 21-d periods. Treatments were ventral ruminal infusion of water for 24h (water INF), 24-h infusion of 15 g of urea/kg of dry matter intake (DMI; 24-h INF), and 6-h infusion of 15 g of urea/kg of DMI (6-h INF). The 6-h INF was initiated 0.5h after the afternoon feeding, and ran until 2230 h. Eight sample sets of arterial, portal, and hepatic blood, ruminal fluid, and urine were obtained at 0.5h before the morning feeding and 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5h after feeding (i.e., 9 to 15.5h after the 6h infusion was terminated). A substantial decrease in DMI for 6-h INF compared with 24-h INF and water INF was observed, and it has to be recognized that DMI may have confounding effects. However, the experimental setting plan was met (i.e., to cause changes in the daily pattern of ruminal ammonia and blood urea-N concentrations). The arterial urea-N concentration for 24-h INF and 6-h INF were greater than the arterial urea-N concentration with water INF throughout the sampling window. However, the arterial urea-N concentration for 6-h INF decreased steadily with sampling time reflecting a carryover effect from the ruminal urea infusion. The ruminal ammonia concentration and net portal flux of ammonia for 6-h INF were not different from water INF; hence, no carryover effect on ruminal ammonia concentration was observed. The portal flux of urea-N was not affected by treatment (i.e., even the combination of low ruminal ammonia and high arterial urea-N concentration with 6-h INF was

  15. The Importance of Lamivudine Therapy in Liver Cirrhosis Patients Related HBV with Advanced Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy

    PubMed Central

    Momiyama, Koichi; Nagai, Hidenari; Ogino, Yu; Mukouzu, Takanori; Matsui, Daigo; Kogame, Michio; Matsui, Teppei; Wakui, Noritaka; Shinohara, Mie; Igarashi, Yoshinori; Sumino, Yasukiyo

    2015-01-01

    Purpose: We have previously reported that continuous hepatic arterial infusion chemotherapy (HAIC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with liver cirrhosis (LC) related to HCV infection (C-LC) or alcohol abuse (A-LC) than in patients who had LC related to HBV infection (B-LC). The aim of the present study was to retrospectively assess the efficacy of lamivudine therapy for B-LC patients with aHCC undergoing HAIC. Methods: Seventeen adult Japanese B-LC patients with aHCC were treated by HAIC with or without lamivudine (100 mg/day) between 2002 and 2008 at our hospital. Their tumors were inoperable according to computed tomography findings. HAIC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was given via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. Results: Nine of the 17 patients received lamivudine at a dose of 100 mg/day together with HAIC (LAM group), while 8 patients did not receive lamivudine and only had HAIC (non-LAM group). The response rate was 12.5 in the non-LAM group and 0.0% in the LAM group. However, the survival of the LAM group was better than that of the non-LAM group, although there was no significant difference between them. The median survival time of the LAM and non-LAM groups was 310 and 157 days, respectively. HBV-DNA levels were significantly lower after chemotherapy compared with that before chemotherapy in the LAM group. In the non-LAM group, the percentage of Th2 cells before HAIC and after HAIC was significantly higher than in the control group. However, the percentage of Th2 cells in the LAM group after HAIC was not different from that in the control group, although it was significantly higher in the LAM group than in the control group before chemotherapy. Conclusions: These results indicate that lamivudine therapy may prolong the survival of B-LC patients receiving HAIC for aHCC by reducing HBV

  16. Intra-Arterial Infusion Chemotherapy Using Cisplatin With Radiotherapy for Stage III Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Kaneyasu, Yuko Nagai, Nobutaka; Nagata, Yasushi; Hashimoto, Yasutoshi; Yuki, Shintaro; Murakami, Yuji; Kenjo, Masahiro; Kakizawa, Hideaki; Toyota, Naoyuki; Fujiwara, Hisaya; Kudo, Yoshiki; Ito, Katsuhide

    2009-10-01

    Purpose: To examine the effectiveness of concomitant intra-arterial infusion chemotherapy (IAIC) using cisplatin (CDDP) with radiotherapy for Stage III squamous cell carcinoma of the cervix. Materials and Methods: We analyzed 29 cases of Stage III squamous cell carcinoma of the uterine cervix treated with radiotherapy and IAIC of CDDP from 1991 to 2006. External-beam therapy was given to the whole pelvis using four opposing parallel fields with an 18-MV linear accelerator unit. A central shield was used after 30-40 Gy with external whole-pelvic irradiation, and the total dose was 50 Gy. High-dose-rate brachytherapy was given with {sup 192}Ir microSelectron. The dose at Point A was 6 Gy per fraction, 2 fractions per week, and the total number of fractions was either 3 or 4. Two or three courses of IAIC were given concomitantly with CDDP 120 mg or carboplatin 300 mg. Results: We confirmed excellent medicine distribution directly by using computed tomographic angiography. The 5-year overall survival rate for Stage III patients was 62%, the cause-specific survival rate was 70%, and the local relapse-free survival rate was 89%. Local recurrence, distant metastasis, and occurrences of both were 7%, 38%, and 3%, respectively. The incidence of severe acute hematologic adverse reactions (Grade {>=}3) was 27% for all patients; however, all recovered without interruption of radiotherapy. Severe nonhematologic effects (Grade {>=}3) were 3%, including nausea and ileus. Only 1 patient's radiotherapy was interrupted for a period of 1 week because of ileus. Severe late complication rates (Grade {>=}3) for the bladder, rectum, and intestine were 3%, 3%, and 10%, respectively. Conclusion: A combination of IAIC and systemic chemotherapy should be considered to improve the prognosis of patients with Stage III squamous cell carcinoma of the cervix.

  17. Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma.

    PubMed

    Mizukoshi, Eishiro; Yamashita, Tatsuya; Arai, Kuniaki; Terashima, Takeshi; Kitahara, Masaaki; Nakagawa, Hidetoshi; Iida, Noriho; Fushimi, Kazumi; Kaneko, Shuichi

    2016-06-01

    Hepatic arterial infusion chemotherapy (HAIC) has been employed as an alternative therapy to sorafenib for the patients with advanced hepatocellular carcinoma (HCC). In this study, we performed a comparative analysis of various immune cell responses including tumor-associated antigen (TAA)-specific T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in advanced HCC patients treated with HAIC. Thirty-six HCC patients were examined in the study. Interferon gamma enzyme-linked immunospot assays were performed to examine the frequency of TAA-specific T cells. The frequencies of Tregs and MDSCs were examined by multicolor fluorescence-activated cell sorting analysis. The treatment with HAIC using interferon (IFN)/5-fluorouracil (FU) or IFN/FU + cisplatin modulated the frequencies of various immune cells. In 22.2 % of patients, the frequency of TAA-specific T cells increased after HAIC. Although the frequency of Tregs decreased after HAIC, it was not associated with the prognosis of patients. An analysis of prognostic factors for overall survival identified diameter of the tumor (<3.0 cm), absence of major portal vein invasion, absence of distant metastasis, Union Internationale Contre Le Cancer tumor lymph node metastasis stage (I or II), neutrophil lymphocytic ratio (<2.1) and the frequency of MDSCs (<30.5 %) as factors that prolonged overall survival time after HAIC. Even in the group adjusted with progressive levels of tumors, patients with a low frequency of MDSCs had a significantly longer overall survival time. In conclusion, the frequency of MDSCs before the treatment is a prognostic factor in HAIC against HCC. PMID:27083166

  18. The Fate and Distribution of Autologous Bone Marrow Mesenchymal Stem Cells with Intra-Arterial Infusion in Osteonecrosis of the Femoral Head in Dogs

    PubMed Central

    Jin, Hongting; Xu, Taotao; Chen, Qiqing; Wu, Chengliang; Wang, Pinger; Mao, Qiang; Zhang, Shanxing; Shen, Jiayi; Tong, Peijian

    2016-01-01

    This study aimed to investigate if autologous bone marrow mesenchymal stem cells (MSCs) could treat osteonecrosis of the femoral head (ONFH) and what the fate and distribution of the cells are in dogs. Twelve Beagle dogs were randomly divided into two groups: MSCs group and SHAM operated group. After three weeks, dogs in MSCs group and SHAM operated group were intra-arterially injected with autologous MSCs and 0.9% normal saline, respectively. Eight weeks after treatment, the necrotic volume of the femoral heads was significantly reduced in MSCs group. Moreover, the trabecular bone volume was increased and the empty lacunae rate was decreased in MSCs group. In addition, the BrdU-positive MSCs were unevenly distributed in femoral heads and various vital organs. But no obvious abnormalities were observed. Furthermore, most of BrdU-positive MSCs in necrotic region expressed osteocalcin in MSCs group and a few expressed peroxisome proliferator-activated receptor-γ (PPAR-γ). Taken together, these data indicated that intra-arterially infused MSCs could migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. It suggests that intra-arterial infusion of autologous MSCs might be a feasible and relatively safe method for the treatment of femoral head necrosis. PMID:26779265

  19. Transcatheter intra-arterial infusion of doxorubicin loaded porous magnetic nano-clusters with iodinated oil for the treatment of liver cancer.

    PubMed

    Jeon, Min Jeong; Gordon, Andrew C; Larson, Andrew C; Chung, Jin Wook; Kim, Young Il; Kim, Dong-Hyun

    2016-05-01

    A promising strategy for liver cancer treatment is to deliver chemotherapeutic agents with multifunctional carriers into the tumor tissue via intra-arterial (IA) transcatheter infusion. These carriers should release drugs within the target tissue for prolonged periods and permit intra-procedural multi-modal imaging of selective tumor delivery. This targeted transcatheter delivery approach is enabled via the arterial blood supply to liver tumors and utilized in current clinical practice which is called chemoembolization or radioembolization. During our study, we developed Doxorubicin (Dox) loaded porous magnetic nano-clusters (Dox-pMNCs). The porous structure and carboxylic groups on the MNCs achieved high-drug loading efficiency and sustained drug release, along with magnetic properties resulting in high MRI T2-weighted image contrast. Dox-pMNC within iodinated oil, Dox-pMNCs, and Dox within iodinated oil were infused via hepatic arteries to target liver tumors in a rabbit model. MRI and histological evaluations revealed that the long-term drug release and retention of Dox-pMNCs within iodinated oil induced significantly enhanced liver cancer cell death. PMID:26938029

  20. Development of immunoassays for human urokinase

    NASA Technical Reports Server (NTRS)

    Atassi, M. Zouhair

    1988-01-01

    Radioimmune assays (RIA) and enzyme linked immune assays for measurement of pro-urokinase and the two active forms of the enzyme were developed. Polyclonal and monoclonal antibodies, with desired specificities against preselected synthetic regions of urokinase (UK), were obtained by immunization with the respective synthetic peptides and used to develop RIA for zymogen and the two activated forms of UK.

  1. [A case of non-resectable pancreatic cancer surviving more than 4 years by intra-arterial infusion chemotherapy with angiotensin-II].

    PubMed

    Tsuji, Y; Ohigashi, H; Ishikawa, O; Yasuda, T; Nakano, H; Nakamori, S; Kameyama, M; Hiratsuka, M; Sasaki, Y; Kabuto, T; Furukawa, H; Imaoka, S; Iwanaga, T

    1996-09-01

    This is a report of a 62-year-old woman whose non-resectable pancreatic cancer had been treated effectively by a new method of intra-arterial regional chemotherapy for more than 4 years. A catheter was placed into the celiac artery during laparotomy, and an intra -arterial chemotherapy (methotrexate (50 mg) and Angiotensin-II (AT-II, 5 micrograms)) has been repeated every other week (108 times) in addition to the external beam therapy (50 Gy). Both pain relief and "partial response" in the size of tumor have been obtained, with no hepatic metastasis or adverse effect. She died of brain metastasis at 51 postoperative months. Autopsy revealed that the pancreatic tumor was mostly replaced by fibrous connective tissues. Scintigraphic study indicated that the intra-arterial infusion of AT-II increased the blood flow in the tumor but decreased it in the surrounding non-cancerous tissues. This seemed to explain the effective loco-regional control in the present case. PMID:8854821

  2. Catheterization of the Carotid Artery and Jugular Vein to Perform Hemodynamic Measures, Infusions and Blood Sampling in a Conscious Rat Model

    PubMed Central

    Feng, Jing; Fitz, Yvonne; Li, Yan; Fernandez, Melinda; Cortes Puch, Irene; Wang, Dong; Pazniokas, Stephanie; Bucher, Brandon; Cui, Xizhong; Solomon, Steven B.

    2015-01-01

    The success of a small animal model to study critical illness is, in part, dependent on the ability of the model to simulate the human condition. Intra-tracheal inoculation of a known amount of bacteria has been successfully used to reproduce the pathogenesis of pneumonia which then develops into sepsis. Monitoring hemodynamic parameters and providing standard clinical treatment including infusion of antibiotics, fluids and drugs to maintain blood pressure is critical to simulate routine supportive care in this model but to do so requires both arterial and venous vascular access. The video details the surgical technique for implanting carotid artery and common jugular vein catheters in an anesthetized rat. Following a 72 hr recovery period, the animals will be re-anesthetized and connected to a tether and swivel setup attached to the rodent housing which connects the implanted catheters to the hemodynamic monitoring system. This setup allows free movement of the rat during the study while continuously monitoring pressures, infusing fluids and drugs (antibiotics, vasopressors) and performing blood sampling. PMID:25741606

  3. Disparate Changes in the Mechanical Properties of Murine Carotid Arteries and Aorta in Response to Chronic Infusion of Angiotensin-II

    PubMed Central

    Bersi, M.R.; Collins, M.J.; Wilson, E.; Humphrey, J.D.

    2014-01-01

    Chronic infusion of angiotensin-II has proved useful for generating dissecting aortic aneurysms in atheroprone mice. These lesions preferentially form in the suprarenal abdominal aorta and sometimes in the ascending aorta, but reasons for such localization remain unknown. This study focused on why these lesions do not form in other large (central) arteries. Toward this end, we quantified and compared the geometry, composition, and biaxial material behavior (using a nonlinear constitutive relation) of common carotid arteries from three groups of mice: non-treated controls as well as mice receiving a subcutaneous infusion of angiotensin-II for 28 days that either did or did not lead to the development of a dissecting aortic aneurysm. Consistent with the mild hypertension induced by the angiotensin-II, the carotid wall thickened as expected and remodeled modestly. There was no evidence, however, of a marked loss of elastic fibers or smooth muscle cells, each of which appear to be initiating events for the development of aneurysms, and there was no evidence of intramural discontinuities that might give rise to dissections. PMID:24944461

  4. Hepatic Arterial Infusion Chemotherapy Using Fluorouracil Followed by Systemic Therapy Using Oxaliplatin Plus Fluorouracil and Leucovorin for Patients with Unresectable Liver Metastases from Colorectal Cancer

    SciTech Connect

    Seki, Hiroshi Ozaki, Toshirou; Shiina, Makoto

    2009-07-15

    The purpose of this study was to assess retrospectively the sequential treatment of hepatic arterial infusion (HAI) chemotherapy followed by systemic therapy using oxaliplatin plus 5-flourouracil (5-FU) and leucovorin, namely, FOLFOX, for patients with liver metastases from colorectal cancer. We reviewed 20 patients with unresectable liver metastases from colorectal cancer. Patients were initially treated with HAI chemotherapy until disease progression (5-fluorouracil, 1000 mg/m{sup 2} intra-arterial infusion, weekly) and then with FOLFOX thereafter (FOLFOX4, n = 13; modified FOLFOX6, n = 7). Adverse events, tumor response, and time to progression for each therapy were evaluated retrospectively, and overall survival was estimated. Toxicity of HAI chemotherapy was generally mild. Of 20 patients, adverse events leading to treatment discontinuation occurred in only 1 patient (5%) during initial therapy using HAI chemotherapy, while 9 patients (45%) exhibited adverse events during subsequent FOLFOX therapy. For HAI chemotherapy and FOLFOX, objective response rates were 85.0% and 35.0%, respectively, and median time to progression was 11.6 and 5.1 months, respectively. Median overall survival was 30.1 months. In conclusion, the sequence of HAI chemotherapy followed by FOLFOX is a promising treatment strategy for the long-term use of active chemotherapeutic agents, leading to a superior tumor response and fewer toxic effects in patients with unresectable liver metastases from colorectal cancer.

  5. Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock.

    PubMed

    Nederhoed, Johanna H; Slikkerveer, Jeroen; Meyer, Klaas W; Wisselink, Willem; Musters, René J P; Yeung, Kak K

    2014-03-01

    Acute peripheral arterial thrombosis can be threatening to life and limb. Dissolution of the thrombus local catheter-directed intra-arterial infusion of fibrinolytic agents such as urokinase is the standard therapy for thrombosis; however, this method is time-intensive, and amputation of the affected limb is still needed in 10-30% of cases. Furthermore, thrombolytic therapy carries the risk of bleeding complications. The use of small gas-filled bubbles, or ultrasound contrast agents (UCAs), in combination with ultrasound has been investigated as an improved thrombolytic therapy in acute coronary and cerebral arterial thrombosis. The authors describe a porcine model of acute peripheral arterial occlusion to test contrast-enhanced sonothrombolysis approaches that combine ultrasound, UCAs and fibrinolytic agents and recommend a strategy for preventing severe allergic reactions to UCAs in the pigs. PMID:24552914

  6. Clinical study of urokinase-bound fibrocollagenous tubes.

    PubMed

    Senatore, F; Bernath, F; Meisner, K

    1986-02-01

    Dacron-reinforced fibrocollagenous tubes (FCT) were synthesized from canine mongrels using the mandril-rod technique in order to develop a small diameter (i.e., 4 mm i.d.) vascular graft. They were rendered fibrinolytic by immobilizing urokinase on to the inner surface of the tubes. Urokinase-bound fibrocollagenous tubes (UK-FCT), control FCTs (i.e., no bound enzyme), Perloff grafts (Dr. Perloff, Department of Surgery, University Medical Center, Sidney Australia, has developed a mandril-derived collagenous tube from goats. Samples were implanted for comparative purposes.) and autogeneous saphenous veins, were interposed in the carotid or femoral artery in chronic studies involving 21 canine mongrels. On the basis of Doppler auscultation and palpation, the UK-FCTs were statistically more patent than other candidate prostheses. Fibrin degradation product (FDP) increased in the dogs' systemic circulation with a postoperative peak of 5 days. The host's increase in fibrinolytic activity was shown to be local to the anastamosis. A carotid arterial extracorporeal shunt was designed to evaluate acute patency. Results indicated a rapid thrombosis but no platlet or fibrin adherence to the graft surface was observed, as evidenced by scanning electron microscopy. PMID:2937788

  7. IT infusion

    NASA Technical Reports Server (NTRS)

    Feather, M. S.

    2002-01-01

    Infusing IT technology is a perennial challenge. The Technology Infusion and Maturity Assessment approach of Cornford & Hicks is shown applied to an example of IT infusion: moedl-based V&V of spacecraft software.

  8. Comparison of Fusion Imaging Using a Combined SPECT/CT System and Intra-arterial CT: Assessment of Drug Distribution by an Implantable Port System in Patients Undergoing Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Ikeda, Osamu Kusunoki, Shinichiroh; Nakaura, Takeshi; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Chikamoto, Akira; Kanemitsu, Keiichiro

    2006-06-15

    Hepatic arterial infusion (HAI) chemotherapy is effective for treating primary and metastatic carcinoma of the liver. We compared the perfusion patterns of HAI chemotherapy on intra-arterial port-catheter computed tomography (iapc-CT) and fused images obtained with a combined single-photon emission computed tomography/computed tomography (SPECT/CT) system. We studied 28 patients with primary or metastatic carcinoma of the liver who bore an implantable HAI port system. All underwent abdominal SPECT using Tc-99m-MAA (185 Mbq); the injection rate was 1 mL/min, identical to the chemotherapy infusion rate, and 0.5 mL/sec for iapc-CT. Delivery was through an implantable port. We compared the intrahepatic perfusion (IHP) and extrahepatic perfusion (EHP) patterns of HAI chemotherapy on iapc-CT images and fused images obtained with a combined SPECT/CT system. In 23 of 28 patients (82%), IHP patterns on iapc-CT images and fused images were identical. In 5 of the 28 patients (18%), IHP on fusion images was different from IHP on iapc-CT images. EHP was seen on fused images in 12 of the 28 patients (43%) and on iapc-CT images in 8 patients (29%). In 17 patients (61%), upper gastrointestinal endoscopy revealed gastroduodenal mucosal lesions. EHP was revealed on fused images in 10 of these patients; 9 of them manifested gastroduodenal toxicity at the time of subsequent HAI chemotherapy. Fusion imaging using the combined SPECT/CT system reflects the actual distribution of the infused anticancer agent. This information is valuable not only for monitoring adequate drug distribution but also for avoiding potential extrahepatic complications.

  9. Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma

    SciTech Connect

    Martinez, A.; Goffinet, D.R.; Donaldson, S.S.; Bagshaw, M.A.; Kaplan, H.S.

    1985-01-01

    Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients - of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, the authors believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma.

  10. Phase I/II Study of Sorafenib in Combination with Hepatic Arterial Infusion Chemotherapy Using Low-Dose Cisplatin and 5-Fluorouracil

    PubMed Central

    Ueshima, Kazuomi; Kudo, Masatoshi; Tanaka, Masatoshi; Kumada, Takashi; Chung, Hobyung; Hagiwara, Satoru; Inoue, Tatsuo; Yada, Norihisa; Kitai, Satoshi

    2015-01-01

    We conducted a phase I/II study in patients with advanced hepatocellular carcinoma (HCC) to determine the recommended dose, as well as the safety and efficacy, of combination therapy of sorafenib with hepatic arterial infusion chemotherapy (HAIC) using low dose cisplatin (CDDP) and 5-fluorouracil (5FU). Cohorts consisting of 3-6 patients with HCC received an escalated dose of CDDP and 5-FU until a maximum-tolerated dose was achieved. The treatment regimen was as follows: oral administration of sorafenib (400 mg twice daily for 28 days) combined with HAIC using CDDP (14-20 mg/m2, on days 1 and 8) and 5-FU (170-330 mg/m2, continuously on days 1-5 and 8-12) via an implanted catheter system). Each treatment cycle consisted of 28 days and three cycles of combination therapy. At the end of the first cycle, adverse events were evaluated and future dose escalation was determined. Eighteen patients with advanced HCC were enrolled. Dose-limiting toxicity was observed in two patients from cohort 1 (erythema multiforme and grade 4 thrombocytopenia) and in one patient from cohort 2 (erythema multiforme). Seven of the 18 patients achieved a partial response, seven showed stable disease, two were diagnosed as progressive disease, and two were not assessable. The response rate was 38.9% and the disease control rate was 77.8%. The time-to-progression was 9.7 months and the 1-year survival rate was 88.2%. Oral administration of 400 mg of sorafenib twice daily, 20 mg/m2 of intra-arterial infusion of CDDP, and 5-FU at 330 mg/m2 are the recommended doses for combination therapy, which was well tolerated and efficacious. This combination therapy may be a promising treatment for patients with advanced HCC. A large prospective randomized multicenter study (ClinicalTrials.gov Identifier NCT01214343) is ongoing. PMID:26734580

  11. Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study

    PubMed Central

    2010-01-01

    Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE) in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP), central venous pressure (CVP), systemic vascular resistance (SVR), ejection fracture (EF), heart rate (HR), mean pulmonary artery pressure (MPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20%) in group A and B respectively (p = 0,042). Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF were recorded in

  12. Perioperative infusion of low- dose of vasopressin for prevention and management of vasodilatory vasoplegic syndrome in patients undergoing coronary artery bypass grafting-A double-blind randomized study.

    PubMed

    Papadopoulos, Georgios; Sintou, Eleni; Siminelakis, Stavros; Koletsis, Efstratios; Baikoussis, Nikolaos G; Apostolakis, Efstratios

    2010-01-01

    Preoperative medication by inhibitors of angiotensin-converting enzyme (ACE) in coronary artery patients predisposes to vasoplegic shock early after coronary artery bypass grafting. Although in the majority of the cases this shock is mild, in some of them it appears as a situation, "intractable" to high-catecholamine dose medication. In this study we examined the possible role of prophylactic infusion of low-dose vasopressin, during and for the four hours post-bypass after cardiopulmonary bypass, in an effort to prevent this syndrome. In addition, we studied the influence of infused vasopressin on the hemodynamics of the patients, as well as on the postoperative urine-output and blood-loss. In our study 50 patients undergoing coronary artery bypass grafting were included in a blind-randomized basis. Two main criteria were used for the eligibility of patients for coronary artery bypass grafting: ejection fraction between 30-40%, and patients receiving ACE inhibitors, at least for four weeks preoperatively. The patients were randomly divided in two groups, the group A who were infused with 0.03 IU/min vasopressin and the group B who were infused with normal saline intraoperativelly and for the 4 postoperative hours. Measurements of mean artery pressure (MAP), central venous pressure (CVP), systemic vascular resistance (SVR), ejection fracture (EF), heart rate (HR), mean pulmonary artery pressure (MPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were performed before, during, and after the operation. The requirements of catecholamine support, the urine-output, the blood-loss, and the requirements in blood, plasma and platelets for the first 24 hours were included in the data collected. The incidence of vasodilatory shock was significantly lower (8% vs 20%) in group A and B respectively (p = 0,042). Generally, the mortality was 12%, exclusively deriving from group B. Postoperatively, significant higher values of MAP, CVP, SVR and EF were recorded in

  13. Clinical Application of a New Indwelling Catheter with a Side-Hole and Spirally Arranged Shape-Memory Alloy for Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Yagihashi, Kunihiro Takizawa, Kenji; Ogawa, Yukihisa; Okamoto, Kyoko; Yoshimatsu, Misako; Fujikawa, Atsuko; Shimamoto, Hiroshi; Nakajima, Yasuo

    2010-12-15

    A new indwelling catheter, G-spiral (GSP), was developed for hepatic arterial infusion chemotherapy (HAIC) by way of an implanted catheter-port system (CPS). Here we evaluated its physical properties and the outcomes of its clinical use. The GSP vessel-fixing power and its ability to follow a guidewire were determined with a vascular in vitro model, and Student t test was used to determine statistical significance (P < 0.05). A retrospective analysis was performed to evaluate the technical success rate and to identify the clinical complications associated with radiologic CPS implantation with GSP in 65 patients with unresectable hepatic tumors. The mean vessel-fixing power of the GSP (14.4 g) significantly differed from that of a GSP with a cut shape-memory alloy (3.3 g). The mean resistance to following the guidewire displayed by the GSP (88.5 g) was significantly less than that for a 5F W-spiral (106.3 g) or 4F Cobra-type angiographic catheter (117.8 g). The CPS was placed successfully in 64 of 65 cases (98.5%). Hepatic artery occlusion was observed in one case. Occlusion, cracking, and infection of CPS were observed in one, two, and one case, respectively. The GSP is a highly useful indwelling catheter that can be used for HAIC.

  14. Treatment of hepatocellular carcinoma (HCC) by intra-arterial infusion of radio-emitter compounds: trans-arterial radio-embolisation of HCC.

    PubMed

    Andreana, Lorenzo; Isgrò, Graziella; Marelli, Laura; Davies, Neil; Yu, Dominic; Navalkissoor, Shaunak; Burroughs, Andrew K

    2012-10-01

    Traditional radiotherapy is only effective in treating hepatocellular cancer (HCC) in doses above 50 Gy, but this is above the recommended liver radiation exposure of about 35 Gy, which is an important limitation making this treatment unsuitable for routine clinical practice. Trans-arterial radio-embolisation (TARE), consists of delivery of compounds linked to radio-emitter particles which end up in hepatic end-arterioles or show affinity for the neoplasm itself, allowing localised delivery of doses beyond 120 Gy. These are well tolerated in patients treated with this type of internal radiation therapy. TARE for HCC is used for palliative treatment of advanced disease which cannot be treated in other ways, or for tumour down-staging before liver transplantation, or as adjuvant therapy for surgically resected HCC. Tumour response after TARE is between 25% and 60% if assessed by using RECIST criteria, and 80% by EASL criteria. In this review we outline the advantages and limitations of radio-emitter therapy including 131-I, 90-Y and 188-Re. We include several observational, and all comparative studies using these compounds. In particular we compare TARE to trans-arterial chemo-embolisation and other intra-arterial techniques. PMID:22169503

  15. Infusion Extractor

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R.

    1988-01-01

    Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

  16. Combined Arterial Infusion and Stent Implantation Compared with Metal Stent Alone in Treatment of Malignant Gastroduodenal Obstruction

    SciTech Connect

    Wang Zhongmin; Chen Kemin; Gong Ju; Zheng Yunfeng; Wang Tianxiang

    2009-09-15

    Many patients with malignant gastroduodenal obstruction have an unresectable primary lesion and distant metastases, which may prompt palliative management to allow the patient to eat and to improve the quality of life. Intraluminal metallic stent implantation (MSI) under fluoroscopic guidance has been reported to be an effective option for symptomatic relief in these patients, with a good safety record. An alternative, dual interventional therapy (DIT), has been used during the last decade, in which prosthesis insertion is followed by intra-arterial chemotherapy via the tumor-feeding arteries. The aim of this study was to compare success rates, complication rates, and survival time between MSI and DIT in patients who presented with gastroduodenal obstruction from advanced upper gastrointestinal tract cancer. All consecutive patients with malignant gastroduodenal obstruction seen at our center between October 2002 and August 2007 were retrospectively studied. Patients were treated palliatively by either MSI or DIT by the patient's or the next of kin's decision. Outcomes included technical and clinical success, complication rates, and survival. Of the 164 patients with malignant gastric and duodenal outlet obstructions, 80 (49%) underwent stent insertion as the primary therapy, while the remaining 84 (51%) received DIT. Clinical characteristics were similar between the two groups. In the MSI cohort initial stent implantation was successful in 73 patients (91%), two stents were used in 5 patients, and delayed additional stent insertion for stent obstruction related to tumor overgrowth was required in 3 patients during follow-up. In the DIT cohort the technical success rate was 94%, 3 patients required two stents, and stent obstruction occurred in 2 patients after initial stent placement. Early postprocedural clinical success, indicated by average dysphagia score, improved significantly in both groups: MSI group, from 4.56 to 1.51 (P < 0.01); and DIT group, from 4

  17. [Cases of advanced cholangiocarcinoma showing partial response by the combination chemotherapy including protracted continuous infusion of 5-FU combined with intravenous administration of low-dose leucovorin and intra-arterial administration of MMC and CQ].

    PubMed

    Tsushima, K; Sakata, Y; Shiratori, Y; Sakamoto, J; Koeda, J; Yamada, Y; Soma, N; Tamura, K; Yoshiwara, A; Soma, Y

    1991-12-01

    We treated a patient with advanced cholangiocarcinoma with a new combination chemotherapy (modified MQF). The regimen consisted of intra-arterial administration of MMC (20 mg/body) and CQ (4 mg/body), protracted continuous infusion of 5-FU (500 mg/body) and intravenous administration of low-dose leucovorin (30 mg/body). More than 50% reduction in the liver tumor for over 4 weeks was obtained by the therapy. As for toxicity, diarrhea and stomatitis were observed. PMID:1660702

  18. Randomized Phase II Study of 5-Fluorouracil Hepatic Arterial Infusion with or without Antineoplastons as an Adjuvant Therapy after Hepatectomy for Liver Metastases from Colorectal Cancer

    PubMed Central

    Ogata, Yutaka; Matono, Keiko; Tsuda, Hideaki; Ushijima, Masataka; Uchida, Shinji; Akagi, Yoshito; Shirouzu, Kazuo

    2015-01-01

    Background Antineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10), phenylacetylglutamine plus phenylacetylisoglutamine (A10-I), and phenylacetylglutamine plus phenylacetate (AS2-1). This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver. Methods Sixty-five patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998- 2004 in Kurume University Hospital. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1) plus HAI (AN arm) or HAI alone (control arm) based on the number of metastases and presence/ absence of extra-hepatic metastasis at the time of surgery. Primary endpoint was cancer-specific survival (CSS); secondary endpoints were relapse-free survival (RFS), status and extent of recurrence, salvage surgery (rate) and toxicity. Findings Overall survival was not statistically improved (p=0.105) in the AN arm (n=32). RFS was not significant (p=0.343). Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n=33) with a median survival time 67 months (95%CI 43-not calculated) versus 39 months (95%CI 28-47) (p=0.037) and 5 year CSS rate 60% versus 32% respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumours in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the

  19. Infusion extractor

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R. (Inventor)

    1986-01-01

    This invention relates to an apparatus and method of removing desirable constituents from an infusible material by infusion extraction. A piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber. The method is applicable to operation in low or micro-gravity environments.

  20. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Impact of Early Response to 4 Weeks of Treatment

    PubMed Central

    Lin, Chen-Chun; Hung, Chien-Fu; Chen, Wei-Ting; Lin, Shi-Ming

    2015-01-01

    Aim The aim of the study was to investigate the impact of early response (ER) to hepatic arterial infusion chemotherapy (HAIC) on outcomes of patients with advanced hepatocellular carcinoma (HCC) complicated with major portal vein tumor thrombosis (PVTT). Methods Thirty-nine patients receiving HAIC with low-dose cisplatin, 5-fluorouracil (5FU), and leucovorin were enrolled. One course of HAIC consisted of 5 days of treatment and 2 days rest per week for 4 consecutive weeks. ER was categorized as complete response, partial response, or minor response and was determined by World Health Organization criteria with dynamic computed tomography findings performed within 1 week after the first course of HAIC. Results Thirteen (33%) patients achieved an ER. Twelve (92.3%) of these 13 ER patients achieved a higher overall response than all but one (3.8%) of the 26 non-early responders (NERs) (p<0.001). ER was the exclusive independent favorable factor for survival (p=0.003). Downstaging of tumors was noted in 76.9% of ERs, and these patients could proceed to locoregional therapies. ER patients subsequently had a higher 1-year survival (76.9% vs. 3.8%, p<0.001) and 6-month progression-free survival (PFS) (84.6% vs. 15.4%, p<0.001) than those for NERs. Only 8% of patients experienced grade 3 or higher toxicity during the first 4-week course of HAIC. Conclusions HAIC can yield a satisfactory ER for advanced HCC with PVTT. Moreover, achievement of ER after HAIC in advanced HCC with PVTT is strongly associated with better overall survival and PFS. PMID:26734578

  1. Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method

    PubMed Central

    Fukubayashi, Kotaro; Tanaka, Motohiko; Izumi, Kazuhiro; Watanabe, Takehisa; Fujie, Satomi; Kawasaki, Takeshi; Yoshimaru, Yoko; Tateyama, Masakuni; Setoyama, Hiroko; Naoe, Hideaki; Kikuchi, Ken; Sasaki, Yutaka

    2015-01-01

    While sorafenib (SFN) is the established worldwide standard therapeutic agent for advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) is also considered a favorable treatment for some advanced HCCs. This study aimed to evaluate each treatment and provide an optimal therapeutic choice for advanced HCCs. We analyzed 72 patients treated with SFN and 128 patients receiving HAIC. Both treatment groups were analyzed for prognostic and disease progression factors, and matched pair analysis was performed using the propensity score matching method. The preferable status of intrahepatic lesions, that is, no lesions or only a single (<3 cm) intrahepetic lesion, was positively associated with good prognosis and negatively associated with disease progression in the SFN group. Maximum tumor size (>5 cm) and low albumin (≤3.4 g/dL) were poor prognostic and disease progression factors in the HAIC group. Analysis of 53 patients selected from each of the SFN and HAIC groups based on the propensity score matching method showed no significant differences in survival or disease progression between the two matched subgroups. On the other hand, progression-free survival (PFS) in the HAIC-matched subgroup was significantly longer than in the SFN-matched subgroup, particularly in patients with portal vein invasion (PVI) and/or without extrahepatic spread (EHS). The treatment efficacy of HAIC is similar to that of SFN regarding survival and disease progression. Longer PFS might be expected for HAIC compared with SFN, particularly in patients with PVI and/or without EHS. PMID:26044168

  2. Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver

    PubMed Central

    Said, Rabih; Kurzrock, Razelle; Naing, Aung; Hong, David S.; Fu, Siqing; Piha-Paul, Sarina; Wheler, Jennifer J; Janku, Filip; Kee, Bryan K; Bidyasar, Savita; Lim, Joann; Wallace, Michael; Tsimberidou, Apostolia M.

    2015-01-01

    BACKGROUND Liver metastases are associated with a poor prognosis. We investigated the use of hepatic arterial infusion (HAI) of irinotecan combination therapy in patients with liver metastases. PATIENTS AND METHODS Patients with histologically confirmed advanced cancer with liver metastases that was refractory to standard therapy were eligible. A standard “3+3” phase I study design was used to determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Three cohorts were evaluated: HAI of irinotecan with systemic intravenous (IV) (a) bevacizumab, (b) oxaliplatin and bevacizumab, or (c) bevacizumab and cetuximab. RESULTS From October 2009 through December 2013, 98 patients with various tumor types were enrolled (median age, 62 years, range, 34–85; and median number of prior therapies, 4, range, 1–11). In cohorts A and C, dose escalation continued until the highest dose level—considered the MTD—was reached. In cohort B, dose escalation continued until dose level 3, and dose level 2 was considered the MTD. Rates of grade 3/4 adverse events were as follows: diarrhea, 8%; fatigue, 4%; neutropenia, 4%; thrombocytopenia, 2%; and skin rash, 2%. Seventy-seven patients were evaluable for response. Partial response was noted in 5 (6.5%) patients (neuroendocrine cancer, n=2; CRC, n=2; NSCLC, n=1); and stable disease ≥ 6 months in 17 (22.1%) patients (CRC, n=13; breast, n=1; neuroendocrine, n=1; NSCLC, n=1; pancreatic, n=1). CONCLUSIONS HAI irinotecan in combination with bevacizumab; oxaliplatin plus bevacizumab; or cetuximab plus bevacizumab was safe and may be a treatment option for selected patients with advanced cancer and liver involvement. PMID:25990659

  3. Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement

    PubMed Central

    Moulder, Stacy; Fu, Siqing; Wen, Sijin; Naing, Aung; Bedikian, Agop Y.; Daring, Shawn; Uehara, Cynthia; Ng, Chaan; Wallace, Michael; Camacho, Luis; Kurzrock, Razelle

    2011-01-01

    Purpose We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement. Methods Patients were treated with HAI cisplatin 100–125 mg/m2 (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20–35 mg/m2 IV (day 1) every 28 days. A “3 + 3” study design was used. Results Thirty patients were treated (median age, 56 years). Diagnoses were breast cancer (n = 11), colorectal cancer (n = 8), ocular melanoma (n = 4), and other (n = 7). The median number of prior therapies was 5. The maximum tolerated dose (MTD) was at the 100/35 mg/m2 level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m2 and systemic doxil 35 mg/m2 dose level. The most common toxicities were nausea/vomiting and fatigue. Of 24 patients evaluable for response, 4 (17%) had a partial response (PR) and 7 (29%) had stable disease (SD) for ≥4 months. Of the 11 patients with breast cancer, 3 (27%) had a PR and 5 (45%) had SD for ≥4 months. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD for 4 months. One patient with hepatocellular carcinoma had SD for 4 months. Of 12 evaluable patients treated at the MTD, 2 (17%) had a PR and 5 (42%) had SD. Conclusion The MTD was HAI cisplatin 100 mg/m2 and systemic doxil 35 mg/m2. This regimen demonstrated anti-tumor activity, especially in breast cancer. PMID:20204368

  4. Quantitative method of measuring cancer cell urokinase and metastatic potential

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R. (Inventor)

    1993-01-01

    The metastatic potential of tumors can be evaluated by the quantitative detection of urokinase and DNA. The cell sample selected for examination is analyzed for the presence of high levels of urokinase and abnormal DNA using analytical flow cytometry and digital image analysis. Other factors such as membrane associated urokinase, increased DNA synthesis rates and certain receptors can be used in the method for detection of potentially invasive tumors.

  5. Fiberoptic study on the effects of transluminal angioplasty in experimental occlusive arterial thrombosis.

    PubMed

    Tomaru, T; Uchida, Y; Sugimoto, T

    1988-02-01

    Percutaneous transluminal coronary angioplasty has been proposed as definitive therapy for coronary recanalization of occluded coronary arteries in patients with acute myocardial infarction (AMI). The effects of transluminal angioplasty (TA) on experimental occlusive canine arterial thrombi that closely simulated the clinical condition was examined by a fiberoptic method. Experimental arterial thrombosis was produced by endothelial denudation and induction of luminal stenosis. Eighteen dogs that showed total occlusion of the iliac artery with thrombi were evaluated. Seven dogs (group A) with 6-hour-old thrombi received 20,000 IU/kg intravenous urokinase (UK) but did not show recanalization. TA was performed with a Gruentzig or Simpson-Robert balloon catheter and its effect was evaluated by a vascular fibroscope. Eight dogs (group B) with 6-hour-old thrombi underwent primary TA. After TA, less than 50% luminal obstruction with residual thrombi was visualized in five dogs (71%) of group A and four dogs (50%) of group B. Residual thrombi showed a doughnut-like or globular type shape and consisted of dense fibrin networks and compact platelet aggregates. All dogs in group B received 20,000 IU/kg intravenous UK after TA, but most of them showed progression of thrombus size despite UK infusion. In conclusion, the results suggest (1) that TA is effective in recanalization of an occluded artery with aged thrombus that is resistant to thrombolytic therapy and (2) that vascular fiberscope is a useful method for evaluation of the effects of TA on occlusive arterial thrombus. PMID:2963513

  6. Antibodies Against Three Forms of Urokinase

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.; Atassi, M. Zouhair

    2007-01-01

    Antibodies that bind to preselected regions of the urokinase molecule have been developed. These antibodies can be used to measure small quantities of each of three molecular forms of urokinase that could be contained in microsamples or conditioned media harvested from cultures of mammalian cells. Previously available antibodies and assay techniques do not yield both clear distinctions among, and measurements of, all three forms. Urokinase is a zymogen that is synthesized in a single-chain form, called ScuPA, which is composed of 411 amino acid residues (see figure). ScuPA has very little enzyme activity, but it can be activated in two ways: (1) by cleavage of the peptide bond lysine 158/isoleucine 159 and the loss of lysine 158 to obtain the high molecular-weight (HMW) form of the enzyme or (2) by cleavage of the bond lysine 135/lysine 136 to obtain the low-molecular-weight (LMW) form of the enzyme. The antibodies in question were produced in mice and rabbits by use of peptides as immunogens. The peptides were selected to obtain antibodies that bind to regions of ScuPA that include the lysine 158/isoleucine 159 and the lysine 135/lysine 136 bonds. The antibodies include monoclonal and polyclonal ones that yield indications as to whether either of these bonds is intact. The polyclonal antibodies include ones that preferentially bind to the HMW or LMW forms of the urokinase molecule. The monoclonal antibodies include ones that discriminate between the ScuPA and the HMW form. A combination of these molecular-specific antibodies will enable simultaneous assays of the ScuPA, HMW, and LMW forms in the same specimen of culture medium.

  7. Urokinase perfusion prevents intrahepatic ischemic-type biliary lesion in donor livers

    PubMed Central

    Lang, Ren; He, Qiang; Jin, Zhong-Kui; Han, Dong-Dong; Chen, Da-Zhi

    2009-01-01

    AIM: To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions (IITBLs). METHODS: A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions. The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year. The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year. In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver. The incidence of IITBLs was compared between the two groups. RESULTS: In the control group, the incidence of IITBLs was 5.9% (13/220 cases) after 3-11 mo of transplantation. In the experimental group, two recipients (1.4%) developed IITBLs at 3 and 6 mo after transplantation, respectively. The difference in the incidence between the two groups was statistically significant (P < 0.05). CONCLUSION: Double perfusion of cadaveric livers from non-heart-beating donors with urokinase may reduce the incidence of IITBLs. PMID:19630111

  8. Increased Plasminogen Activator (Urokinase) in Tissue Culture After Fibrin Deposition

    PubMed Central

    Bernik, Maria B.

    1973-01-01

    Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways—affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis. PMID:4266421

  9. Flushing the liver with urokinase before transplantation does not prevent nonanastomotic biliary strictures.

    PubMed

    Pietersen, Lars C; den Dulk, A Claire; Braat, Andries E; Putter, Hein; Korkmaz, Kerem Sebib; Baranski, Andre G; Schaapherder, Alexander F M; Dubbeld, Jeroen; van Hoek, Bart; Ringers, Jan

    2016-04-01

    The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re-)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End-Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty-three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group (P = 0.68). Analyzed separately for donation after circulatory death (P = 0.42) or donation after brain death (P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups (P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group (P < 0.001). This study has its limitations by its retrospective character. A multi-institutional prospective study could clarify this issue. In conclusion, arterial flushing of the liver with urokinase immediately before implantation did not lead to a lower incidence of NAS in this study, nor did it lead to increased blood loss. Liver Transplantation 22 420-426 2016 AASLD. PMID:26600096

  10. Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood-brain barrier opening after intra-arterial infusion.

    PubMed

    Song, Xiaolei; Walczak, Piotr; He, Xiaowei; Yang, Xing; Pearl, Monica; Bulte, Jeff Wm; Pomper, Martin G; McMahon, Michael T; Janowski, Mirosław

    2016-07-01

    The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. Predicted, focal opening of the BBB through intra-arterial infusion of hyperosmolar mannitol is feasible, but there is a need to facilitate imaging techniques (e.g. MRI) to guide interventional procedures and assess the outcomes. Here, we show that salicylic acid analogues (SAA) can depict the brain territory supplied by the catheter and detect the BBB opening, through chemical exchange saturation transfer (CEST) MRI. Hyperosmolar SAA solutions themselves are also capable of opening the BBB, and, when multiple SAA agents were co-injected, their locoregional perfusion could be differentiated. PMID:26980755

  11. [Combination Chemotherapy Using Sorafenib and Hepatic Arterial Infusion with a Fine-Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis--A Case Report].

    PubMed

    Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Murata, Akihiro; Sakae, Masayuki; Kurihara, Shigeaki; Tashima, Tetsuzo; Deguchi, Sota; Nakai, Takashi; Kawasaki, Yasuko; Kioka, Kiyohide

    2015-11-01

    Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor-shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call®). A 57-year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call® was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call® has been performed once for 6 weeks. After performing HAIC with IA-call® 5 times, the serum levels of HCC tumor markers AFP and PIVKA-Ⅱdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease. PMID:26805203

  12. Investigation of long chain omega-3 PUFAs on arterial blood pressure, vascular reactivity and survival in angiotensin II-infused Apolipoprotein E-knockout mice.

    PubMed

    Bürgin-Maunder, Corinna S; Nataatmadja, Maria; Vella, Rebecca K; Fenning, Andrew S; Brooks, Peter R; Russell, Fraser D

    2016-02-01

    Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) decrease inflammation and oxidative stress in an angiotensin II-infused apolipoprotein E-knockout (ApoE(-/-)) mouse model of AAA. This study investigated the effects of LC n-3 PUFAs on blood pressure and vascular reactivity in fourteen angiotensin II-infused ApoE(-/-) male mice. Blood pressure was obtained using a non-invasive tail cuff method and whole blood was collected by cardiac puncture. Vascular reactivity of the thoracic aorta was assessed using wire myography and activation of endothelial nitric oxide synthase (eNOS) was determined by immunohistochemistry. A high LC n-3 PUFA diet increased the omega-3 index and reduced the n-6 to n-3 PUFA ratio. At day 10 post-infusion with angiotensin II, there was no difference in systolic blood pressure or diastolic blood pressure in mice fed the high or low n-3 PUFA diets. The high LC n-3 PUFA diet resulted in a non-significant trend for delay in time to death from abdominal aortic rupture. Vascular reactivity and eNOS activation remained unchanged in mice fed the high compared to the low LC n-3 PUFA diet. This study argues against direct improvement in vascular reactivity in ApoE(-/-) mice that were supplemented with n-3 PUFA for 8 weeks prior to infusion with angiotensin II. PMID:26638987

  13. Intraosseous infusion.

    PubMed

    LaRocco, Brian G; Wang, Henry E

    2003-01-01

    Establishing vascular access is vital in the resuscitation of critically-ill children and adults. Intraosseous infusion (IOI) is a viable route for providing vascular access when traditional intravenous methods cannot be accomplished. IOI is relatively easy to perform and is a standard recommended intervention for the resuscitation of both adults and children. The authors review the history, anatomy, technique, and clinical application of IOI. They also highlight the use of IOI in the prehospital setting. PMID:12710793

  14. [Effectiveness of systemic chemotherapy of GEM+CBDCA+5-FU/LV and hepatic arterial infusion of CDDP in a case of advanced, combined hepatocellular-cholangiocarcinoma with multiple lung metastases].

    PubMed

    Tani, Satoshi; Murata, Shigemasa; Tamura, Miho; Fukunaga, Kaoru; Morita, Munetaka; Hirata, Yuzo; Iida, Hiroya; Kakuno, Ayako; Nishigami, Takashi; Yamanaka, Naoki

    2011-11-01

    This patient is a male in his 30's. He was diagnosed as hepatitis B virus-related huge primary liver cancer, 10cm in diameter, located in segment 4, accompanied with left portal thrombus and multiple lung metastases. Ten months after repeating systemic chemotherapy using gemcitabine (GEM)+carboplatin (CBDCA)+5-FU/leucovorin (LV) and hepatic arterial infusion chemotherapy with cisplatin (CDDP) 4 times, extended left lobectomy with caudate lobe could be successfully performed because of marked reducion of the huge tumor. The pathology revealed almost entirely necrotic changes of the main tumor, and the remaining, viable tumor nests showed combined hepatocellular and cholangiocarcinoma. Systemic chemotherapy was repeatedly given afterwards, which kept the pulmonary metastases stable without growth. The present case suggests that systemic chemotherapy using GEM+CBDCA+5-FU/LV may be useful in the multimodal treatment for the combined hepatocellular and cholangiocarcinoma with distant metastases. PMID:22056711

  15. Interaction of urokinase A chain with the receptor of human keratinocytes stimulates release of urokinase-like plasminogen activator

    SciTech Connect

    Fibbi, G.; Magnelli, L.; Pucci, M.; Del Rosso, M. )

    1990-03-01

    On the basis of a fibrinolytic assay with {sup 125}I-fibrin, zymography, and immunoprobing with anti-human urokinase antibody, the authors have observed that the in vitro established NCTC human keratinocyte cell line releases into the culture medium a 54,000-Da plasminogen activator which is indistinguishable from human urokinase. Only the early release following the washing of keratinocyte monolayers is accounted for by secretion of preformed enzyme, while late secretory events require the de novo synthesis of urokinase. The released enzyme can interact by autocriny with its own receptor present on keratinocytes. The addition to the keratinocyte culture medium of the urokinase A chain can stimulate a concentration-dependent urokinase oversecretion, which is not paralleled by oversecretion of plasminogen activator inhibitor-1. Since stimulation of urokinase production can be obtained by an A chain concentration which was previously shown to be efficient in inducing keratinocyte mobilization in an in vitro migration model system, they hypothesize that this mechanism may be important in vivo during the process of wound repair.

  16. Congenital giant cardiac tumor with severe left-ventricular inflow and outflow obstruction and arrhythmia treated with pulmonary artery banding and long-term amiodarone infusion

    PubMed Central

    Takeuchi, Daiji; Hiramatsu, Takeshi; Nakanishi, Toshio

    2012-01-01

    We report a congenital giant cardiac tumor that occupied the majority of left ventricular cavity with severe left ventricular inflow and outflow obstruction. The hemodynamics were similar to univentricular physiology. He was treated with prostaglandins and bilateral pulmonary artery banding. He had frequent supraventricular tachycardia associated with ventricular pre-excitation that was controlled by long-term administration of intravenous amiodarone. The patient died due to sepsis after 3 months. PMID:22529609

  17. A single infusion of MDCO-216 (ApoA-1 Milano/POPC) increases ABCA1-mediated cholesterol efflux and pre-beta 1 HDL in healthy volunteers and patients with stable coronary artery disease

    PubMed Central

    Kallend, D.G.; Reijers, J.A.A.; Bellibas, S.E.; Bobillier, A.; Kempen, H.; Burggraaf, J.; Moerland, M.; Wijngaard, P.L.J.

    2016-01-01

    Aims Apolipoprotein A-1 (ApoA-1), based on epidemiology, is inversely associated with cardiovascular (CV) events. Human carriers of the ApoA-1 Milano variant have a reduced incidence of CV disease. Regression of atherosclerotic plaque burden was previously observed on intravascular ultrasound (IVUS) with ETC-216, a predecessor of MDCO-216. MDCO-216, a complex of dimeric ApoA-1 Milano and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, is being developed to reduce atherosclerotic plaque burden and CV events. We investigated the efficacy and safety of a single infusion of MDCO-216 in healthy volunteers and in patients with coronary artery disease (CAD). Methods and results Twenty-four healthy volunteers and 24 patients with documented CAD received a 2-h infusion of MDCO-216 in a randomized, placebo controlled, single ascending dose study. Five cohorts of healthy volunteers and four cohorts of CAD patients received ApoA-1 Milano doses ranging from 5 to 40 mg/kg. Subjects were followed for 30 days. Dose-dependent increases in ApoA-1, phospholipid, and pre-beta 1 HDL and decreases in ApoE were observed. Prominent and sustained increases in triglyceride, and decreases in HDL-C, endogenous ApoA-1 and ApoA-II occurred at doses >20 mg/kg and profound increases in ABCA1-mediated cholesterol efflux were observed. Other lipid and lipoprotein parameters were generally unchanged. MDCO-216 was well tolerated. Conclusions MDCO-216-modulated lipid parameters profoundly increased ABCA1-mediated cholesterol efflux and was well tolerated. These single-dose data support further development of this agent for reducing atherosclerotic disease and subsequent CV events. PMID:27418968

  18. Fluorescent-Antibody Measurement Of Cancer-Cell Urokinase

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.

    1993-01-01

    Combination of laboratory techniques provides measurements of amounts of urokinase in and between normal and cancer cells. Includes use of fluorescent antibodies specific against different forms of urokinase-type plasminogen activator, (uPA), fluorescence microscopy, quantitative analysis of images of sections of tumor tissue, and flow cytometry of different uPA's and deoxyribonucleic acid (DNA) found in suspended-tumor-cell preparations. Measurements provide statistical method for indicating or predicting metastatic potentials of some invasive tumors. Assessments of metastatic potentials based on such measurements used in determining appropriate follow-up procedures after surgical removal of tumors.

  19. Urokinase-controlled tumor penetrating peptide.

    PubMed

    Braun, Gary B; Sugahara, Kazuki N; Yu, Olivia M; Kotamraju, Venkata Ramana; Mölder, Tarmo; Lowy, Andrew M; Ruoslahti, Erkki; Teesalu, Tambet

    2016-06-28

    Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of tumor penetrating peptides identified using phage display are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA). We expressed the peptide, uCendR (RPARSGR↓SAGGSVA, ↓ shows cleavage site), on phage or coated it onto silver nanoparticles and showed that it is cleaved by uPA, and that the cleavage triggers binding to recombinant NRP-1 and to NPR-1-expressing cells. Upon systemic administration to mice bearing uPA-overexpressing breast tumors, FAM-labeled uCendR peptide and uCendR-coated nanoparticles preferentially accumulated in tumor tissue. We also show that uCendR phage internalization into cultured cancer cells and its penetration in explants of murine tumors and clinical tumor explants can be potentiated by combining the uCendR peptide with tumor-homing module, CRGDC. Our work demonstrates the feasibility of designing tumor-penetrating peptides that are activated by a specific tumor protease. As upregulation of protease expression is one of the hallmarks of cancer, and numerous tumor proteases have substrate specificities compatible with proteolytic unmasking of cryptic CendR motifs, the strategy described here may provide a generic approach for designing proteolytically-actuated peptides for tumor-penetrative payload delivery. PMID:27106816

  20. Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrins.

    PubMed

    Tang, Chi-Hui; Hill, Marla L; Brumwell, Alexis N; Chapman, Harold A; Wei, Ying

    2008-11-15

    The urokinase receptor (uPAR) is upregulated upon tumor cell invasion and correlates with poor lung cancer survival. Although a cis-interaction with integrins has been ascribed to uPAR, whether this interaction alone is critical to urokinase (uPA)- and uPAR-dependent signaling and tumor promotion is unclear. Here we report the functional consequences of point mutations of uPAR (H249A-D262A) that eliminate beta1 integrin interactions but maintain uPA binding, vitronectin attachment and association with alphaV integrins, caveolin and epidermal growth factor receptor. Disruption of uPAR interactions with beta1 integrins recapitulated previously reported findings with beta1-integrin-derived peptides that attenuated matrix-dependent ERK activation, MMP expression and in vitro migration by human lung adenocarcinoma cell lines. The uPAR mutant cells acquired enhanced capacity to adhere to vitronectin via uPAR-alphaVbeta5-integrin, rather than through the uPAR-alpha3beta1-integrin complex and they were unable to initiate uPA signaling to activate ERK, Akt or Stat1. In an orthotopic lung cancer model, uPAR mutant cells exhibited reduced tumor size compared with cells expressing wild-type uPAR. Taken together, the results indicate that uPAR-beta1-integrin interactions are essential to signals induced by integrin matrix ligands or uPA that support lung cancer cell invasion in vitro and progression in vivo. PMID:18940913

  1. A Case Report of Long-Term Survival following Hepatic Arterial Infusion of L-Folinic Acid Modulated 5-Fluorouracil Combined with Intravenous Irinotecan and Cetuximab Followed by Hepatectomy in a Patient with Initially Unresectable Colorectal Liver Metastases

    PubMed Central

    Van Bael, Kobe; Jansen, Yanina; Seremet, Teofila; Engels, Benedikt; Delvaux, Georges

    2015-01-01

    A 43-year-old women admitted to our hospital for weight loss, anorexia, and abdominal pain was diagnosed with sigmoid neoplasm and multiple bilobar liver metastases. This patient received six cycles of systemic FOLFOX prior to a laparoscopically assisted anterior resection of the rectosigmoid for a poorly differentiated invasive adenocarcinoma T2N2M1, K-RAS negative (wild type). Hepatic arterial infusion (HAI) of L-folinic acid modulated 5-fluorouracil (LV/5-FU) with intravenous (iv) irinotecan (FOLFIRI) and cetuximab as adjuvant therapy resulted in a complete metabolic response (CR) with CEA normalization. A right hepatectomy extended to segment IV was performed resulting in (FDG-)PET negative remission for 7 months. Solitary intrahepatic recurrence was effectively managed by local radiofrequent ablation following 6c FOLFIRI plus cetuximab iv. Multiple lung lesions and recurrence of pulmonary and local lymph node metastases were successfully treated with fractionated stereotactic radiotherapy (50 Gy) and iv LV/5-FU/oxaliplatin (FOLFOX) plus cetuximab finally switched to panitumumab with CR as a result. At present the patient is in persistent complete remission of her stage IV colorectal cancer, more than 5 years after initial diagnosis of the advanced disease. Multidisciplinary treatment with HAI of chemotherapy (LV/5-FU + CPT-11) plus EGFR-inhibitor can achieve CR of complex unresectable LM and can even result in hepatectomy with possible long-term survival. PMID:26064730

  2. Urokinase production by electrophoretically separated cultured human embryonic kidney cells

    NASA Technical Reports Server (NTRS)

    Kunze, M. E.; Plank, L. D.; Giranda, V.; Sedor, K.; Todd, P. W.

    1985-01-01

    Urokinase is a plasminogen activator found in urine. Relatively pure preparations have been tested in Europe, Japan and the United States for the treatment of deep vein thrombosis and other dangerous blood clots. Human embryonic kidney cell cultures have been found to produce urokinase at much higher concentrations, but less than 5% of the cells in typical cultures are producers. Since human diploid cells become senescent in culture the selection of clones derived from single cells will not provide enough material to be useful, so a bulk purification method is needed for the isolation of urokinase producing cell populations. Preparative cell electrophoresis was chosen as the method, since evidence exists that human embryonic cell cultures are richly heterogeneous with respect to electrophoretic mobility, and preliminary electrophoretic separations on the Apollo-Soyuz space flight produced cell populations that were rich in urokinase production. Similarly, erythropoietin is useful in the treatment of certain anemias and is a kidney cell duct, and electrophoretically enriched cell populations producing this product have been reported. Thus, there is a clear need for diploid human cells that produce these products, and there is evidence that such cells should be separable by free-flow cell electrophoresis.

  3. Soluble Urokinase Receptor and Chronic Kidney Disease

    PubMed Central

    Hayek, Salim S.; Sever, Sanja; Ko, Yi-An; Trachtman, Howard; Awad, Mosaab; Wadhwani, Shikha; Altintas, Mehmet M.; Wei, Changli; Hotton, Anna L.; French, Audrey L.; Sperling, Laurence S.; Lerakis, Stamatios; Quyyumi, Arshed A.; Reiser, Jochen

    2015-01-01

    BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m2 of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was −0.9 ml per minute per 1.73 m2 among participants in the lowest quartile of suPAR levels as compared with −4.2 ml per minute per 1.73 m2 among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥90 ml per minute per 1.73 m2) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m2, the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation

  4. Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover

    PubMed Central

    Gibson, P; Birchall, I; Rosella, O; Albert, V; Finch, C; Barkla, D; Young, G

    1998-01-01

    Background—The functions of urokinase in intestinal epithelia are unknown. 
Aims—To determine the relation of urokinase expressed by intestinal epithelial cells to their position in the crypt-villus/surface axis and of mucosal urokinase activity to epithelial proliferative kinetics in the distal colon. 
Methods—Urokinase expression was examined immunohistochemically in human intestinal mucosa. Urokinase activity was measured colorimetrically in epithelial cells isolated sequentially from the crypt-villus axis of the rat small intestine. In separate experiments, urokinase activity and epithelial kinetics (measured stathmokinetically) were measured in homogenates of distal colonic mucosa of 14 groups of eight rats fed diets known to alter epithelial turnover. 
Results—From the crypt base, an ascending gradient of expression and activity of urokinase was associated with the epithelial cells. Median mucosal urokinase activities in each of the dietary groups of rats correlated positively with autologous median number of metaphase arrests per crypt (r=0.68; p<0.005) and per 100 crypt cells (r=0.75; p<0.001), but not with crypt column height. 
Conclusions—Localisation of an enzyme capable of leading to digestion of cell substratum in the region where cells are loosely attached to their basement membrane, and the association of its activity with indexes of cell turnover, suggest a role for urokinase in facilitating epithelial cell loss in the intestine. 

 Keywords: urokinase; intestinal epithelium; colon; epithelial proliferation PMID:9824347

  5. Comparison of Intrahepatic and Pancreatic Perfusion on Fusion Images Using a Combined SPECT/CT System and Assessment of Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy in Advanced Pancreatic Carcinoma

    SciTech Connect

    Ikeda, Osama Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Yamashita, Yasuyuki; Takamori, Hiroshi; Kanemitsu, Keiichiro; Baba, Hideo

    2007-09-15

    Purpose. The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. Materials and Methods. CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). Results. On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median {+-} SD, 16.0 {+-} 3.7 vs. 8.0 {+-} 1.4 months; p < 0.05). Conclusions. We conclude that in patients with advanced

  6. Conditioning Effects of Chronic Infusions of Dobutamine

    PubMed Central

    Liang, Chang-Seng; Tuttle, Ronald R.; Hood, William B.; Gavras, Haralambos

    1979-01-01

    We studied the conditioning effects of chronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 μg/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 10° incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning. To assess ventricular function, we intravenously infused methoxamine both before and after conditioning. The slope of the line that related systolic aortic blood pressure and mean left atrial pressure increased in the animals conditioned with either dobutamine or exercise, indicating enhanced myocardial contractility. Left ventricular blood flow was lower in these two groups of animals than it was in the normal saline group. Left ventricular weight did not differ among the three groups. Our results show that chronic infusion of dobutamine produced cardiovascular and metabolic conditioning effects like those produced by exercise training, and further suggest that sympathetic stimulation during exercise plays a role in physical conditioning. PMID:457872

  7. Method of infusion extraction

    NASA Technical Reports Server (NTRS)

    Chang-Diaz, Franklin R. (Inventor)

    1989-01-01

    Apparatus and method of removing desirable constituents from an infusible material by infusion extraction, where a piston operating in a first chamber draws a solvent into the first chamber where it may be heated, and then moves the heated solvent into a second chamber containing the infusible material, and where infusion extraction takes place. The piston then moves the solvent containing the extract through a filter into the first chamber, leaving the extraction residue in the second chamber.

  8. Immunohistochemical Detection of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor in Canine Vascular Endothelial Tumours.

    PubMed

    Anwar, Sh; Yanai, T; Sakai, H

    2015-11-01

    Immunohistochemistry was used to assess the expression of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in 57 canine primary haemangiosarcomas (HSAs), 26 canine cutaneous haemangiomas (HAs) and in control sections of canine cutaneous granulation tissue. The correlation between uPA/uPAR expression and the Ki67 labelling index (LI) was estimated in the HSA and HA tissues. uPA was expressed by 73.2% and 75.0% of splenic HSAs and non-splenic HSAs, respectively. All HSA tissues tested expressed uPAR. Expression of both molecules was significantly higher in HSAs than in cutaneous HAs (3.8% for uPA and 30.7% for uPAR). The average Ki67 LI of the uPA(+)/uPAR(+) HSAs was significantly higher than that of uPA(-)/uPAR(+) HSAs and HA tissues (mean ± SDs 32.8 ± 15.3, 15.2 ± 7.2 and 2.1 ± 0.7, respectively; P <0.05). These results suggest that uPA and uPAR play a significant role in the malignant proliferation of canine HSA, regardless of the primary origin of the tumour. PMID:26286429

  9. Full-length soluble urokinase plasminogen activator receptor down-modulates nephrin expression in podocytes.

    PubMed

    Alfano, Massimo; Cinque, Paola; Giusti, Guido; Proietti, Silvia; Nebuloni, Manuela; Danese, Silvio; D'Alessio, Silvia; Genua, Marco; Portale, Federica; Lo Porto, Manuela; Singhal, Pravin C; Rastaldi, Maria Pia; Saleem, Moin A; Mavilio, Domenico; Mikulak, Joanna

    2015-01-01

    Increased plasma level of soluble urokinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glomerulosclerosis (FSGS). In addition, different clinical studies observed increased concentration of suPAR in various glomerular diseases and in other human pathologies with nephrotic syndromes such as HIV and Hantavirus infection, diabetes and cardiovascular disorders. Here, we show that suPAR induces nephrin down-modulation in human podocytes. This phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with the suppression of Wilms' tumor 1 (WT-1) transcription factor expression. Moreover, an antagonist of αvβ3 integrin RGDfv blocked suPAR-induced suppression of nephrin. These in vitro data were confirmed in an in vivo uPAR knock out Plaur(-/-) mice model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocytes and induces proteinuria. This study unveiled that interaction of full-length suPAR with αvβ3 integrin expressed on podocytes results in down-modulation of nephrin that may affect kidney functionality in different human pathologies characterized by increased concentration of suPAR. PMID:26380915

  10. Characterization of urokinase receptor expression by human placental trophoblasts.

    PubMed

    Zini, J M; Murray, S C; Graham, C H; Lala, P K; Karikó, K; Barnathan, E S; Mazar, A; Henkin, J; Cines, D B; McCrae, K R

    1992-06-01

    The processes of implantation and placentation are both dependent on the invasion and remodeling of the uterine endometrium and vasculature by trophoblasts. Because the secretion and autocrine binding of urokinase (uPA) appears to be a common mechanism used by cells to facilitate plasmin-dependent tissue invasion, we measured the production of uPA and expression of uPA receptors by trophoblasts. Prourokinase bound specifically, reversibly, and with high affinity to cultured trophoblasts, via the uPA epidermal growth factor-like domain. Trophoblasts derived from two first-trimester placentae bound more prourokinase than cells isolated from term placentae. Furthermore, in vitro differentiation of cultured cytotrophoblasts into syncytiotrophoblasts was associated with diminished expression of urokinase receptors and a parallel decrease in the cellular content of uPA receptor mRNA. Trophoblasts also secreted prourokinase and plasminogen activator inhibitors types 1 and 2 (PAI-1 and PAI-2). Although prourokinase was secreted in amounts sufficient to endogenously saturate trophoblast uPA receptors, trophoblasts secreted greater amounts of PAI-1 and PAI-2 than uPA, and no net plasminogen activator activity was detected in trophoblast conditioned medium. In contrast, plasminogen added directly to cultured trophoblasts was readily converted to plasmin. Although the invasion and remodeling of uterine tissues by trophoblasts is a complex process dependent on several proteases of varying specificity, our findings suggest that the expression and modulation of urokinase receptors on the trophoblast cell surface may play an important role in this process. PMID:1316787

  11. Initial Results of Catheter-Directed Ultrasound-Accelerated Thrombolysis for Thromboembolic Obstructions of the Aortofemoral Arteries: A Feasibility Study

    SciTech Connect

    Schrijver, A. Marjolein; Reijnen, Michel M. P. J.; Oostayen, Jacques A. van; Hoksbergen, Arjan W. J.; Lely, Rutger J.; Leersum, Marc van; Vries, Jean-Paul P. M. de

    2012-04-15

    Purpose: This article reports the 30-day technical and clinical outcome of ultrasound (US)-accelerated thrombolysis in patients with aortofemoral arterial thromboembolic obstructions. Methods: A prospective cohort study was conducted from December 2008 to December 2009 of patients who were treated with US-accelerated thrombolysis for thromboembolic obstructions of aortofemoral arteries or bypasses. Urokinase was infused in a dosage of 100,000 IU per hour. Twice daily, a control angiography was performed. Thirty-day follow-up consisted of duplex scanning, combined with magnetic resonance angiography. Results: The study included 21 consecutive patients (20 men; median age, 66 (range, 52-80) years) with 24% artery versus 76% bypass occlusions. Median duration of symptoms was 11 (range, 7-140) days. Median occlusion length was 32 (range, 6-80) cm. In 20 patients (95%), an US-accelerated thrombolysis catheter could be successfully placed. In one patient, placement of an US-accelerated thrombolysis catheter was technically not feasible, and therefore a standard catheter was placed. Median thrombolysis time was 26.5 (range, 8.5-72) hours. Complete thrombolysis (>95% lysis of thrombus) was achieved in 20 patients; in 9 patients within 24 hours. Median ankle-brachial index (ABI) increased from 0.28 (range, 0-0.85) to 0.91 (range, 0.58-1.35). One patient had a thromboembolic complication and needed surgical intervention. No hemorrhagic complications, and no deaths occurred. At 30-day follow-up, 17 of 21 patients (81%) had a patent artery or bypass. Conclusions: This feasibility study showed a high technical success rate of US-accelerated thrombolysis for aortofemoral arterial obstructions. US-accelerated thrombolysis led to complete lysis within 24 hours in almost half of patients, with a low 30-day major complication rate.

  12. Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up

    PubMed Central

    Guan, Yong-song; Liu, Yuan; Zou, Qing; He, Qing; La, Zi; Yang, Lin; Hu, Ying

    2009-01-01

    Objective: In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) injection in patients with advanced non-small-cell lung cancer (NSCLC) in the combination with the therapy of bronchial arterial infusion (BAI). Methods: A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 (the combo group), while the remaining 39 were treated with only BAI (the control group). Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer Institute’s Common Toxicity Criteria and response evaluation criteria in solid tumor (RECIST), respectively. Time to progression (TTP) and survival rates were also analyzed by Kaplan-Meier method. Results: In the combo group, 19 patients received a total of 49 injections of rAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia (P<0.05) but more arthralgia, fever, influenza-like symptom, and myalgia (P<0.05), compared with the control group. The overall response rates (complete response (CR)+partial response (PR)) were 47.3% and 38.4% for the combo group and the control group, respectively (P>0.05). Patients in the combo group had a longer TTP than those in the control group (a median 7.75 vs 5.5 months, P=0.018). However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, compared with 92.31%, 69.23%, and 38.83% in the control group (P=0.224). Conclusion: Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the quality of life and delayed

  13. Hepatic transcatheter arterial chemoembolization alternating with systemic protracted continuous infusion 5-fluorouracil for gastrointestinal malignancies metastatic to liver: a phase II trial of the Puget Sound Oncology Consortium (PSOC 1104).

    PubMed

    Bavisotto, L M; Patel, N H; Althaus, S J; Coldwell, D M; Nghiem, H V; Thompson, T; Storer, B; Thomas, C R

    1999-01-01

    We assessed a regimen of alternating regional and systemic therapy in patients with gastrointestinal malignancies with liver-dominant metastases for feasibility, toxicity, response rate, response duration, patterns of progression, and progression-free and overall survival. Regional therapy comprised selective hepatic transcatheter arterial chemoembolization (TACE) using a suspension of cisplatin and particulate polyvinyl alcohol. This procedure was delivered between cycles of protracted continuous infusion 5-fluorouracil (PCI-5FU) as systemic chemotherapy. Patient eligibility criteria included: (a) having histologically documented adenocarcinoma arising from a gastrointestinal primary site with unresectable liver metastases bidimensionally measurable on computerized tomography scan; (b) age greater than 18 years; and (c) performance status 0-2 (Zubrod). PCI-5FU (250 mg/m2/day) was administered i.v. for 28 days, followed by the first TACE (TACE 1) delivered to the hepatic artery supplying the lobe with the greatest tumor burden. Restaging was performed before TACE 2 and TACE 3, which followed at monthly intervals. PCI-5FU for 21 days was sandwiched between each of the TACE treatments. After the final TACE, maintenance PCI-5FU was given for 28 days of each 35-day cycle until toxicity or progression. Between December 23, 1991, and January 19, 1995, 32 patients were registered in this trial, of whom 27 were eligible; 20 completed one or more treatment cycles and were evaluable for radiographic response. Patients with colorectal liver metastases predominated (74%). Twelve (44%) of 27 patients had failed one or more prior treatment regimens. There were no treatment-related deaths, and hematological and hepatic toxicities were generally manageable and reversible. Two patients, however, developed hepatic abscesses requiring drainage, and one patient developed an infarcted gallbladder, which necessitated cholecystectomy. There were no patients with complete responses; there

  14. A Series of Cerebral Venous Sinus Thromboses Treated with Intra-Arterial tPA infused over Ten Hours with a 0.027-inch Catheter and Literature Review

    PubMed Central

    Ziu, Endrit; Haley, O'Hara; Ibrahimi, Muhammad; Simon, Scott

    2016-01-01

    Cerebral venous sinus thrombosis (CVST) can have devastating results, with mortality reported in 44% of cases. No randomized trials exist in order to define what qualifies as failure of conservative therapy, and there is no specific intervention to date which is considered safe and effective. Case series suggest that thrombolysis infusion is safer than thrombectomy, but methods of administration, dose, and duration of therapy tend to vary widely. We present three consecutive CVST patients treated with heparin who suffered both clinical and radiographic deterioration, and went on to have endovascular therapy. Each patient was successfully recanalized by placing a 0.027-inch microcatheter at the proximal portion of the thrombus and infusing 20 mg of alteplase dissolved in 1 liter of normal saline infused at 100 ml per hour for an infusion of 2 mg of alteplase per hour for ten hours.  PMID:27462480

  15. Successful Intra-Arterial Thrombolysis for Acute Ischemic Stroke in the Immediate Postpartum Period: Case Report

    SciTech Connect

    Mendez, Jose C. Masjuan, J.; Garcia, N.; Lecinana, M. de

    2008-01-15

    Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period.

  16. Programmable physiological infusion

    NASA Technical Reports Server (NTRS)

    Howard, W. H.; Young, D. R.; Adachi, R. R. (Inventor)

    1974-01-01

    A programmable physiological infusion device and method are provided wherein a program source, such as a paper tape, is used to actuate an infusion pump in accordance with a desired program. The system is particularly applicable for dispensing calcium in a variety of waveforms.

  17. Purification of urokinase by combined cation exchanger and affinity chromatographic cartridges.

    PubMed

    Hou, K C; Zaniewski, R

    1990-02-23

    Crude urokinase from human urine processed through foam flotation and ammonium sulfate precipitation containing 720 National Health Institute Committee on Thrombolytic Agents U/mg activity was purified by an SP cation exchanger followed by a zinc-chelated affinity chromatographic cartridge. The cartridges were of a radial-flow type formed by using acrylic and cellulose composite matrices. The high rigidity of the matrix structure permits fast flow of protein solutions (liters per minute) and thus allows processing of a large volume of crude urokinase under low operating pressures. A greater than six-fold increase in specific enzyme activity of urokinase was achieved by adsorbing and eluting 1 l of a 3 mg/ml crude urokinase solution on an SP cartridge. The eluent was further purified by passing through a zinc-chelated affinity cartridge to achieve greater than a eighteen-fold increase in urokinase specific activity. This report demonstrates the combined use of a cation exchanger with zinc-chelated chromatographic cartridges in purifying urokinase on a relatively large scale. The relationship between the amount of zinc chelated in the matrix to its effect on urokinase purification is also discussed. PMID:2329161

  18. Single-chain urokinase in empyema induced by Pasturella multocida.

    PubMed

    Idell, Steven; Jun Na, Moon; Liao, Huai; Gazar, A E; Drake, Wonder; Lane, Kirk B; Koenig, Kathy; Komissarov, Andrey; Tucker, Torry; Light, Richard W

    2009-10-01

    Intrapleural fibrin deposition and subsequent fibrosis characterize evolving empyema and contribute to the morbidity associated with this condition. Single-chain urokinase (scuPA) is proenzyme form of the urokinase plasminogen activator, which has recently been shown to effectively clear intrapleural loculation in tetracycline-induced pleurodesis in rabbits. The authors therefore hypothesized that scuPA could likewise improve intrapleural injury associated with empyema. The authors used a rabbit model of empyema induced by intrapleural administration of Pasturella multocida to test this hypothesis and determined the effects of intrapleural scuPA on pleural fluids indices of inflammation and intrapleural fibrosis. The authors found that intrapleural administration of scuPA was well tolerated, generated readily detectable fibrinolytic activity in the empyema fluids and did not induce intrapleural or systemic bleeding. Pleural fluid volume, intrapleural protein, and D-dimer concentrations were increased at 24 and 48 hours (P < .01, respectively) after induction of empyema. Intrapleural loculation did not occur in the scuPA- or vehicle control-treated animals and there was no significant change in the pleural empyema or thickening scores. These findings confirm that intrapleural scuPA generates fibrinolysis in empyema fluids but does not alter fibrotic repair at the pleural surface or the intensity of intrapleural inflammation in this empyema model. PMID:19895321

  19. Nuclear translocation of urokinase-type plasminogen activator.

    PubMed

    Stepanova, Victoria; Lebedeva, Tatiana; Kuo, Alice; Yarovoi, Serge; Tkachuk, Sergei; Zaitsev, Sergei; Bdeir, Khalil; Dumler, Inna; Marks, Michael S; Parfyonova, Yelena; Tkachuk, Vsevolod A; Higazi, Abd Al-Roof; Cines, Douglas B

    2008-07-01

    Urokinase-type plasminogen activator (uPA) participates in diverse (patho)physiological processes through intracellular signaling events that affect cell adhesion, migration, and proliferation, although the mechanisms by which these occur are only partially understood. Here we report that upon cell binding and internalization, single-chain uPA (scuPA) translocates to the nucleus within minutes. Nuclear translocation does not involve proteolytic activation or degradation of scuPA. Neither the urokinase receptor (uPAR) nor the low-density lipoprotein-related receptor (LRP) is required for nuclear targeting. Rather, translocation involves the binding of scuPA to the nucleocytoplasmic shuttle protein nucleolin through a region containing the kringle domain. RNA interference and mutational analysis demonstrate that nucleolin is required for the nuclear transport of scuPA. Furthermore, nucleolin is required for the induction smooth muscle alpha-actin (alpha-SMA) by scuPA. These data reveal a novel pathway by which uPA is rapidly translocated to the nucleus where it might participate in regulating gene expression. PMID:18337556

  20. Saline infusion sonohysterography.

    PubMed

    2004-01-01

    Saline infusion sonohysterography consists of ultrasonographic imaging of the uterus and uterocervical cavity, using real-time ultrasonography during injection of sterile saline into the uterus. When properly performed, saline infusion sonohysterography can provide information about the uterus and endometrium. The most common indication for sonohysterography is abnormal uterine bleeding. sonohysterography should not be performed in a woman who is pregnant or could be pregnant or in a woman with a pelvic infection or unexplained pelvic tenderness. Physicians who perform or supervise diagnostic saline infusion sonohysterograpy should have training, experience, and demonstrated competence in gynecologic ultrasonography and saline infusion sonohysterography. Portions of this document were developed jointly with the American College of Radiology and the American Institute of Ultrasound in Medicine. PMID:14968760

  1. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Performance testing carried out in the development of the prototype zero-g fluid infusion system is described and summarized. Engineering tests were performed in the course of development, both on the original breadboard device and on the prototype system. This testing was aimed at establishing baseline system performance parameters and facilitating improvements. Acceptance testing was then performed on the prototype system to verify functional performance. Acceptance testing included a demonstration of the fluid infusion system on a laboratory animal.

  2. Structural investigations of recombinant urokinase growth factor-like domain.

    PubMed

    Beloglazova, I B; Beabealashvilli, R Sh; Gursky, Ya G; Bocharov, E V; Mineev, K S; Parfenova, E V; Tkachuk, V A

    2013-05-01

    Urokinase-type plasminogen activator (uPA) is a serine protease that converts the plasminogen zymogen into the enzymatically active plasmin. uPA is synthesized and secreted as the single-chain molecule (scuPA) composed of an N-terminal domain (GFD) and kringle (KD) and C-terminal proteolytic (PD) domains. Earlier, the structure of ATF (which consists of GFD and KD) was solved by NMR (A. P. Hansen et al. (1994) Biochemistry, 33, 4847-4864) and by X-ray crystallography alone and in a complex with the soluble form of the urokinase receptor (uPAR, CD87) lacking GPI (C. Barinka et al. (2006) J. Mol. Biol., 363, 482-495). According to these data, GFD contains two β-sheet regions oriented perpendicularly to each other. The area in the GFD responsible for binding to uPAR is localized in the flexible Ω-loop, which consists of seven amino acid residues connecting two strings of antiparallel β-sheet. It was shown by site-directed mutagenesis that shortening of the Ω-loop length by one amino acid residue leads to the inability of GFD to bind to uPAR (V. Magdolen et al. (1996) Eur. J. Biochem., 237, 743-751). Here we show that, in contrast to the above-mentioned studies, we found no sign of the β-sheet regions in GFD in our uPA preparations either free or in a complex with uPAR. The GFD seems to be a rather flexible and unstructured domain, demonstrating in spite of its apparent flexibility highly specific interaction with uPAR both in vitro and in cell culture experiments. Circular dichroism, tryptophan fluorescence during thermal denaturation of the protein, and heteronuclear NMR spectroscopy of ¹⁵N/¹³C-labeled ATF both free and in complex with urokinase receptor were used to judge the secondary structure of GFD of uPA. PMID:23848154

  3. Urokinase and type I plasminogen activator inhibitor production by normal human hepatocytes: modulation by inflammatory agents.

    PubMed

    Busso, N; Nicodeme, E; Chesne, C; Guillouzo, A; Belin, D; Hyafil, F

    1994-07-01

    We examined the effects of inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha and transforming growth factor-beta) on the plasminogen activator system (urokinase, tissue-type plasminogen activator, type 1 plasminogen activator inhibitor) in primary cultures of human hepatocytes. We show that interleukin-1 beta and tumor necrosis factor-alpha increase urokinase-type plasminogen activator production, reinforcing the concept that increased urokinase production is associated with inflammatory processes. By contrast, the same agents (i.e., interleukin-1 beta and tumor necrosis factor-alpha) do not stimulate plasminogen activator inhibitor type 1 production. This latter observation rules out hepatocytes as a major cellular source of plasmatic plasminogen activator inhibitor type 1 during acute-phase-related responses. Among the inflammatory agents used, transforming growth factor-beta was found to be the most effective modulator of both urokinase-type plasminogen activator and plasminogen activator inhibitor type 1, inducing severalfold increases of activity of urokinase-type plasminogen activator, antigen and the corresponding mRNA and increasing plasminogen activator inhibitor type 1 antigen and mRNA levels. Urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 modulation by transforming growth factor-beta may play a critical role in hepatic pathophysiology. PMID:8020888

  4. Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression.

    PubMed Central

    Rao, N K; Shi, G P; Chapman, H A

    1995-01-01

    Binding of urokinase to the glycolipid-anchored urokinase receptor (uPAR) has been implicated in macrophage differentiation. However, no biochemical markers of differentiation have yet been directly linked to uPAR occupancy. As extensive changes in proteolytic profile characterize monocytic differentiation, we have examined the role of uPAR occupancy on protease expression by differentiating phagocytes. Antibodies to either urokinase or to uPAR that prevent receptor binding inhibited induction of cathepsin B in cultured monocytes and both cathepsin B and 92-kD gelatinase mRNA and protein in phorbol diester-stimulated myeloid cells. Mannosamine, an inhibitor of glycolipid anchor assembly, also blocked protease expression. Anti-catalytic urokinase antibodies, excess inactive urokinase, or aprotinin had no effect, indicating that receptor occupancy per se regulated protease expression. Antibodies to the integrins CD11a and CD29 or to the glycolipid-anchored proteins CD14 and CD55 also had no effect. Protease induction was independent of matrix attachment. Antibodies to urokinase or uPAR affected neither the decrease in cathepsin G nor the increase in tumor necrosis factor-alpha in phorbol ester-stimulated cells. These data establish that uPAR is a multifunctional receptor, not only promoting pericellular proteolysis and matrix attachment, but also effecting cysteine- and metallo-protease expression during macrophage differentiation. Images PMID:7615819

  5. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    Hammond, J. C.

    1975-01-01

    Development of a fluid infusion system was undertaken in response to a need for an intravenous infusion device operable under conditions of zero-g. The initial design approach, pursued in the construction of the first breadboard instrument, was to regulate the pressure of the motive gas to produce a similar regulated pressure in the infusion liquid. This scheme was not workable because of the varying bag contact area, and a major design iteration was made. A floating sensor plate in the center of the bag pressure plate was made to operate a pressure regulator built into the bellows assembly, effectively making liquid pressure the directly controlled variable. Other design changes were made as experience was gained with the breadboard. Extensive performance tests were conducted on both the breadboard and the prototype device; accurately regulated flows from 6 m1/min to 100 m1/min were achieved. All system functions were shown to operate satisfactorily.

  6. Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

    PubMed Central

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan; Wei, Hao; Liu, Shihui; Lund, Ida K.; Høyer-Hansen, Gunilla; Dichek, David A.

    2015-01-01

    Aims Elevated activity of urokinase plasminogen activator (uPA) and MMPs in human arteries is associated with accelerated atherosclerosis, aneurysms, and plaque rupture. We used Apoe-null mice with macrophage-specific uPA overexpression (SR-uPA mice; a well-characterized model of protease-accelerated atherosclerosis) to investigate whether systemic inhibition of proteolytic activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis and aortic dilation. Methods and results SR-uPA mice were fed a high-fat diet for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1) or a control antibody. mU1-treated mice were also compared with PBS-treated non-uPA-overexpressing Apoe-null mice. Other SR-uPA mice were treated with one of three doses of a limited-spectrum synthetic MMP inhibitor (XL784) or vehicle. mU1 reduced aortic root intimal lesion area (20%; P = 0.05) and aortic root circumference (12%; P = 0.01). All XL784 doses reduced aortic root intimal lesion area (22–29%) and oil-red-O-positive lesion area (36–42%; P < 0.05 for all doses and both end points), with trends towards reduced aortic root circumference (6–10%). Neither mU1 nor XL784 significantly altered percent aortic surface lesion coverage. Several lines of evidence identified MMP-13 as a mediator of uPA-induced aortic MMP activity. Conclusions Pharmacological inhibition of either uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition decreased aortic dilation. Differential effects of both agents on aortic root vs. distal aortic atherosclerosis suggest prevention of atherosclerosis progression vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for treating atherosclerosis. PMID:25616415

  7. Liposome distribution after intravenous and selective intraarterial infusion in dogs

    SciTech Connect

    Wright, K.C.; Kasi, L.P.; Jahns, M.S.; Hashimoto, S.; Wallace, S. )

    1990-09-01

    In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels.

  8. Rescue therapy with terlipressin by continuous infusion in a child with catecholamine-resistant septic shock.

    PubMed

    Zeballos, Gonzalo; López-Herce, Jesús; Fernández, Carmen; Brandstrup, Kay B; Rodríguez-Núñez, Antonio

    2006-01-01

    A 2-month-old female infant presented with septic shock, refractory to high doses of catecholamines. Continuous infusion of terlipressin at a rate of 10 mcg/kgh produced a significant increase in the mean arterial pressure that was evident within half and hour, so allowing a reduction in the rate of catecholamine infusion. However, 18 h later, the blood pressure fell again and finally the patient died. This case shows the potential value of terlipressin infusion to restore normal mean arterial pressure in children with vasodilatory shock and hypotension refractory to catecholamines. PMID:16325320

  9. Involvement of the Soluble Urokinase Receptor in Chondrosarcoma Cell Mobilization

    PubMed Central

    Bifulco, Katia; Longanesi-Cattani, Immacolata; Masucci, Maria Teresa; De Chiara, Annarosaria; Fazioli, Flavio; Di Carluccio, Gioconda; Pirozzi, Giuseppe; Gallo, Michele; La Rocca, Antonello; Apice, Gaetano; Rocco, Gaetano; Carriero, Maria Vincenza

    2011-01-01

    High levels of urokinase receptor (uPAR) in tissue and serum of patients with chondrosarcoma correlate with poor prognosis. First, we analyzed the uPAR levels in tissues and plasma of five patients affected by chondrosarcoma. Interestingly, very high levels of uPAR and its soluble forms (SuPAR) were found on tumor cell surfaces and plasma, respectively, of two patients with lung metastases. Therefore, to investigate the role of SuPAR in chondrosaromas, we generated a primary cell culture from a chondrosarcoma tissue overexpressing uPAR on cell surfaces. We found that chondrosarcoma-like primary culture cells release a large amount of SuPAR in the medium. In vitro, SuPAR elicits chondrosarcoma cell migration likely through its uPAR88-92 sequence, since the DII88-183 or DIIDIIR88-284 uPAR domains retain motogen effect whereas DI1-87 or DIII184-284 domains, both lacking the uPAR88-92 sequence, are ineffective. Chondrosarcoma cells cross matrigel in response to SuPAR, and their invasion capability is abrogated by RERF peptide which inhibits uPAR88-92 signalling. These findings assign a role to uPAR in mobilizing chondrosarcoma cells and suggest that RERF peptide may be regarded as a prototype to generate new therapeutics for the chondrosarcoma treatment. PMID:21253510

  10. Application of Molecular Modeling to Urokinase Inhibitors Development

    PubMed Central

    Sulimov, V. B.; Katkova, E. V.; Oferkin, I. V.; Sulimov, A. V.; Romanov, A. N.; Roschin, A. I.; Beloglazova, I. B.; Plekhanova, O. S.; Tkachuk, V. A.; Sadovnichiy, V. A.

    2014-01-01

    Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program), postprocessing (DISCORE program), direct generalized docking (FLM program), and the application of the quantum chemical calculations (MOPAC package), search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM. PMID:24967388

  11. Secretion of macrophage urokinase plasminogen activator is dependent on proteoglycans.

    PubMed

    Pejler, Gunnar; Winberg, Jan-Olof; Vuong, Tram T; Henningsson, Frida; Uhlin-Hansen, Lars; Kimata, Koji; Kolset, Svein O

    2003-10-01

    The importance of proteoglycans for secretion of proteolytic enzymes was studied in the murine macrophage cell line J774. Untreated or 4beta-phorbol 12-myristate 13-acetate (PMA)-stimulated macrophages were treated with hexyl-beta-d-thioxyloside to interfere with the attachment of glycosaminoglycan chains to their respective protein cores. Activation of the J774 macrophages with PMA resulted in increased secretion of trypsin-like serine proteinase activity. This activity was completely inhibited by plasminogen activator inhibitor 1 and by amiloride, identifying the activity as urokinase plasminogen activator (uPA). Treatment of both the unstimulated or PMA-stimulated macrophages with xyloside resulted in decreased uPA activity and Western blotting analysis revealed an almost complete absence of secreted uPA protein after xyloside treatment of either control- or PMA-treated cells. Zymography analyses with gels containing both gelatin and plasminogen confirmed these findings. The xyloside treatment did not reduce the mRNA levels for uPA, indicating that the effect was at the post-translational level. Treatment of the macrophages with xylosides did also reduce the levels of secreted matrix metalloproteinase 9. Taken together, these findings indicate a role for proteoglycans in the secretion of uPA and MMP-9. PMID:14511379

  12. Temporary elimination of orthostatic hypotension by norepinephrine infusion.

    PubMed

    Goldstein, David S; Sewell, LaToya; Holmes, Courtney; Pechnik, Sandra; Diedrich, André; Robertson, David

    2012-12-01

    A cardinal manifestation of chronic autonomic failure is neurogenic orthostatic hypotension (OH), which often is associated with supine hypertension, posing a therapeutic dilemma. We report here success in a first step toward development of a "prosthetic baroreceptor system" to maintain blood pressure during orthostasis without worsening supine hypertension. In all of four patients with neurogenic OH, titrated i.v. NE infusion kept directly recorded intra-arterial pressure at or above baseline during progressive head-up tilt. We conclude that titrated i.v. NE infusion temporarily eliminates OH. PMID:22983778

  13. Feeding Artery of Laryngeal and Hypopharyngeal Cancers: Role of the Superior Thyroid Artery in Superselective Intraarterial Chemotherapy

    SciTech Connect

    Terayama, Noboru Sanada, Junichiro; Matsui, Osamu; Kobayashi, Satoshi; Kawashima, Hiroko; Yamashiro, Masashi; Takanaka, Tsuyoshi; Kumano, Tomoyasu; Yoshizaki, Tomokazu; Furukawa, Mitsuru

    2006-08-15

    The purpose of this study was to elucidate the role of the superior thyroid artery in intra-arterial infusion chemotherapy for laryngeal and hypopharyngeal cancers. Thirty-nine patients with laryngeal cancer and 29 patients with hypopharyngeal cancer underwent intra-arterial infusion chemotherapy. We performed a retrospective analysis of the feeding arteries confirmed by computed tomography during selective arteriography and compared the results with the extent of the tumors. In 14 of 39 laryngeal and 15 of 29 hypopharyngeal cancers, the tumor did not cross the midline (group 1). In the remaining 25 and 14 cancers, respectively, the tumor crossed the midline or located in the center (group 2). For 13 of 14 laryngeal and 7 of 15 hypopharyngeal cancers in group 1 and for 6 of 25 laryngeal cancers in group 2, the entire tumor was contrast enhanced by the ipsilateral superior thyroid and/or superior laryngeal artery. For 12 of 25 laryngeal and 1 of 14 hypopharyngeal cancers in group 2, the entire tumor was contrast enhanced by the bilateral superior thyroid artery. For the other patients, infusion via the other arterial branches such as the inferior thyroid and the lingual arteries were needed to achieve contrast enhancement of the entire tumor. Superselective intra-arterial chemotherapy for laryngeal cancer from the superior thyroid artery is appropriate, whereas that for hypopharyngeal cancer is less sufficient. To accomplish contrast enhancement of the entire tumor, additional intra-arterial infusion from other arteries such as the inferior thyroid artery is often necessary.

  14. Cerebral Critical Closing Pressure During Infusion Tests.

    PubMed

    Varsos, Georgios V; Czosnyka, Marek; Smielewski, Peter; Garnett, Matthew R; Liu, Xiuyun; Adams, Hadie; Pickard, John D; Czosnyka, Zofia

    2016-01-01

    We studied possible correlations between cerebral hemodynamic indices based on critical closing pressure (CrCP) and cerebrospinal fluid (CSF) compensatory dynamics, as assessed during lumbar infusion tests. Our data consisted of 34 patients with normal-pressure hydrocephalus who undertook an infusion test, in conjunction with simultaneous transcranial Doppler ultrasonography (TCD) monitoring of blood flow velocity (FV). CrCP was calculated from the monitored signals of ICP, arterial blood pressure (ABP), and FV, whereas vascular wall tension (WT) was estimated as CrCP - ICP. The closing margin (CM) expresses the difference between ABP and CrCP. ICP increased during infusion from 6.67 ± 4.61 to 24.98 ± 10.49 mmHg (mean ± SD; p < 0.001), resulting in CrCP rising by 22.93 % (p < 0.001), with WT decreasing by 11.33 % (p = 0.005) owing to vasodilatation. CM showed a tendency to decrease, albeit not significantly (p = 0.070), because of rising ABP (9.12 %; p = 0.005), and was significantly different from zero for the whole duration of the tests (52.78 ± 22.82 mmHg; p < 0.001). CM at baseline correlated inversely with brain elasticity (R = -0.358; p = 0.038). Neither CrCP nor WT correlated with CSF compensatory parameters. Overall, CrCP increases and WT decreases during infusion tests, whereas CM at baseline pressure may act as a characterizing indicator of the cerebrospinal compensatory reserve. PMID:27165909

  15. Effects and mechanism analysis of combined infusion by levosimendan and vasopressin on acute lung injury in rats septic shock.

    PubMed

    Wang, Xuebing; Ma, Shaolin; Liu, Yang; Xu, Wei; Li, Zhanxia

    2014-12-01

    This research is aimed to discover the influence and underling mechanism of combined infusion of arginine vasopressin with levosimendan on acute lung injury in rat septic shock with norepinephrine supplemented. The traditional fecal peritonitis-induced septic shock model was undergone in rats for study. It is observed that the combined infusion supplemented with norepinephrine brought about a lower mean pulmonary artery pressure; lower high-mobility group box 1 levels, pulmonary levels of interleukin-6, and arterial total nitrate/nitrite; lower apoptotic cells scores and total histological scores; but higher pulmonary gas exchange when compared with the separate infusion group and norepinephrine group. This therapy shows potential clinical beneficial assistance in sepsis-induced acute lung injury. The results suggest the mechanism of such effect is through abating pulmonary artery pressure, and more importantly suppressing inflammatory responses in lung when compared with norepinephrine infusion group and the separate infusion of levosimendan or vasopressin alone. PMID:25002345

  16. Imaging Active Urokinase Plasminogen Activator in Prostate Cancer

    PubMed Central

    LeBeau, Aaron M.; Sevillano, Natalia; Markham, Kate; Winter, Michael B.; Murphy, Stephanie T.; Hostetter, Daniel R.; West, James; Lowman, Henry; Craik, Charles S.; VanBrocklin, Henry F.

    2015-01-01

    The increased proteolytic activity of membrane-bound and secreted proteases on the surface of cancer cells and in the transformed stroma is a common characteristic of aggressive metastatic prostate cancer. We describe here the development of an active site-specific probe for detecting a secreted peritumoral protease expressed by cancer cells and the surrounding tumor microenvironment. Using a human fragment antigen binding phage display library, we identified a human antibody termed U33 that selectively inhibited the active form of the protease urokinase plasminogen activator (uPA, PLAU). In the full-length immunoglobulin form, U33 IgG labeled with near-infrared fluorophores or radionuclides allowed us to non-invasively detect active uPA in prostate cancer xenograft models using optical and single-photon emission computed tomography (SPECT) imaging modalities. U33 IgG labeled with 111In had a remarkable tumor uptake of 43.2% injected dose per gram (%ID/g) 72hr post tail vein injection of the radiolabeled probe in subcutaneous xenografts. Additionally, U33 was able to image active uPA in small soft-tissue and osseous metastatic lesions using a cardiac dissemination prostate cancer model that recapitulated metastatic human cancer. The favorable imaging properties were the direct result of U33 IgG internalization through an uPA receptor mediated mechanism where U33 mimicked the function of the endogenous inhibitor of uPA to gain entry into the cancer cell. Overall, our imaging probe targets a prostate cancer-associated protease, through a unique mechanism, allowing for the non-invasive preclinical imaging of prostate cancer lesions. PMID:25672980

  17. Regulation of epithelial sodium channels in urokinase plasminogen activator deficiency

    PubMed Central

    Chen, Zaixing; Zhao, Runzhen; Zhao, Meimi; Liang, Xinrong; Bhattarai, Deepa; Dhiman, Rohan; Shetty, Sreerama; Idell, Steven

    2014-01-01

    Epithelial sodium channels (ENaC) govern transepithelial salt and fluid homeostasis. ENaC contributes to polarization, apoptosis, epithelial-mesenchymal transformation, etc. Fibrinolytic proteases play a crucial role in virtually all of these processes and are elaborated by the airway epithelium. We hypothesized that urokinase-like plasminogen activator (uPA) regulates ENaC function in airway epithelial cells and tested that possibility in primary murine tracheal epithelial cells (MTE). Both basal and cAMP-activated Na+ flow through ENaC were significantly reduced in monolayers of uPA-deficient cells. The reduction in ENaC activity was further confirmed in basolateral membrane-permeabilized cells. A decrease in the Na+-K+-ATPase activity in the basolateral membrane could contribute to the attenuation of ENaC function in intact monolayer cells. Dysfunctional fluid resolution was seen in uPA-disrupted cells. Administration of uPA and plasmin partially restores ENaC activity and fluid reabsorption by MTEs. ERK1/2, but not Akt, phosphorylation was observed in the cells and lungs of uPA-deficient mice. On the other hand, cleavage of γ ENaC is significantly depressed in the lungs of uPA knockout mice vs. those of wild-type controls. Expression of caspase 8, however, did not differ between wild-type and uPA−/− mice. In addition, uPA deficiency did not alter transepithelial resistance. Taken together, the mechanisms for the regulation of ENaC by uPA in MTEs include augmentation of Na+-K+-ATPase, proteolysis, and restriction of ERK1/2 phosphorylation. We demonstrate for the first time that ENaC may serve as a downstream signaling target by which uPA controls the biophysical profiles of airway fluid and epithelial function. PMID:25172911

  18. Urokinase plasminogen activator gene deficiency inhibits fracture cartilage remodeling.

    PubMed

    Popa, Nicoleta L; Wergedal, Jon E; Lau, K-H William; Mohan, Subburaman; Rundle, Charles H

    2014-03-01

    Urokinase plasminogen activator (uPA) regulates a proteolytic cascade of extracellular matrix degradation that functions in tissue development and tissue repair. The development and remodeling of the skeletal extracellular matrix during wound healing suggests that uPA might regulate bone development and repair. To determine whether uPA functions regulate bone development and repair, we examined the basal skeletal phenotype and endochondral bone fracture repair in uPA-deficient mice. The skeletal phenotype of uPA knockout mice was compared with that of control mice under basal conditions by dual-energy X-ray absorptiometry and micro-CT analysis, and during femur fracture repair by micro-CT and histological examination of the fracture callus. No effects of uPA gene deficiency were observed in the basal skeletal phenotype of the whole body or the femur. However, uPA gene deficiency resulted in increased fracture callus cartilage abundance during femur fracture repair at 14 days healing. The increase in cartilage corresponded to reduced tartrate-resistant acid phosphatase (TRAP) staining for osteoclasts in the uPA knockout fracture callus at this time, consistent with impaired osteoclast-mediated remodeling of the fracture cartilage. CD31 staining was reduced in the knockout fracture tissues at this time, suggesting that angiogenesis was also reduced. Osteoclasts also colocalized with CD31 expression in the endothelial cells of the fracture tissues during callus remodeling. These results indicate that uPA promotes remodeling of the fracture cartilage by osteoclasts that are associated with angiogenesis and suggest that uPA promotes angiogenesis and remodeling of the fracture cartilage at this time of bone fracture repair. PMID:23700285

  19. [Intraosseous infusion for adults].

    PubMed

    Leidel, B A; Kirchhoff, C

    2008-04-01

    Intraosseous (IO) infusion methods have been common for emergency treatment in infants and children for years. The role of IO access in adults is however much less clear, but its importance in this patient group is increasing, and different devices are available today. Each device has strengths and weaknesses, but all achieve rapid vascular access even in challenging situations. The potential of IO access regarding both therapeutic and diagnostic options has been shown in several operational studies in and out of hospital. Insertion times require between 1 and 2 min in most cases, while insertion and handling of the IO access devices seem to be easy and reliable. The flow rates of IO access devices for adults are lower than those of large-bore peripheral intravenous catheters, but fluid resuscitation is possible in most cases at least with pressure bag infusion systems. Most drugs administered intravenously can be given intraosseously in equivalent dosages and with the same effects. Nevertheless the limitations and risks of IO access routes need to be considered for each application. Rapid IO access is now possible in all age groups, and the 2005 AHA Guidelines favor it over drug administration via the endotracheal tube. PMID:18250995

  20. Platelet activation during angiotensin II infusion in healthy volunteers.

    PubMed

    Larsson, P T; Schwieler, J H; Wallén, N H

    2000-01-01

    The present study was undertaken to evaluate the effects of an intravenous infusion of angiotensin II (10 ng/kg per min) on platelet function and coagulation in vivo in 18 healthy males. The infusion increased mean arterial pressure by 23+/-2 mm Hg. Plasma beta-thromboglobulin levels, reflecting platelet secretion, increased by 66+/-24% during the infusion, as did also platelet surface expression of P-selectin as measured by flow cytometry. Platelet fibrinogen binding increased, whereas platelet aggregability, assessed by ex vivo filtragometry, was unaltered. Angiotensin II caused mild activation of the coagulation cascade with increases in plasma levels of thrombin-antithrombin complex and prothrombin fragment F1 + 2. In conclusion, angiotensin II has mild platelet-activating effects in vivo and also enhances coagulation. Markers of platelet secretion are significantly increased, whereas markers of platelet aggregability are less affected. The clinical relevance of these findings remains to be clarified. PMID:10691100

  1. Urokinase-Treated Antithrombogenic Drains and Optimized Drain Placement in Endoscopic Lumbar Decompressive Surgery.

    PubMed

    Nakamura, Shu; Ikeda, Shoji; Taguchi, Mitsuto

    2016-07-01

    Background Spinal epidural hematoma (SEH) frequently occurs after microendoscopic decompressive laminotomy (MEDL), and a drain may not be functioning sufficiently. Objective To reduce the incidence of SEH after MEDL. Methods  A urokinase-treated antithrombogenic drain, which is available only with a large diameter, was reduced in diameter and used after MEDL. Magnetic resonance imaging (MRI) and computed tomography (CT) were performed 36 to 48 hours after surgery. The size of the SEH was measured by MRI, and the location of the drain tip was assessed by CT scan. After imaging, the drain was removed. Results Use of the urokinase-treated antithrombogenic drain reduced the incidence of SEH. However, the drain was not adequately placed in many cases, limiting the effect of the drainage. When the urokinase-treated antithrombogenic drain was placed contralaterally to the approach side using an unsheathed endoscope, the incidence of SEH was further reduced. Conclusions The urokinase-treated antithrombogenic drain prevented thrombus-related drain obstruction. In addition, unsheathed endoscopic contralateral placement of the drain was effective for SEH prevention. PMID:26935298

  2. Soluble urokinase plasminogen activation receptor - An emerging new biomarker of cardiovascular disease and critical illness

    PubMed Central

    Cyrille, Nicole B.; Villablanca, Pedro A.; Ramakrishna, Harish

    2016-01-01

    Soluble urokinase plasminogen activation receptor (suPAR) is an emerging new biomarker, which has been shown to not only correlate with traditional biomarkers but also outperform CRP at prognosticating CVD. More clinical trials on suPAR is in the future research agenda. PMID:27052059

  3. Abnormal thallium 201 scintigraphy during low-dose vasopressin infusions

    SciTech Connect

    Davison, R.; Kaplan, K.; Bines, A.; Spies, S.; Reed, M.T.; Lesch, M.

    1986-12-01

    Thallium 201 (/sup 201/Tl) myocardial scans were obtained in 16 patients just prior to the discontinuation of a vasopressin infusion (.1 to .2 units/min) administered for the treatment of upper gastrointestinal bleeding. Repeat scintigraphy was performed two to three hours after the vasopressin was stopped. Eleven of the 16 patients (69 percent) demonstrated areas of decreased myocardial /sup 201/Tl uptake that resolved after the infusion was stopped. Heart rate-blood pressure product was significantly lower at the time of the second scan. Autopsies were secured in three of 11 scan-positive patients: one had severe coronary artery obstruction, one nonsignificant disease, and another had normal coronary arteries. Vasopressin, even at low doses, can induce abnormalities in myocardial perfusion that are probably mediated by a direct effect on the coronary circulation. They are usually not detectable by routine monitoring techniques and conceivably form the basis for the cardiovascular morbidity associated with the use of this agent.

  4. [Intra-arterial thrombolysis of a basilar vascular accident during coronary angiography].

    PubMed

    Battikh, K; Rihani, R; Lemahieu, J M; Mokahal, M; Houchaymi, Z; Cornaert, P; Dutoit, A

    2001-09-01

    The authors report the case of a 67 year old man with a previous history of aortobifemoral arterial graft who had unstable angina after carotid endarterectomy. Coronary angiography by the right brachial artery was complicated by a cerebrovascular accident with a reactive coma, convulsions and respiratory problems. Selective angiography of the right vertebral artery showed an image of occlusive thrombosis of the basilar artery. In view of the clinical state and angiographic appearances, the authors decided on immediate intra-arterial thrombolysis with Urokinase which dissolved the clot and reestablished flow in the basilar artery, the cerebellar and posterior cerebral arteries. The outcome was favourable with immediate and good recovery of consciousness and hospital discharge on the sixth day without neurological or radiological sequellae. Cerebrovascular accident is a rare and potentially serious complication of left heart catheterisation which requires immediate cerebral angiography to determine the mechanism and propose an appropriate therapeutic approach. PMID:11603067

  5. Arterial embolism

    MedlinePlus

    ... the artery (arterial bypass) to create a second source of blood supply Clot removal through a balloon catheter placed into the affected artery or through open surgery on the artery (embolectomy) Opening of the ...

  6. Suction Thrombectomy of Thrombotic Occlusion of the Subclavian Artery in a Case of Takayasu's Arteritis

    SciTech Connect

    Purkayastha, Sukalyan; Jayadevan, E.R.; Kapilamoorthy, T.R.; Gupta, A.K. E-mail: gupta@sctimst.ac.in

    2006-04-15

    Takayasu's arteritis, also known as pulseless disease, is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. Percutaneous removal of arterial thrombus with the use of several devices has been reported, with mixed results. We present a case of Takayasu's arteritis with thrombotic occlusion of the subclavian artery in which pulsed urokinase injection and suction thrombectomy were used to revascularize a threatened limb and to establish the sole arterial supply to the brain.

  7. Tissue Blood Flow During Remifentanil Infusion With Carbon Dioxide Loading.

    PubMed

    Kanbe, Hiroaki; Matsuura, Nobuyuki; Kasahara, Masataka; Ichinohe, Tatsuya

    2015-01-01

    The aim of this study was to investigate the effect of changes in end-tidal carbon dioxide tension (ETCO2) during remifentanil (Remi) infusion on oral tissue blood flow in rabbits. Eight male tracheotomized Japan White rabbits were anesthetized with sevoflurane under mechanical ventilation. The infusion rate of Remi was 0.4 μg/kg/min. Carbon dioxide was added to the inspired gas to change the inspired CO2 tension to prevent changes in the ventilating condition. Observed variables were systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), common carotid artery blood flow (CCBF), tongue mucosal blood flow (TBF), mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF). The CCBF, TBF, BBF, UBF, and LBF values were increased, while MBF was decreased, under hypercapnia, and vice versa. The BBF, UBF, and LBF values were increased, while the MBF value was decreased, under hypercapnia during Remi infusion, and vice versa. The BBF, MBF, UBF, and LBF values, but not the CCBF and TBF values, changed along with ETCO2 changes during Remi infusion. PMID:26061573

  8. [Development of smart infusion system].

    PubMed

    Li, Junyang

    2014-01-01

    The free care smart infusion system which has the function of liquid end alarm and automatic stopping has been designed. In addition, the system can send the alarm to the health care staff by Zigbee wireless network. Besides, the database of infusion information has been set up, it can be used for inquiry afterwards. PMID:24839846

  9. Removing the confusion about infusion.

    PubMed

    Bayne, C G

    1997-02-01

    There is more to infusion technology than simply connecting the "pump-du-jour" to the central line. The purpose of infusion technology, its safety products and four categories of devices-elastomeric, mechanical, gas and membrane-are discussed. PMID:9287736

  10. Adjacent central venous catheters can result in immediate aspiration of infused drugs during renal replacement therapy.

    PubMed

    Kam, K Y R; Mari, J M; Wigmore, T J

    2012-02-01

    Dual-lumen haemodiafiltration catheters enable continuous renal replacement therapy in the critically ill and are often co-located with central venous catheters used to infuse drugs. The extent to which infusions are immediately aspirated by an adjacent haemodiafiltration catheter remains unknown. A bench model was constructed to evaluate this effect. A central venous catheter and a haemodiafiltration catheter were inserted into a simulated central vein and flow generated using centrifugal pumps within the simulated vein and haemodiafiltration circuit. Ink was used as a visual tracer and creatinine solution as a quantifiable tracer. Tracers were completely aspirated by the haemodiafiltration catheter unless the infusion was at least 1 cm downstream to the arterial port. No tracer was aspirated from catheters infusing at least 2 cm downstream. Orientation of side ports did not affect tracer elimination. Co-location of central venous and haemodiafiltration catheters may lead to complete aspiration of infusions into the haemodiafilter with resultant drug under-dosing. PMID:22059378

  11. Effects of Intrarenal and Intravenous Infusion of the Phosphodiesterase 3 Inhibitor Milrinone on Renin Secretion

    NASA Technical Reports Server (NTRS)

    Kumagai, Kazuhiro; Reid, Ian A.

    1994-01-01

    We have reported that administration of the phosphodiesterase III inhibitor milrinone increases renin secretion in conscious rabbits. The aim of the present study was to determine if the increase in renin secretion results from a direct renal action of milrinone, or from an indirect extrarenal effect of the drug. This was accomplished by comparing the effects of intrarenal and intravenous infusion of graded doses of milrinone on plasma renin activity in unilaterally nephrectomized conscious rabbits. Milrinone was infused into the renal artery in doses of 0.01, 0.1 and 1.0 micro-g/kg/min, and intravenously in the same rabbits in doses of 0.01, 0.1, 1.0 and 10 micro-g/kg/min. Each dose was infused for 15 min. No intrarenal dose of milrinone altered plasma renin activity or arterial pressure, although at the highest dose, there was a small increase in heart rate. Intravenous infusion of milrinone at 1.0 micro-g/kg/min increased plasma renin activity to 176 +/- 55% of the control value (P less than 0.05). Heart rate increased but arterial pressure did not change. Intravenous infusion of milrinone at 1O micro-g/kg/min increased plasma renin activity to 386 +/- 193% of control in association with a decrease in arterial pressure and an increase in heart rate. These results confirm that milrinone increases renin secretion, and indicate that the stimulation is due to an extrarenal effect of the drug.

  12. Induction of Brain Microvascular Endothelial Cell Urokinase Expression by Cryptococcus neoformans Facilitates Blood-Brain Barrier Invasion

    PubMed Central

    Stie, Jamal; Fox, Deborah

    2012-01-01

    The invasive ability of the blood-borne fungal pathogen Cryptococcus neoformans can be enhanced through interactions with host plasma components, such as plasminogen. Previously we showed by in vitro studies that plasminogen coats the surface of C. neoformans and is converted to the active serine protease, plasmin, by host plasminogen activators. Viable, but not formaldehyde- or sodium azide-killed, cryptococcal strains undergo brain microvascular endothelial cell-dependent plasminogen-to-plasmin activation, which results in enhanced, plasmin-dependent cryptococcal invasion of primary bovine brain microvascular endothelial cells and fungal ability to degrade plasmin substrates. In the present work, brain microvascular endothelial cells cultured with viable, but not killed, cryptococcal strains led to significant increases in both urokinase mRNA transcription and cell-associated urokinase protein expression. Soluble urokinase was also detected in conditioned medium from brain microvascular endothelial cells cultured with viable, but not killed, C. neoformans. Exposure of plasminogen pre-coated viable C. neoformans to conditioned medium from strain-matched brain microvascular endothelial cell-fungal co-cultures resulted in plasminogen-to-plasmin activation and plasmin-dependent cryptococcal invasion. siRNA-mediated silencing of urokinase gene expression or the use of specific inhibitors of urokinase activity abrogated both plasminogen-to-plasmin activation on C. neoformans and cryptococcal-brain microvascular endothelial cell invasion. Our results suggest that pathogen exploitation of the host urokinase-plasmin(ogen) system may contribute to C. neoformans virulence during invasive cryptococcosis. PMID:23145170

  13. Intraosseous infusion in pediatric patients.

    PubMed

    Neal, C J; McKinley, D F

    1994-01-01

    In traumatically injured or medically unstable pediatric patients requiring resuscitation, gaining intravenous access often is frustrating for the physician and agonizing for the patient. Even when cardiopulmonary resuscitation is performed by trained professionals, cardiac arrests in children in the prehospital setting have a mortality of 79% to 100%. Immediate vascular access such as that obtained by intraosseous infusion improves survival. The intraosseous infusion technique uses the medullary cavity in the tibia as a "noncollapsible vein" for parenteral infusion. It is indicated in a child in shock or cardiac arrest when two attempts to access peripheral vasculature have failed or when more than 2 minutes have elapsed in the attempt to gain access. Epinephrine, bicarbonate, calcium, lidocaine, and volume expanders can be infused via the intraosseous route. Complications rarely occur. The technique described here is gaining acceptance in both prehospital and emergency department settings. PMID:8169160

  14. Proctoclysis: emergency rectal fluid infusion.

    PubMed

    Tremayne, Vincent

    This article describes the use and effectiveness of proctoclysis (rectal fluid infusion) in providing fluid resuscitation in the absence of intravenous access in rural and remote environments. PMID:19856644

  15. [Transitory hyperbilirubinemia and oxytocin infusion].

    PubMed

    Quoss, I

    1978-01-01

    Serum bilirubin levels at 5th day of life was compared between 100 mature newborns with oxytocin infusion to the mother during labour and 100 mature newborns without oxytocin. Newborns, whose mothers received more than 5 IU oxytocin had significant higher bilirubin values than the controll group without oxytocin and the cases with oxytocin administration under 5 U. Hyperbilirubinaemie was also present in babies after vacuum extraction and oxytocin infusion. PMID:645287

  16. Effect of urokinase on the proliferation of primary cultures of human prostatic cells

    SciTech Connect

    Kirchheimer, J.C.; Wojta, J.; Hienert, G.; Christ, G.; Heger, M.E.; Pflueger, H.B.; Binder, B.R.

    1987-11-01

    The effects of exogenously added urokinase type plasminogen activator, tissue type plasminogen activator, plasmin and thrombin on the proliferation of primary cultures of cells derived from prostatic hyperplasia or prostatic carcinomas were investigated by measuring the incorporation of /sup 3/H-thymidine into the cultures. Addition of urokinase type plasminogen activator (1.35 x 10(-9) M) or thrombin (10(-7) M) to the culture medium caused a two-fold increase of /sup 3/H-thymidine incorporation, regardless of the origin of the prostatic cells. Tissue type plasminogen activator did not alter the rate of /sup 3/H-thymidine incorporation, whereas plasmin caused a 25% decrease of /sup 3/H-thymidine incorporation in all cultures.

  17. Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia

    PubMed Central

    Drapkin, Paola T.; O’Riordan, Catherine R.; Yi, Su Min; Chiorini, John A.; Cardella, Jonathan; Zabner, Joseph; Welsh, Michael J.

    2000-01-01

    Developing gene therapy for cystic fibrosis has been hindered by limited binding and endocytosis of vectors by human airway epithelia. Here we show that the apical membrane of airway epithelia express the urokinase plasminogen activator receptor (uPAR). Urokinase plasminogen activator (uPA), or a 7-residue peptide derived from this protein (u7-peptide), bound the receptor and stimulated apical endocytosis. Both ligands enhanced gene transfer by nonspecifically bound adenovirus and adeno-associated virus vectors and by a modified adenovirus vector that had been coupled to the u7-peptide. These data provide the first evidence that targeting an apical receptor can circumvent the two most important barriers to gene transfer in airway epithelia. Thus, the uPA/uPAR system may offer significant advantages for delivering genes and other pharmaceuticals to airway epithelia. PMID:10712430

  18. Targeting the urokinase plasminogen activator receptor enhances gene transfer to human airway epithelia.

    PubMed

    Drapkin, P T; O'Riordan, C R; Yi, S M; Chiorini, J A; Cardella, J; Zabner, J; Welsh, M J

    2000-03-01

    Developing gene therapy for cystic fibrosis has been hindered by limited binding and endocytosis of vectors by human airway epithelia. Here we show that the apical membrane of airway epithelia express the urokinase plasminogen activator receptor (uPAR). Urokinase plasminogen activator (uPA), or a 7-residue peptide derived from this protein (u7-peptide), bound the receptor and stimulated apical endocytosis. Both ligands enhanced gene transfer by nonspecifically bound adenovirus and adeno-associated virus vectors and by a modified adenovirus vector that had been coupled to the u7-peptide. These data provide the first evidence that targeting an apical receptor can circumvent the two most important barriers to gene transfer in airway epithelia. Thus, the uPA/uPAR system may offer significant advantages for delivering genes and other pharmaceuticals to airway epithelia. PMID:10712430

  19. [Significance of urokinase and its inhibitors in the invasiveness and metastasing of malignant tumors].

    PubMed

    Halámková, J; Kiss, I; Tomášek, J; Pavlovský, Z; Tuček, S; Penka, M

    2012-02-01

    Fibrinolysis is process, which leads to the degradation of fibrin to fibrin monomers. Fibrinolysis helps to regulate hemostasis and prevents the creation of inappropriately large thrombus, which could reduce blood flow to the bloodstream. The main enzyme involved in fibrinolysis is plasmin. Tissue plasminogen activator (tPA) and urokinase (uPA) are agents converting plasminogen into active plasmin, together with urokinase receptor (uPAR) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) form plasminogen activator system (PAS) which is among others also part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumours. In contrast to tPA that is fundamental in fibrinolysis, uPA plays an essential role in tissue degradation as part of physiological and pathological processes. uPAR is a GPI (glycosylphosphatidylinositol)-anchored protein. The binding of uPA to uPAR results in activation of protein tyrosine kinase, protein kinase C and MAP kinase. At the same time, direct signalling pathway via Jak/STAT cascade utilising signalling transduction of Scr-like protein tyrosine kinase have also been described. uPAR expression is regulated by many growth factors, e.g. EGF, FGF-2 and HGF. It seems that individual PAS factors are involved in the process of rendering malignant tumors invasive. To what degree this influence is essential to specific malignancies, should be answered by further research. In the article the authors present a summary of findings about the interaction of fibrinolysis and tumor process, especially on the effects of urokinase and other activators and their inhibitors in metastasis of malignant tumors. The text contains information on the factors theirs introduction into practice is still the subject of numerous discussions, but in the future, individual PAS factors could play an important role in planning treatment strategies and also could become targets of targeted therapy. PMID

  20. Proteolytic regulation of epithelial sodium channels by urokinase plasminogen activator: cutting edge and cleavage sites.

    PubMed

    Ji, Hong-Long; Zhao, Runzhen; Komissarov, Andrey A; Chang, Yongchang; Liu, Yongfeng; Matthay, Michael A

    2015-02-27

    Plasminogen activator inhibitor 1 (PAI-1) level is extremely elevated in the edematous fluid of acutely injured lungs and pleurae. Elevated PAI-1 specifically inactivates pulmonary urokinase-type (uPA) and tissue-type plasminogen activators (tPA). We hypothesized that plasminogen activation and fibrinolysis may alter epithelial sodium channel (ENaC) activity, a key player in clearing edematous fluid. Two-chain urokinase (tcuPA) has been found to strongly stimulate heterologous human αβγ ENaC activity in a dose- and time-dependent manner. This activity of tcuPA was completely ablated by PAI-1. Furthermore, a mutation (S195A) of the active site of the enzyme also prevented ENaC activation. By comparison, three truncation mutants of the amino-terminal fragment of tcuPA still activated ENaC. uPA enzymatic activity was positively correlated with ENaC current amplitude prior to reaching the maximal level. In sharp contrast to uPA, neither single-chain tPA nor derivatives, including two-chain tPA and tenecteplase, affected ENaC activity. Furthermore, γ but not α subunit of ENaC was proteolytically cleaved at ((177)GR↓KR(180)) by tcuPA. In summary, the underlying mechanisms of urokinase-mediated activation of ENaC include release of self-inhibition, proteolysis of γ ENaC, incremental increase in opening rate, and activation of closed (electrically "silent") channels. This study for the first time demonstrates multifaceted mechanisms for uPA-mediated up-regulation of ENaC, which form the cellular and molecular rationale for the beneficial effects of urokinase in mitigating mortal pulmonary edema and pleural effusions. PMID:25555911

  1. Arterial stick

    MedlinePlus

    ... venous blood) mainly in its content of dissolved gases . Testing arterial blood shows the makeup of the ... arteries. Blood samples are mainly taken to measure gases in the arteries. Abnormal results may point to ...

  2. Structural Basis of Interaction Between Urokinase-type Plasminogen Activator and its Receptor

    SciTech Connect

    Barinka,C.; Parry, G.; Callahan, J.; Shaw, D.; Kuo, A.; Cines, B.; Mazar, A.; Lubkowski, J.

    2006-01-01

    Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 {angstrom}. We report the 1.9 {angstrom} crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding.

  3. Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion

    PubMed Central

    Limberg, Jacqueline K.; Kellawan, J. Mikhail; Harrell, John W.; Johansson, Rebecca E.; Eldridge, Marlowe W.; Proctor, Lester T.; Sebranek, Joshua J.

    2014-01-01

    We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise − rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion (r = −0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. PMID:25038148

  4. Regional blood flow during continuous low-dose endotoxin infusion

    SciTech Connect

    Fish, R.E.; Lang, C.H.; Spitzer, J.A.

    1986-01-01

    Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Cardiac output and regional blood flow were determined by the radiolabeled microsphere method after 6 and 30 hr of ET or saline infusion. Cardiac output (CO) of ET rats was not different from time-matched controls, whereas arterial pressure was 13% lower after 30 hr of infusion. After both 6 and 30 hr of ET, pancreatic blood flow and percentage of cardiac output were lower than in controls. Estimated portal venous flow was decreased at each time point, and an increased hepatic arterial flow (significant after 30 hr) resulted in an unchanged total hepatic blood flow. Blood flow to most other tissues, including epididymal fat, muscle, kidneys, adrenals, and gastrointestinal tract, was similar between treatments. Maintenance of blood flow to metabolically important tissues indicates that the previously reported alterations in in vitro cellular metabolism are not due to tissue hypoperfusion. Earlier observations of in vitro myocardial dysfunction, coexistent with the significant impairment in pancreatic flow, raise the possibility that release of a myocardial depressant factor occurs not only in profound shock but also under less severe conditions of sepsis and endotoxemia.

  5. Noninvasive monitoring of beta-adrenergic tone during isoproterenol infusions.

    PubMed

    Easley, R B; Rodbard, D

    1977-12-01

    Sphygmo-Recording is a simple, noninvasive technique for analysis of pulse wave contour and timing which has been used to evaluate the change in cardiac dynamics during isoproterenol infusion. The QKd interval, i.e., the time interval between the onset of the QRS complex and the onset of the Korotkoff sound at the brachial artery when the sphygomomanometer cuff is at diastolic pressure, is normally 205 +/- 15 msec. Continuous intravenous infusion of isoproterenol at 0.01, 0.02, and 0.03 microgram/kg/min into 12 euthyroid normotensive adult volunteers for 10-min intervals resulted in decreases of 55, 79, and 89 msec in QKd and increases of heart rate of 14, 27, and 43 beats/min, respectively. The corresponding changes in dP/dt, i.e., slope of the pulse wave upstroke at the brachial artery determined noninvasively from the same records, were 0.65, 1.47, and 2.26 mm Hg/msec. These results confirm previous studies which indicate that the chronotropic response of normal subjects to isoproterenol infusion is comparable to that previously reported in patients with the putative "hyperdynamic beta-adrenergic state." PMID:200395

  6. A theoretical alternative intraosseous infusion site in severely hypovolemic children

    PubMed Central

    van Schoor, Albert-Neels; Bosman, Marius C.

    2015-01-01

    Background Studies have shown that the venous system tends to collapse during hypovolemic shock. The use of the bone marrow space for infusions is an effective alternative, with the tibial insertion site being the norm. Objectives This study was conducted to determine a quick intraosseous infusion method that could be an alternative to the tibial route in neonates during emergency situations. Method A sample of 30 neonatal cadavers was dissected to explore a possible alternative to the tibial insertion site. The needle was inserted in the superolateral aspect of the humerus. The needle infusion site was then dissected to determine possible muscular and neurovascular damage that might occur during the administration of this procedure, with the greatest concern being the posterior circumflex humeral artery and axillary nerve exiting the quadrangular space. The distance of the needle insertion site was measured in relation to the soft tissue as well as to bony landmarks. Results The calculated 95% confidence interval shows that the needle can be safely inserted into the intraosseous tissue at the greater tubercle of the humerus 9.5 mm – 11.1 mm from the acromion. This is about a little finger’s width from the acromioclavicular joint. Conclusion Anatomically, the described site is suggested to offer a safe alternative access point for emergency infusion in severely hypovolemic newborns and infants, without the risk of damage to any anatomical structures. PMID:26245618

  7. The Angiotensin Infusion Test and Peripheral Venous Renin Activity

    PubMed Central

    Silah, J. G.; Strong, C. G.; Nowaczynski, W.; Genest, J.

    1967-01-01

    Forty hypertensive patients were studied to examine the assumption that the angiotensin pressor dose reflects endogenous renin activity. Peripheral renin activity was assayed by the method of Boucher et al.4 Sensitivity to the infusion of synthetic angiotensin II was determined as suggested by Kaplan and Silah.1 Sixteen patients with essential hypertension with normal renal angiography required 3.8 ng. angiotensin/kg./min. to raise the diastolic pressure 20 mm. Hg. All but one were sensitive to angiotensin infusion of less than 5 ng./kg./min. Renin activity was normal in all except in one sensitive subject. Angiotensin infusion response and mean renin activity in 13 patients with essential hypertension with abnormal renal angiography were similar to that of the first group. The pressor dose in 11 renovascular hypertensives was 9.8 ng./kg./min. All but three had elevated plasma renin activity. Our results suggest that: (1) the angiotensin infusion test is suitable for differentiating patients with true renovascular hypertension from those with essential hypertension with or without associated renal artery disease; (2) the angiotensin pressor dose correlates with the level of peripheral venous renin activity (p < 0.01). PMID:4290836

  8. The angiotensin infusion test and peripheral venous renin activity.

    PubMed

    Silah, J G; Strong, C G; Nowaczynski, W; Genest, J

    1967-05-27

    Forty hypertensive patients were studied to examine the assumption that the angiotensin pressor dose reflects endogenous renin activity. Peripheral renin activity was assayed by the method of Boucher et al.(4) Sensitivity to the infusion of synthetic angiotensin II was determined as suggested by Kaplan and Silah.(1)Sixteen patients with essential hypertension with normal renal angiography required 3.8 ng. angiotensin/kg./min. to raise the diastolic pressure 20 mm. Hg. All but one were sensitive to angiotensin infusion of less than 5 ng./kg./min. Renin activity was normal in all except in one sensitive subject. Angiotensin infusion response and mean renin activity in 13 patients with essential hypertension with abnormal renal angiography were similar to that of the first group. The pressor dose in 11 renovascular hypertensives was 9.8 ng./kg./min. All but three had elevated plasma renin activity.OUR RESULTS SUGGEST THAT: (1) the angiotensin infusion test is suitable for differentiating patients with true renovascular hypertension from those with essential hypertension with or without associated renal artery disease; (2) the angiotensin pressor dose correlates with the level of peripheral venous renin activity (p < 0.01). PMID:4290836

  9. Pulse-plethysmographic variables in hemodynamic assessment during mannitol infusion.

    PubMed

    Radhakrishnan, M; Mohanvelu, K; Veena, S; Sripathy, G; Umamaheswara Rao, G S

    2012-04-01

    Plethysmographic signal using pulse oximetry may be used to assess fluid status of patients during surgery as it resembles arterial pressure waveform. This will avoid placement of invasive arterial lines. This study was designed to find out whether intravascular volume changes induced by mannitol bolus in neurosurgical patients are detected by variations in arterial pressure and plethysmographic waveforms and also to assess the strength of correlation between different variables derived from these two waveforms. The time difference between the onset of arterial and plethysmographic waveforms as means of significant hemodynamic changes was also evaluated. Forty one adult ASA I and II neurosurgical patients requiring mannitol infusion were recruited. Arterial line and plethysmographic probe were placed in the same limb. Digitized waveforms were collected before, at the end, and 15, 30 and 60 min after mannitol infusion. Using MATLAB, the following parameters were collected for three consecutive respiratory cycles,-systolic pressure variation (SPV), pulse pressure variation (PPV), plethysmographic peak variation (Pl-PV), plethysmographic amplitude variation (Pl-AV) and blood pressure-plethysmographic time lag (BP-Pleth time lag). Changes in above parameters over the study period were studied using repeated measure analysis of variance. Correlation between the parameters was analysed. SPV and Pl-PV showed significant increase at 15, 30 and 60 min compared to end of mannitol infusion (P < 0.01 for SPV; P < 0.05 for Pl-PV). PPV and Pl-AV showed significant increase only at 30 min (P < 0.05). The correlation between ∆SPV-∆Pl-PV, ∆PPV-∆Pl-AV and ∆SPV-∆BP-Pleth time lag were significant (r = 0.3; P < 0.01). SPV and time lag had no significant interaction. Pl-PV correlates well with SPV following mannitol infusion and can be used as an alternative to SPV. (BP-Pleth) time-lag promises to be an important parameter in assessing the state of peripheral

  10. Transient severe brain stem depression during intraarterial papaverine infusion for cerebral vasospasm

    SciTech Connect

    Barr, J.D.; Mathis, J.M.; Horton, J.A. )

    1994-04-01

    A 63-yr-old woman had severe, symptomatic cerebral vasospasm secondary to subarachnoid hemorrhage. We initiated simultaneous infusions of papaverine into her left vertebral and left internal carotid arteries. Twenty-five minutes after the fusions had begun, the patient had a transient reaction of respiratory arrest followed by rapid, progressive loss of brain stem function. 28 refs., 1 fig.

  11. Effects of methacholine infusion on desflurane pharmacokinetics in piglets.

    PubMed

    Kozian, Alf; Kretzschmar, Moritz; Baumgardner, James E; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2015-12-01

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (V T)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and

  12. Effects of methacholine infusion on desflurane pharmacokinetics in piglets☆

    PubMed Central

    Kozian, Alf; Kretzschmar, Moritz; Baumgardner, James E.; Schreiber, Jens; Hedenstierna, Göran; Larsson, Anders; Hachenberg, Thomas; Schilling, Thomas

    2015-01-01

    The data of a corresponding animal experiment demonstrates that nebulized methacholine (MCh) induced severe bronchoconstriction and significant inhomogeneous ventilation and pulmonary perfusion (V̇A/Q̇) distribution in pigs, which is similar to findings in human asthma. The inhalation of MCh induced bronchoconstriction and delayed both uptake and elimination of desflurane (Kretzschmar et al., 2015) [1]. The objective of the present data is to determine V̇A/Q̇ matching by Multiple Inert Gas Elimination Technique (MIGET) in piglets before and during methacholine- (MCh-) induced bronchoconstriction, induced by MCh infusion, and to assess the blood concentration profiles for desflurane (DES) by Micropore Membrane Inlet Mass Spectrometry (MMIMS). Healthy piglets (n=4) under general anesthesia were instrumented with arterial, central venous, and pulmonary artery lines. The airway was secured via median tracheostomy with an endotracheal tube, and animals were mechanically ventilated with intermittent positive pressure ventilation (IPPV) with a FiO2 of 0.4, tidal volume (VT)=10 ml/kg and PEEP of 5cmH2O using an open system. The determination of V.A/Q. was done by MIGET: before desflurane application and at plateau in both healthy state and during MCh infusion. Arterial blood was sampled at 0, 1, 2, 5, 10, 20, and 30 min during wash-in and washout, respectively. Bronchoconstriction was established by MCH infusion aiming at doubling the peak airway pressure, after which wash-in and washout of the anesthetic gas was repeated. Anesthesia gas concentrations were measured by MMIMS. Data were analyzed by ANOVA, paired t-test, and by nonparametric Friedman׳s test and Wilcoxon׳s matched pairs test. We measured airway pressures, pulmonary resistance, and mean paO2 as well as hemodynamic variables in all pigs before desflurane application and at plateau in both healthy state and during methacholine administration by infusion. By MIGET, fractional alveolar ventilation and

  13. Infusing Culture in Career Counseling

    ERIC Educational Resources Information Center

    Arthur, Nancy; Collins, Sandra

    2011-01-01

    This article introduces the culture-infused career counselling (CICC) model. Six principles are foundational to a tripartite model emphasizing cultural self-awareness, awareness of client cultural identities, and development of a culturally sensitive working alliance. The core competencies ensure the cultural validity and relevance of career…

  14. Infusing Service Learning into Instruction.

    ERIC Educational Resources Information Center

    Arrington, Harriette J.; Moore, Sara Delano

    2001-01-01

    Describes how service learning can link to the middle school curriculum to strengthen the learning of various skills and concepts. Presents service learning model involving preparation, action, reflection, and recognition. Includes examples of effective infusion of service learning into units, lessons, and projects. Concludes with recommendations…

  15. Enhancing Instruction through Software Infusion.

    ERIC Educational Resources Information Center

    Sia, Archie P.

    The presence of the computer in the classroom is no longer considered an oddity; it has become an ordinary resource for teachers to use for the enhancement of instruction. This paper presents an examination of software infusion, i.e., the use of computer software to enrich instruction in an academic curriculum. The process occurs when a chosen…

  16. Effects of bacteria involved with the pathogenesis of infection-induced urolithiasis on the urokinase and sialidase (neuraminidase) activity.

    PubMed

    du Toit, P J; van Aswegen, C H; Steyn, P L; Pols, A; du Plessis, D J

    1992-01-01

    It has been hypothesized that urinary urokinase and sialidase may play a role in urolithiasis. If these theories have substance it is to be expected that microorganisms may also affect these enzymes, since the association between urinary tract infection and renal stone formation is well known. It is generally assumed that Proteus mirabilis and Staphylococcus albus, which produce the urea-splitting enzyme urease, are responsible for stone formation. However, the importance of non-urease-producing microorganisms (Escherichia coli and Enterococcus) in urolithiasis is unclear. Spectrophotometric studies were therefore devised to clarify this problem. Microorganisms associated with infection-induced stones (Proteus mirabilis and Escherichia coli) respectively inhibited the urokinase and stimulated the sialidase activity. In contrast, microorganisms which were not associated with infection stones (Bacillus subtilis) had significantly less effect on urokinase and sialidase activity. This study may explain infection-induced stone formation and could open a completely new line of research. PMID:1462476

  17. Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro

    PubMed Central

    Wilson, A; Gibson, P

    2000-01-01

    BACKGROUND—Migration of colonic epithelial cells is important for mucosal repair following injury. The urokinase (u-PA) system regulates migration in other cell types.
AIM—To examine the role of u-PA and its receptor (u-PAR) in colonic epithelial cell migration.
METHODS—Migration was assessed over 24 hours in circular wounds made in confluent monolayers of LIM1215 and Caco-2 human colon cancer cells. The function of u-PA and u-PAR was ablated with antisense oligonucleotides to block expression, with synthetic u-PA peptides to block interaction, and with aprotinin to block u-PA mediated proteolysis.
RESULTS—Migration was stimulated two to threefold by exogenous u-PA, an effect dependent on u-PAR binding but independent of u-PA mediated mitogenesis and proteolysis. Expression of u-PA and u-PAR was inhibited by 80% by the appropriate antisense oligonucleotide. Basal migration and the motogenic effects of butyrate, epidermal growth factor, and phorbol-12-myristate-13-acetate were suppressed by the u-PAR antisense oligonucleotide (40-60%) but were at best minimally affected following inhibition of u-PA expression and binding. 
CONCLUSIONS—In an in vitro model of wounded colonic epithelium, u-PAR promotes cell migration through mechanisms that are not exclusively dependent on u-PA binding. Therefore, u-PA and u-PAR may contribute to colonic mucosal repair in vivo.


Keywords: colon; migration; urokinase; urokinase receptor; epidermal growth factor; butyrate; protein kinase C PMID:10861271

  18. Emergency Coronary Artery Bypass Graft Surgery for Iatrogenic Left Main Coronary Artery Dissection

    PubMed Central

    Tarbiat, Masoud; Safarpoor, Gholamreza

    2015-01-01

    Iatrogenic coronary artery dissection during coronary angiography with or without rupture is a rare but feared complication. We herein report a case of iatrogenic left main coronary artery dissection in a 49-year-old female. Admitted to our hospital with a recent history of severe hypotension, she develpled apnea during angiography. She was intubated and resuscitated with an Epinephrine infusion in the Cath-Lab. The diagnosis was iatrogenic left main coronary artery dissection based on angiography. Immediately, the patient was transferred to the operating room in a lethargic state with an Epinephrine infusion and prepared for emergency coronary artery bypass graft surgery. In the ICU, she was completely alert with no hemodynamic complications and finally was discharged in a good overall condition. At 18 months' follow-up, the patient was in a stable situation with good daily function. PMID:26985212

  19. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and... Infusion pump. (a) Identification. An infusion pump is a device used in a health care facility to pump fluids into a patient in a controlled manner. The device may use a piston pump, a roller pump, or...

  20. Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

    SciTech Connect

    Yang, Shuofei Liu, Baochen Ding, Weiwei He, Changsheng Wu, Xingjiang Li, Jieshou

    2015-02-15

    PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.

  1. Cardiopulmonary effects of an intravenous infusion of guaifenesin, ketamine, and xylazine in dogs.

    PubMed

    Benson, G J; Thurmon, J C; Tranquilli, W J; Smith, C W

    1985-09-01

    A 5% solution of dextrose in water containing 50 mg of guaifenesin, 0.25 mg of xylazine, and 1 mg of ketamine/ml was infused IV at the rate of 2.2 ml X kg-1 X hour-1 in dogs. Heart rate, systemic vascular resistance, mean arterial blood pressure, rate-pressure product, and arterial oxygen tension were not altered significantly from baseline values during 2 hours of anesthesia. Cardiac index was significantly (P less than 0.05) decreased from base-line values. Hypoventilation resulted in increased arterial carbon dioxide tension and decreased arterial pH. After the dogs were given glycopyrrolate, cardiac index returned to base line, and heart rate, mean arterial pressure, and rate-pressure product were significantly greater (P less than 0.05) than base-line values. PMID:3931517

  2. Pulmonary vascular resistance during lipid infusion in neonates.

    PubMed Central

    Prasertsom, W.; Phillipos, E. Z.; Van Aerde, J. E.; Robertson, M.

    1996-01-01

    Using two-dimensional echocardiography, pulmonary vascular resistance was estimated from right ventricular pre-ejection period to ejection time (RVPEP/ET) in 11 preterm infants with respiratory distress, to test the effect of different doses of continuous lipid infusion. Echocardiography was performed at baseline with no lipid infusing 2 and 24 hours after 1.5 and 3 g/kg/day of intravenous lipid, 24 hours after discontinuing intravenous lipid emulsion, and 2 hours after restarting intravenous lipid. After 24 hours of intravenous lipid at 1.5 g/kg/day the RVPEP/ET rose to mean (SD) 0.287 (0.03) from a baseline value of 0.225 (0.02) and to 0.326 (0.05) after 24 hours of intravenous lipid at 3 g/kg/day. Pulmonary arterial pressure returned to baseline 24 hours after the intravenous lipid had been discontinued. Continuous 24 hour infusion of lipid caused significant dose and time-dependent increases in pulmonary vascular resistance. Intravenous lipid may aggravate pulmonary hypertension. PMID:8777674

  3. Isolated limb infusion chemotherapy with or without hemofiltration for recurrent limb melanoma

    PubMed Central

    Cecchini, Sara; Sarti, Donatella; Ricci, Stefano; Vergini, Ludovico Delle; Sallei, Manuela; Serresi, Stefano; Ricotti, Giuseppe; Mulazzani, Luca; Lattanzio, Fabrizia; Fiorentini, Giammaria

    2015-01-01

    AIM: To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma. METHODS: Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity, > 18 years, performances status (Eastern Cooperative Oncology Group ) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion (ILI)], and to stop the out flow (venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration (HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug. RESULTS: Thirty seven ILI were done in 29 cases (31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients (38%) received infusion of melphalan alone, 7 (24%) melphalan associated to mitomicin C and 7 (24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients (10%) were complete responders and 16 (56%) were partial responders; whereas 7 patients (24%) had stable disease, and 3 (10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade (I and II) toxicity. CONCLUSION: ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable

  4. The Heparin-Induced Thrombocytopenia and Thrombosis Syndrome: Treatment with Intraarterial Urokinase and Systemic Platelet Aggregation Inhibitors

    SciTech Connect

    Murphy, Kenneth D.; McCrohan, Gerard; DeMarta, Deborah A.; Shirodkar, Nitin B.; Kwon, Oun J.; Chopra, Paramjit S.

    1996-03-15

    We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin.

  5. Acute arterial occlusion - kidney

    MedlinePlus

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...

  6. Acute arterial occlusion - kidney

    MedlinePlus

    ... arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury ...

  7. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  8. Renovascular remodeling and renal injury after extended angiotensin II infusion.

    PubMed

    Casare, Fernando Augusto Malavazzi; Thieme, Karina; Costa-Pessoa, Juliana Martins; Rossoni, Luciana Venturini; Couto, Gisele Kruger; Fernandes, Fernanda Barrinha; Casarini, Dulce Elena; Oliveira-Souza, Maria

    2016-06-01

    Chronic angiotensin II (ANG II) infusion for 1 or 2 wk leads to progressive hypertension and induces inward hypertrophic remodeling in preglomerular vessels, which is associated with increased renal vascular resistance (RVR) and decreased glomerular perfusion. Considering the ability of preglomerular vessels to exhibit adaptive responses, the present study was performed to evaluate glomerular perfusion and renal function after 6 wk of ANG II infusion. To address this study, male Wistar rats were submitted to sham surgery (control) or osmotic minipump insertion (ANG II 200 ng·kg(-1)·min(-1), 42 days). A group of animals was treated or cotreated with losartan (10 mg·kg(-1)·day(-1)), an AT1 receptor antagonist, between days 28 and 42 Chronic ANG II infusion increased systolic blood pressure to 185 ± 4 compared with 108 ± 2 mmHg in control rats. Concomitantly, ANG II-induced hypertension increased intrarenal ANG II level and consequently, preglomerular and glomerular injury. Under this condition, ANG II enhanced the total renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow and induced pressure natriuresis. These changes were accompanied by lower RVR and enlargement of the lumen of interlobular arteries and afferent arterioles, consistent with impairment of renal autoregulatory capability and outward preglomerular remodeling. The glomerular injury culminated with podocyte effacement, albuminuria, tubulointerstitial macrophage infiltration and intrarenal extracellular matrix accumulation. Losartan attenuated most of the effects of ANG II. Our findings provide new information regarding the contribution of ANG II infusion over 2 wk to renal hemodynamics and function via the AT1 receptor. PMID:26962104

  9. Continuous Intra-Arterial Nimodipine for the Treatment of Cerebral Vasospasm

    SciTech Connect

    Mayer, Thomas E.; Dichgans, Martin; Straube, Andreas; Birnbaum, Tobias; Mueller-Schunk, Stephanie; Hamann, Gerhard F.; Schulte-Altedorneburg, Gernot

    2008-11-15

    Two patients with refractory symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) were treated by continuous intra-arterial nimodipine infusion via a catheter placed in the internal carotid artery or vertebral artery for 3 and 12 days, respectively. Recovery of the neurological deficits, normalization of MR perfusion, a decrease in the elevated mean flow velocity measured by transcranial duplex sonography, and angiographic recanalization were observed. Continuous intra-arterial nimodipine might be a treatment option in severe refractory vasospasm following SAH.

  10. The Safety of Target-Controlled Infusions.

    PubMed

    Schnider, Thomas W; Minto, Charles F; Struys, Michel M R F; Absalom, Anthony R

    2016-01-01

    Target-controlled infusion (TCI) technology has been available in most countries worldwide for clinical use in anesthesia for approximately 2 decades. This infusion mode uses pharmacokinetic models to calculate infusion rates necessary to reach and maintain the desired drug concentration. TCI is computationally more complex than traditional modes of drug administration. The primary difference between TCI and conventional infusions is that TCI decreases the infusion rate at regular intervals to account for the uptake of drug into saturable compartments. Although the calculated infusion rates are consistent with manually controlled infusion rates, there are concerns that TCI administration of IV anesthetics could introduce unique safety concerns. After approximately 2 decades of clinical use, it is appropriate to assess the safety of TCI. Our aim in this article was to describe safety-relevant issues related to TCI, which should have emerged after its use in millions of patients. We collected information from published medical literature, TCI manufacturers, and publicly available governmental Web sites to find evidence of safety issues with the clinical use of TCI. Although many case reports emphasize that IV anesthesia is technically more demanding than inhaled anesthesia, including human errors associated with setting up IV infusions, no data suggest that a TCI mode of drug delivery introduces unique safety issues other than selecting the wrong pharmacokinetic model. This is analogous to the risk of selecting the wrong drug with current infusion pumps. We found no evidence that TCI is not at least as safe as anesthetic administration using constant rate infusions. PMID:26516801

  11. Cardiovascular effects of dobutamine and phenylephrine infusion in sevoflurane-anesthetized Thoroughbred horses.

    PubMed

    Ohta, Minoru; Kurimoto, Shinjiro; Ishikawa, Yuhiro; Tokushige, Hirotaka; Mae, Naomi; Nagata, Shun-ichi; Mamada, Masayuki

    2013-11-01

    To determine dose-dependent cardiovascular effects of dobutamine and phenylephrine during anesthesia in horses, increasing doses of dobutamine and phenylephrine were infused to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and infused 3 increasing doses of dobutamine (0.5, 1.0 and 2.0 µg/kg/min) for 15 min each dose. Following to 30 min of reversal period, 3 increasing doses of phenylephrine (0.25, 0.5 and 1.0 µg/kg/min) were infused. Cardiovascular parameters were measured before and at the end of each 15-min infusion period for each drug. Blood samples were collected every 5 min during phenylephrine infusion period. There were no significant changes in heart rate throughout the infusion period. Both dobutamine and phenylephrine reversed sevoflurane-induced hypotension. Dobutamine increased both mean arterial blood pressure (MAP) and cardiac output (CO) as the result of the increase in stroke volume, whereas phenylephrine increased MAP but decreased CO as the result of the increase in systemic vascular resistance. Plasma phenylephrine concentration increased dose-dependently, and these values at 15, 30 and 45 min were 6.2 ± 1.2, 17.0 ± 4.8 and 37.9 ± 7.3 ng/ml, respectively. PMID:23832627

  12. Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock

    SciTech Connect

    Ognibene, F.P.; Parker, M.M.; Natanson, C.; Shelhamer, J.H.; Parrillo, J.E.

    1988-05-01

    Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was a strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock.

  13. Bound plasminogen is rate-limiting for cell-surface-mediated activation of plasminogen by urokinase.

    PubMed Central

    Namiranian, S; Naito, Y; Kakkar, V V; Scully, M F

    1995-01-01

    The ability of U937 monocyte-like cells and KATO III cells (a human gastric carcinoma line) to potentiate activation of plasminogen by single-chain urokinase-type plasminogen activator (scu-PA), as mediated by the cell receptor for urokinase (u-PAR), was compared. It was observed that, although the concentration of u-PAR on these cell lines differed considerably (U937 cells: 5000 receptors/cell, Kd 0.35 nM; KATO III cells: 400 receptors/cell, Kd 0.85 nM), the rate of activation of plasminogen by scu-PA in the presence of the same density of each cell line was equivalent. From data generated in the presence of increasing concentrations of scu-PA, the kcat, for plasminogen activation in the presence of each cell line was calculated and found to differ by 26-fold (0.36 s-1 on U937 cells; 9.25 s-1 on KATO III cells). However, the Km for plasminogen with respect to the rate of formation of plasmin was lower than the Kd for binding (0.2 microM compared with 0.5 microM on U937 cells; 0.34 microM compared with 1.6 microM on KATO III cells). A rapid transformation from Glu-plasminogen (native plasminogen with N-terminal Glu) to Lys-plasminogen (plasmin-degraded plasminogen with primarily N-terminal Lys-77) occurred on the surface of U937 cells (unlike KATO III cells), but this transition did not coincide with faster rates of plasminogen activation. From this evidence it is concluded that the accessibility of bound plasminogen acts to limit the rate of activation by cell-bound urokinase. The significance of this proposal is that the proteolytic potential of the cell-mediated activation of plasminogen would be controlled by the accessibility of plasminogen for activation rather than by the concentration of u-PAR (the latter may act to localize proteolysis to appropriate domains on the surface of the cell). PMID:7639718

  14. Arterial stick

    MedlinePlus

    ... limit tissue damage. Alternative Names Blood sample - arterial ... by: Linda J. Vorvick, MD, Medical Director and Director of Didactic Curriculum, MEDEX Northwest Division of Physician Assistant Studies, ...

  15. Arterial Catheterization

    MedlinePlus

    ... rial line can provide valuable information to adjust oxygen therapy or mechanical ventilator (respirator; breathing machine) settings. The blood oxygen pres- sure measures from an arterial line give ...

  16. Infusing PDA technology into nursing education.

    PubMed

    White, Ann; Allen, Patricia; Goodwin, Linda; Breckinridge, Daya; Dowell, Jeffery; Garvy, Ryan

    2005-01-01

    Use of the personal digital assistant (PDA) has been infused into the accelerated baccalaureate program at Duke University to help prepare nursing students for professional practice. The authors provide an overview of the use of PDAs in the classroom, laboratory, and clinical setting. Technical aspects of PDA infusion and steps to ensure regulatory compliance are explored. Benefits of PDA use by both faculty and students in the program and challenges met with the infusion of this technology are also described. PMID:16030450

  17. Design of low cost smart infusion device

    NASA Astrophysics Data System (ADS)

    Saputra, Yohanes David; Purnamaningsih, Retno Wigajatri

    2015-01-01

    We propose design of a smart infusion device suitable for public hospitals in Indonesia. The device comprised of LED, photodiode and DC motor to measure and control the infusion rate, using the principle of LED beam absorption. The infusion rate was identified by using microcontroller and displayed through computer unit. Experiment results for different flow rate level and concentration of Dextrose showed that the device is able to detect, measure, and control the infusion droplets flow rate by the average error rate of 1.0081%.

  18. Overexpression of urokinase-type plasminogen activator in transgenic mice is correlated with impaired learning.

    PubMed Central

    Meiri, N; Masos, T; Rosenblum, K; Miskin, R; Dudai, Y

    1994-01-01

    Transgenic mice designated alpha MUPA overproduce in the brain murine urokinase-type plasminogen activator (uPA), an extracellular protease implicated in tissue remodeling. We have now localized, by in situ hybridization, extensive signal of uPA mRNA in the alpha MUPA cortex, hippocampus, and amygdala, sites that were not labeled in counterpart wild-type mice. Furthermore, biochemical measurements reveal a remarkably high level of enzymatic activity of uPA in the cortex and hippocampus of alpha MUPA compared with wild-type mice. We have used the alpha MUPA mice to examine whether the abnormal level of uPA in the cortex and the limbic system affects learning ability. We report that alpha MUPA mice perform poorly in tasks of spatial, olfactory, and taste-aversion learning, while displaying normal sensory and motor capabilities. Our results suggest that uPA is involved in neural processes subserving a variety of learning types. Images PMID:8159723

  19. Ligand Binding Alters Dimerization and Sequestering of Urokinase Receptors in Raft-Mimicking Lipid Mixtures

    PubMed Central

    Ge, Yifan; Siegel, Amanda P.; Jordan, Rainer; Naumann, Christoph A.

    2014-01-01

    Lipid heterogeneities, such as lipid rafts, are widely considered to be important for the sequestering of membrane proteins in plasma membranes, thereby influencing membrane protein functionality. However, the underlying mechanisms of such sequestration processes remain elusive, in part, due to the small size and often transient nature of these functional membrane heterogeneities in cellular membranes. To overcome these challenges, here we report the sequestration behavior of urokinase receptor (uPAR), a glycosylphosphatidylinositol-anchored protein, in a planar model membrane platform with raft-mimicking lipid mixtures of well-defined compositions using a powerful optical imaging platform consisting of confocal spectroscopy XY-scans, photon counting histogram, and fluorescence correlation spectroscopy analyses. This methodology provides parallel information about receptor sequestration, oligomerization state, and lateral mobility with single molecule sensitivity. Most notably, our experiments demonstrate that moderate changes in uPAR sequestration are not only associated with modifications in uPAR dimerization levels, but may also be linked to ligand-mediated allosteric changes of these membrane receptors. Our data show that these modifications in uPAR sequestration can be induced by exposure to specific ligands (urokinase plasminogen activator, vitronectin), but not via adjustment of the cholesterol level in the planar model membrane system. Good agreement of our key findings with published results on cell membranes confirms the validity of our model membrane approach. We hypothesize that the observed mechanism of receptor translocation in the presence of raft-mimicking lipid mixtures is also applicable to other glycosylphosphatidylinositol-anchored proteins. PMID:25418095

  20. Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect.

    PubMed Central

    Resnati, M; Guttinger, M; Valcamonica, S; Sidenius, N; Blasi, F; Fazioli, F

    1996-01-01

    Physiological concentrations of urokinase plasminogen activator (uPA) stimulated a chemotactic response in human monocytic THP-1 through binding to the urokinase receptor (uPAR). The effect did not require the protease moiety of uPA, as stimulation was achieved also with the N-terminal fragment (ATF), while the 33 kDa low molecular weight uPA was ineffective. Co-immunoprecipitation experiments showed association of uPAR with intracellular kinase(s), as demonstrated by in vitro kinase assays. Use of specific antibodies identified p56/p59hck as a kinase associated with uPAR in THP-1 cell extracts. Upon addition of ATF, p56/p59hck activity was stimulated within 2 min and returned to normal after 30 min. Since uPAR lacks an intracellular domain capable of interacting with intracellular kinase, activation of p56/p59hck must require a transmembrane adaptor. Evidence for this was strongly supported by the finding that a soluble form of uPAR (suPAR) was capable of inducing chemotaxis not only in THP-1 cells but also in cells lacking endogenous uPAR (IC50, 5 pM). However, activity of suPAR require chymotrypsin cleavage between the N-terminal domain D1 and D2 + D3. Chymotrypsin-cleaved suPAR also induced activation of p56/p59hck in THP-1 cells, with a time course comparable with ATF. Our data show that uPA-induced signal transduction takes place via uPAR, involves activation of intracellular tyrosine kinase(s) and requires an as yet undefined adaptor capable of connecting the extracellular ligand binding uPAR to intracellular transducer(s). Images PMID:8612581

  1. Purification of rabbit kidney cytokinase and a comparison of its properties with human urokinase

    PubMed Central

    Ali, S. Y.; Evans, Lois

    1968-01-01

    1. The cytokinase (tissue activator of plasminogen) content of several mammalian tissues was evaluated by a quantitative casein hydrolysis method. 2. An alkaline (pH10·5) extraction of cytokinase from rabbit kidney lysosome–microsome fraction, followed by chromatography on DEAE-cellulose at pH7·6 with stepwise or linear increase in concentration of phosphate buffer, gave an 86-fold purification of the enzyme. The purified material was non-proteolytic against casein and heated fibrin and was freeze-dried without significant loss of activity or solubility. 3. Cytokinase is a protein with E0·1%1cm.=0·87 at 280mμ, and does not possess sufficient hexose or sialic acid to be classified as a glycoprotein. It has S20,w 2·9–3·1s and molecular weight 50000 when measured on a calibrated Sephadex G-100 column. It has an isoelectric point between pH8 and pH9, and is maximally active and stable at pH8·5. It is inactivated by heat at 78°. 4. Cytokinase and human urokinase have the same Km value and are inhibited in a partially competitive manner by ∈-aminohexanoic acid and aminomethylcyclohexanecarboxylic acid. They are also inhibited by cysteine and arginine, but are unaffected by iodoacetamide and p-chloromercuribenzoate. 5. On the basis of this and other evidence it is suggested that rabbit kidney cytokinase and human urokinase are similar, if not identical, enzymes. PMID:5641883

  2. Urokinase Receptors Promote β1 Integrin Function through Interactions with Integrin α3β1

    PubMed Central

    Wei, Ying; Eble, Johannes A.; Wang, Zemin; Kreidberg, Jordan A.; Chapman, Harold A.

    2001-01-01

    The urokinase receptor (uPAR) is linked to cellular migration through its capacity to promote pericellular proteolysis, regulate integrin function, and mediate cell signaling in response to urokinase (uPA) binding. The mechanisms for these activities remain incompletely defined, although uPAR was recently identified as a cis-acting ligand for the β2 integrin CD11b/CD18 (Mac-1). Here we show that a major β1 integrin partner for uPAR/uPA signaling is α3. In uPAR-transfected 293 cells uPAR complexed (>90%) with α3β1 and antibodies to α3 blocked uPAR-dependent vitronectin (Vn) adhesion. Soluble uPAR bound to recombinant α3β1 in a uPA-dependent manner (Kd < 20 nM) and binding was blocked by a 17-mer α3β1 integrin peptide (α325) homologous to the CD11b uPAR-binding site. uPAR colocalized with α3β1 in MDA-MB-231 cells and uPA (1 nM) enhanced spreading and focal adhesion kinase phosphorylation on fibronectin (Fn) or collagen type I (Col) in a pertussis toxin- and α325-sensitive manner. A critical role of α3β1 in uPA signaling was verified by studies of epithelial cells from α3-deficient mice. Thus, uPAR preferentially complexes with α3β1, promoting direct (Vn) and indirect (Fn, Col) pathways of cell adhesion, the latter a heterotrimeric G protein-dependent mechanism of signaling between α3β1 and other β1 integrins. PMID:11598185

  3. Conformation of one- and two-chain high molecular weight urokinase analyzed by small-angle neutron scattering and vacuum ultraviolet circular dichroism

    SciTech Connect

    Mangel, W.F.; Lin, B.H.; Ramakrishnan, V. )

    1991-05-25

    The structures of one- and two-chain high molecular weight human urokinase were analyzed by small-angle neutron scattering and vacuum ultraviolet circular dichroism. Both one- and two-chain high molecular weight urokinases exhibited a radius of gyration of 31 A and a maximum dimension of 90 A. Neither parameter was affected by the presence of lysine sufficient to saturate all the lysine-binding sites in human plasminogen. These physical parameters are consistent with the sedimentation coefficient of high molecular weight urokinase and indicate that both proteins are highly asymmetric. Neither protein contained much alpha-helix or parallel beta-sheet. Most of the secondary structure was in the form of antiparallel beta-sheet and beta-turns, very similar to the secondary structure of plasminogen. The macroscopic kinetic constants, Km and kcat, for the hydrolysis of (pyroGlu-Gly-Arg-NH)2-rhodamine by two-chain high molecular weight urokinase and low molecular weight urokinase which lacks the epidermal growth factor and kringle domains were similar. These structural and kinetic data are consistent with the domains in both forms of urokinase being independent structural and functional units.

  4. Intraarterial Infusion Therapy via a Subcutaneous Port for Limb-Threatening Ischemia: A Pilot Study

    SciTech Connect

    Strecker, Ernst-Peter K.; Ostheim-Dzerowycz, Wladimir; Boos, Irene B.L.

    1998-03-15

    Purpose: To present the initial results of a new percutaneously implantable catheter port system (PIPS) used for long-term intraarterial infusion therapy in patients with severe ischemic limb disease. Methods: Ten patients with deep, extended ischemic ulcerations (all 10) and osteomyelitis (6/10) of the foot received intraarterial infusions of prostaglandine E{sub 1} and antibiotics, if indicated, via a new port catheter system with the port placed subcutaneously above the groin after percutaneous introduction and the catheter tip placed into the superficial or deep femoral artery. Results: Port implantation and repeated port access were uncomplicated. During the follow-up period (mean 11 months, range 1 week-50 months), port migration, leakage, or infection was not observed. Three catheters thrombosed and were opened by fibrinolysis with recombinant tissue plasminogen activator instilled via the port. Treatment success was achieved in 8 patients: relief from rest pain (8 patients), reduction of ulcer size (4/8), and complete healing (4/8). Limb savage rate was 80%. In 2 patients amputation could not be avoided. Conclusion: Selective long-term arterial infusion therapy presents a valuable therapeutic regimen for limb salvage. With the new catheter port system, repeated local intraarterial infusion is safe and simple.

  5. Acute hepatitis after amiodarone infusion

    PubMed Central

    Fonseca, Paulo; Dias, Adelaide; Gonçalves, Helena; Albuquerque, Aníbal; Gama, Vasco

    2015-01-01

    Acute hepatitis is a very rare, but potentially fatal, adverse effect of intravenous amiodarone. We present a case of an 88-year-old man with history of ischemic dilated cardiomyopathy and severely depressed left ventricular function that was admitted to our coronary care unit with diagnosis of decompensated heart failure and non-sustained ventricular tachycardia. A few hours after the beginning of intravenous amiodarone he developed an acute hepatitis. There was a completely recovery within the next days after amiodarone withdrawn and other causes of acute hepatitis have been ruled out. This case highlights the need for close monitoring of hepatic function during amiodarone infusion in order to identify any potential hepatotoxicity and prevent a fatal outcome. Oral amiodarone is, apparently, a safe option in these patients. PMID:26488027

  6. Angioplasty and stent placement -- peripheral arteries

    MedlinePlus

    Percutaneous transluminal angioplasty - peripheral artery; PTA - peripheral artery; Angioplasty - peripheral arteries; Iliac artery -angioplasty; Femoral artery - angioplasty; Popliteal artery - angioplasty; Tibial artery - angioplasty; Peroneal artery - ...

  7. Infusing Systems Thinking into Career Counseling

    ERIC Educational Resources Information Center

    Ryan, Charles W.; Tomlin, James H.

    2010-01-01

    This study examined the role of career counselors in infusing systems thinking into occupational advising. The authors conducted a qualitative review and analysis of selected literature on systems thinking and analyzed trends for adaptation to career counseling practice. This analysis suggests that career counselors need to infuse systems…

  8. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Infusion pump. 880.5725 Section 880.5725 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use Therapeutic Devices § 880.5725 Infusion pump. (a) Identification....

  9. Mesenteric artery ischemia

    MedlinePlus

    ... Dead bowel - mesenteric; Dead gut - mesenteric; Atherosclerosis - mesenteric artery; Hardening of the arteries - mesenteric artery ... The arteries that supply blood to the intestines run directly from the aorta, the main artery from the heart. ...

  10. Peripheral Artery Disease

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Peripheral Artery Disease (PAD) Peripheral artery disease (PAD) refers to ... is peripheral artery disease treated? What is peripheral artery disease (PAD)? Peripheral artery disease, or PAD, refers ...

  11. Implementing and maintaining an infusion alliance.

    PubMed

    Meyer, Britt M

    2010-01-01

    Infusion therapy models are ever changing and growing in modern health care. New technologies and problems arise daily as researchers and clinicians explore our world. As technologies advance, health care costs are also skyrocketing. The vast majority of hospitalized patients will receive some form of infusion therapy during their stay, and many will continue to receive therapy after they are discharged from the inpatient setting. Infusion alliances can aid cost containment by decreasing infusion-related complication rates, affect customer satisfaction, and promote interdisciplinary collaboration. This article discusses the potential benefits of an infusion alliance, details steps for using the performance improvement process when implementing and maintaining an alliance, and outlines the components of a successful business plan. PMID:20841983

  12. Fluid delivery from infusion-pump syringes.

    PubMed

    Carl, J L; Erstad, B L; Murphy, J E; Slack, M K

    1995-07-01

    Fluid-delivery rates of five small-volume infusion-pump syringes were compared. The study consisted of a comparison of the infusion-pump syringes in their respective infusion pumps (1) set for continuous delivery at 1 mL/hr, (2) set for continuous delivery at 3 mL/hr, and (3) set to deliver 1-mL bolus volumes during continuous delivery at 4 mL/hr. The Life-care prefilled 30-mL syringe (Abbott), the DBL 30-mL syringe no. 770205 (DBL Inc.), and the Pump-Jet 30-mL syringe no. 1931 (International Medication Systems) were tested in the Lifecare PCA Plus II infusion pump no. 4100 (Abbott). The 30-mL Pump-Jet syringe no. 1911 (International Medication Systems) and the DBL 30-mL syringe no. 709700 (DBL Inc.) were tested in the Stratofuse PCA infusion pump (Baxter). The infusion pumps were set to deliver fluid continuously at 1 mL/hr for 30 hours, and the solutions were collected separately and weighed. The procedure was repeated with the infusion rate set at 3 mL/hr for 10 hours. For the third part of the study, each syringe was tested to deliver 1-mL boluses with 0, 5, 15, and 25 mL removed from the syringe. The solutions were collected and weighed before and after each bolus was delivered. The volume of solution collected was calculated by using the specific gravity of the solution. The syringes delivered significantly different volumes during the first hour of infusion at both the 1- and 3-mL/hr rates. Differences also existed across time for most of the syringes. Bolus volumes varied greatly after infusion of 0 or 5 mL of fluid but were acceptable for the remainder of the infusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7671041

  13. Soluble Urokinase Receptor Levels Are Correlated with Focal Segmental Glomerulosclerosis Lesions in IgA Nephropathy: A Cohort Study from China

    PubMed Central

    Guo, Shui-Ming; Han, Min; Chen, Mei-Xue; Ning, Yong; Pei, Guang-Chang; Li, Yue-Qiang; Dai, Wei; Ge, Shu-Wang; Deng, Yuan-Jun; Guo, Yan-Yan; Li, Xiao-Qing; Haller, Hermann; Xu, Gang; Rong, Song

    2015-01-01

    Background Soluble urokinase receptor (suPAR) may be involved in the pathological mechanisms of focal segmental glomerulosclerosis (FSGS) changes. However, it remains unclear whether suPAR is correlated with the FSGS-like lesions in IgA nephropathy (IgAN). Methods We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed. Results We found that the plasma suPAR levels were significantly correlated with age and renal function by both univariate and multivariate analysis in our IgAN patient cohort. Female had higher plasma suPAR levels and no significant correlation was observed between plasma suPAR levels and 24-h urine protein and highly sensitive C-reaction protein with multivariate analysis. In our cohort, sixty of these IgAN patients could be diagnosed with a type of FSGS lesions. The plasma suPAR levels were higher in the IgAN patients with FSGS lesions than in the IgAN patients without FSGS lesions by univariate (P < 0.0001) and multivariate (P < 0.001) analysis adjusting for other predictor variables, which might be helpful to differentiate the pathological changes with and without FSGS lesions. And the optimal cutoff value was 1806 pg/ml in this study. The plasma suPAR concentrations were also associated with the degree of tubular atrophy/interstitial fibrosis in both univariate and multivariate analysis. In multivariate analysis, the plasma suPAR levels were correlated with the percentage of crescents, not global sclerosis and arterial lesions. Conclusions Our study suggested that the plasma suPAR levels were associated with age, gender, renal function, the degree of tubular atrophy/interstitial fibrosis and the percentage of crescent formation. The plasma suPAR might be a potential predictor for the presence of FSGS pathological lesions in Chinese patients with IgAN. PMID:26380984

  14. Nebivolol increases arterial distensibility in vivo.

    PubMed

    McEniery, Carmel M; Schmitt, Matthias; Qasem, Ahmad; Webb, David J; Avolio, Alberto P; Wilkinson, Ian B; Cockcroft, John R

    2004-09-01

    Arterial stiffness is a key determinant of cardiovascular risk in hypertensive patients. beta-Blockers appear to be less effective than other drugs in improving outcome in hypertensive patients, and a potential explanation may be that beta-blockers are less effective in reducing arterial stiffness. The aim of this study was to assess the direct effect of beta-blockade on pulse wave velocity (PWV), a robust measure of arterial distensibility, using a local, ovine, hind-limb model. In addition, we hypothesized that the vasodilating beta-blocker nebivolol, but not atenolol, would increase arterial distensibility in vivo. All studies were conducted in anesthetized sheep. PWV was recorded in vivo using a dual pressure-sensing catheter placed in the common iliac artery. Intraarterial infusion of nebivolol reduced PWV by 6+/-3% at the higher dose (P<0.001), but did not alter mean arterial pressure (change of -1+/-3 mm Hg, P=0.1). In contrast, atenolol had no effect on PWV (P=0.11) despite a small drop in mean pressure (change of -5+/-3 mm Hg, P<0.01). Infusion of glyceryl trinitrate led to a dose-dependent fall in PWV, and 2 nmol/min produced a similar reduction in PWV to the higher dose of nebivolol (500 nmol/min). The effect of nebivolol on PWV was significantly attenuated during coinfusion of N(G)-monomethyl-L-arginine (P=0.003) and also during coinfusion of butoxamine (P=0.02). These results demonstrate that nebivolol, but not atenolol, increases arterial distensibility. This effect of nebivolol is mediated through the release of NO via a beta2 adrenoceptor-dependent mechanism. Thus, nebivolol may be of benefit in conditions of increased large artery stiffness, such as isolated systolic hypertension. PMID:15262912

  15. Successful lung transplantation after donor lung reconditioning with urokinase in ex vivo lung perfusion system.

    PubMed

    Inci, Ilhan; Yamada, Yoshito; Hillinger, Sven; Jungraithmayr, Wolfgang; Trinkwitz, Michael; Weder, Walter

    2014-11-01

    Acute pulmonary embolism is considered a contraindication to lung donation for transplantation as it might result in graft dysfunction. Ex vivo lung perfusion (EVLP) is a novel method to assess and recondition a questionable donor graft before transplantation. In this report we present a case of successful bilateral lung transplant after donor lung assessment and treatment with a fibrinolytic agent, urokinase, during EVLP. PMID:25441801

  16. In vitro inhibition of human malignant brain tumour cell line proliferation by anti-urokinase-type plasminogen activator monoclonal antibodies.

    PubMed Central

    Abaza, M. S.; Shaban, F. A.; Narayan, R. K.; Atassi, M. Z.

    1998-01-01

    A brain tumour-associated marker, urokinase (UK), was investigated using rabbit anti-UK polyclonal and murine anti-UK monoclonal antibodies, which were prepared by immunization with low molecular weight UK (LMW-UK) and high molecular weight urokinase (HMW-UK) synthetic peptide respectively. The polyclonal antibody cross-reacted with both LMW-UK and HMW-UK, whereas the murine MAbs were specific for HMW-UK. These immunological probes were used to study urokinase in glioma extracts, tissues, sera and cell lines that had been prepared from primary cultures of freshly dissected gliomas. Radioimmunoassays showed that glioma extracts had much higher level (5- to 44-fold) of UK than normal human brain extracts. This result was confirmed by immunoblotting of electrophoresis gels of glioma and human brain extracts. Immunohistochemical study using anti-UK MAb demonstrated much higher levels of UK in glioma tissue than normal brain tissue. Immunohistochemical study using anti-UK MAbs localized UK on the cell surface of glioma cells. Anti-UK MAbs inhibited the proliferation of AA cell lines and GB cell lines (50% to > 90%) and exerted minor effects (< or = 20%) on normal human liver, intestine and lymphocyte cell lines. Taken together, these results suggest that anti-UK MAbs may have therapeutic potential for human gliomas and cancer metastasis. Images Figure 2 Figure 3 PMID:9862567

  17. Early albumin infusion to infants at risk for respiratory distress

    PubMed Central

    Bland, R. D.; Clarke, T. L.; Harden, L. B.; Mayer, Judith L.; Ries, J. P.; Madden, W. A.; Crast, F. W.; Coyer, W. F.; Bass, J. W.

    1973-01-01

    In a randomized prospective study, 100 high-risk infants (selected on the basis of a cord serum protein level of 4·6 g/100 ml or less, gestational age under 37 weeks, birthweight 2500 g or less, and/or arterial pH below 7·25) received 8 ml/kg of either 25% salt-poor albumin or 5% dextrose in water before the age of 2 hours. All infants were then managed supportively with warmth, appropriate oxygen supplementation, isotonic fluid infusion, and close monitoring, without further administration of colloid or hypertonic alkali solutions over the first 4 hours of life. No statistically significant difference was shown between early colloid and early dextrose-water administration for either the incidence of idiopathic respiratory distress syndrome (RDS) or the mortality of high-risk infants, suggesting no apparent advantage of albumin over simple glucose-water infusion to hypoproteinaemic newborns shortly after birth. However, among the infants of 28 weeks' gestation or less admitted to the study, 3 of 4 albumin-treated patients survived, while 5 comparable infants in the dextrose-water group died within 12 hours of birth. For the 100 infants taken together there was a significant improvement in morbidity and mortality from previous experience in the same nursery, indicating that prompt supportive care, including early fluid administration, may be instrumental in reducing the incidence and severity of RDS. PMID:4749684

  18. Infant death due to air embolism from peripheral venous infusion.

    PubMed

    Sowell, Matthew W; Lovelady, Cari L; Brogdon, B G; Wecht, Cyril H

    2007-01-01

    An otherwise healthy male infant was brought to the hospital because the mother suspected superficial infection at the operative site 5 days after an inguinal hernia repair. He was admitted to the pediatric unit overnight to be evaluated by his surgeon the next morning. When a venous infusion of maintenance fluids was started, the patient immediately went into cardio-respiratory arrest and was pronounced dead after resuscitation efforts failed. Subsequently, air collections were found in both venous and arterial circulations, including the splenoportal system. Detailed review of the clinical presentation and course, laboratory results, radiological, and pathological findings, along with a review of pertinent literature provides an explanation for the death by air embolism. Apparent inconsistent findings both radiographically and at autopsy are resolved. The mechanism of distribution of air to both systemic and splenoportal circulation is discussed. We believe this to be only the eighth case reported in English-language literature of infantile death from peripheral venous infusion. In all age groups, we find only six other cases in the English-language literature of gas found concomitantly in both the systemic and portal venous systems. PMID:17209934

  19. Coronary Arteries

    MedlinePlus

    ... side of the heart is smaller because it pumps blood only to the lungs. The left coronary artery, ... heart is larger and more muscular because it pumps blood to the rest of the body. Updated August ...

  20. Overflow cascades in liquid-infused substrates

    NASA Astrophysics Data System (ADS)

    Jacobi, I.; Wexler, J. S.; Stone, H. A.

    2015-08-01

    Liquid-infused patterned surfaces offer a promising new platform for generating omniphobic surface coatings. However, the liquid infused in these surfaces is susceptible to shear-driven dewetting. Recent work [Wexler et al., "Shear-driven failure of liquid-infused surfaces," Phys. Rev. Lett. 114, 168301 (2015)] has shown how the substrate pattern in these surfaces can be designed to exploit capillary forces in order to retain infused lubricants against the action of an immiscible shear flow. In this study, we explore the behavior of the infused lubricant when external shear causes the lubricant to overflow finite or "dead-end" surface features, resulting in either temporary or permanent lubricant loss. Microfluidic experiments illustrate how both geometry and chemical Marangoni stresses within liquid-infused surfaces generate an overflow cascade in which the lubricant escapes from the substrate and forms droplets on the surface, after which the droplets depin and are washed away by the external shear flow, allowing the overflow to repeat. General guidelines are developed to estimate the onset of the different stages of the cascade with the aim of providing additional robustness criteria for the design of future liquid-infused surfaces.

  1. Infliximab-Related Infusion Reactions: Systematic Review

    PubMed Central

    Ron, Yulia; Kivity, Shmuel; Ben-Horin, Shomron; Israeli, Eran; Fraser, Gerald M.; Dotan, Iris; Chowers, Yehuda; Confino-Cohen, Ronit; Weiss, Batia

    2015-01-01

    Objective: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. Methods: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. Results: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. Conclusions: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms. PMID:26092578

  2. Infusion pump development and implications for nurses.

    PubMed

    Lee, Paul

    Infusion pumps are commonplace in today's healthcare settings and their design and development has kept pace with technology over the decades. In the 1970s and 1980s infusion pumps began to emerge in the UK market and were basic, mechanical devices with limited functions. Today, infusion pumps have a plethora of functions and features and a range of alarms to help alert the user and the patient that infusions are nearing completion, have ended or their range of sensors has detected that the infusion pump, or patient, requires attention. The role of the nurse in safely managing this ever-changing technology should not be underestimated. This paper reviews the progress made over the past 40 years in the UK healthcare setting and how the nurses have had to keep up to speed with the technology as it develops. It highlights the importance of fully integrating infusion pumps into intravenous (IV) therapy training and assessment. The important role the nurse plays is highlighted as well as exploring how he or she can help organisations better understand infusion pumps in the day-to-day management of patients undergoing intravenous therapy. PMID:26496875

  3. Pharmacokinetics and toxicology of continuously infused nitroimidazoles

    SciTech Connect

    Eifel, P.J.; Brown, J.M.

    1984-08-01

    The pharmacokinetics and toxicology of misonidazole (MISO) and SR-2508 given by continuous intraperitoneal infusion were studied in female C/sub 3/H mice. The survival (time to death) of animals receiving continuous infusions of SR-2508 and MISO was compared and related to plasma concentration, rate of infusion and total amount of drug delivered. Brain and plasma concentrations were determined by HPLC. For SR-2508, plasma concentration was directly proportional to the infusion rate. However, as the infusion rate of MISO was doubled, the plasma concentration of MISO increased approximately 6-fold, reflecting a substantial increase in the apparent half-life. The brain/plasma concentration ratio in animals infused for up to 6 days with SR-2508 remained constant, at approximately 0.09. At plasma concentrations of 0.08-1.5 mM, animals receiving SR-2508 survived approximately 3 times as long as animals exposed to a comparable plasma concentration of MISO. Even at the lowest infusion rates employed in this study, the survival of mice receiving SR-2508 was much shorter than would have been predicted if the toxicity of these two drugs were solely related to the integral brain exposure. The low brain/plasma concentration ratio of SR-2508 was maintained throughout long continuous exposures.

  4. Arterial Stiffness

    PubMed Central

    Avolio, Alberto

    2013-01-01

    Stiffness of large arteries has been long recognized as a significant determinant of pulse pressure. However, it is only in recent decades, with the accumulation of longitudinal data from large and varied epidemiological studies of morbidity and mortality associated with cardiovascular disease, that it has emerged as an independent predictor of cardiovascular risk. This has generated substantial interest in investigations related to intrinsic causative and associated factors responsible for the alteration of mechanical properties of the arterial wall, with the aim to uncover specific pathways that could be interrogated to prevent or reverse arterial stiffening. Much has been written on the haemodynamic relevance of arterial stiffness in terms of the quantification of pulsatile relationships of blood pressure and flow in conduit arteries. Indeed, much of this early work regarded blood vessels as passive elastic conduits, with the endothelial layer considered as an inactive lining of the lumen and as an interface to flowing blood. However, recent advances in molecular biology and increased technological sophistication for the detection of low concentrations of biochemical compounds have elucidated the highly important regulatory role of the endothelial cell affecting vascular function. These techniques have enabled research into the interaction of the underlying passive mechanical properties of the arterial wall with the active cellular and molecular processes that regulate the local environment of the load-bearing components. This review addresses these emerging concepts. PMID:26587425

  5. Safety of rapid intravenous of infusion acetaminophen

    PubMed Central

    2013-01-01

    Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I–III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications. PMID:23814378

  6. Safety of rapid intravenous of infusion acetaminophen.

    PubMed

    Needleman, Steven M

    2013-07-01

    Intravenous acetaminophen, Ofirmev®, is approved for management of mild to moderate pain, management of moderate to severe pain with adjunctive opioids, and reduction of fever. The product is supplied as a 100 mL glass vial. As stated in the prescribing information, it is recommended to be infused over 15 minutes. This recommendation is related to the formulation propacetamol, the prodrug to acetaminophen, approved in Europe, which caused pain on infusion, and data from the clinical development of acetaminophen. The objective of this retrospective chart review study was to show the lack of side effects of rapidly infusing intravenous acetaminophen. Charts of American Society of Anesthesiology (ASA) Class I-III ambulatory surgical patients who received only acetaminophen in the preoperative setting were reviewed for any infusion-related side effects. Using standard binomial proportion analyses and employing SAS/JMP software, all vital signs were analyzed for statistically significant changes between pre- and postinfusion values. One hundred charts were reviewed. Only one patient had pain on infusion, which lasted 10 seconds. No reported side effects or erythema was seen at the injection site. No infusions had to be slowed or discontinued. The median infusion time was 3:41 minutes. Of the vital signs monitored, only the systolic (P < 0.0001) and diastolic (P < 0.0099) blood pressures had statistically significant changes from pre- to postinfusion; however, they were of no clinical relevance. Acetaminophen can be administered as a rapid infusion with no significant infusion-related side effects or complications. PMID:23814378

  7. [Arterial thrombolysis in the lower extremity in vascular surgical practice].

    PubMed

    Entz, László; Laczkó, Agnes; Bíró, Gábor; Széphelyi, Katalin; Simonffy, Arpád; Járányi, Zsuzsanna

    2007-01-01

    The acute arterial thrombosis of the lower limb is dangerous not only for the limb, but it can cause life-threatening situation as well. That is why it is important to use different therapeutical modalities as the catheter guided intraarterial thrombolysis, which can reduce the surgical risks. All the drugs used for lysis now days are plasminogen activators. Due to the results of different studies the most appropriate drugs for optimal thrombolysis are the urokinase, the tissue-plasminogen activators and their recombinant forms. There are two major studies dealing with the effect of the different fibrinolytic drugs in comparison of the results of randomly operated patients. Both of these studies (STILE, TOPAS) determined a nearly same efficacy of both methods, operative or thrombolytic (approximately 70% amputation-free survival). Significant difference was observed in relation of occlusion of a native artery or a graft: better results could be obtained with surgery in case of arterial occlusion and conversely, it was in favor for thrombolysis if a graft was occluded. It must be noted that the thrombolysis has to be followed with endovascular or open surgical procedures in most of the cases. On the basis of our experiences and the data of literature we suggest after individual decision thrombolysis in case of graft occlusion, and surgery in case of arterial occlusion as first choice. PMID:17474303

  8. Financial analysis for the infusion alliance.

    PubMed

    Perucca, Roxanne

    2010-01-01

    Providing high-quality, cost-efficient care is a major strategic initiative of every health care organization. Today's health care environment is transparent; very competitive; and focused upon providing exceptional service, safety, and quality. Establishing an infusion alliance facilitates the achievement of organizational strategic initiatives, that is, increases patient throughput, decreases length of stay, prevents the occurrence of infusion-related complications, enhances customer satisfaction, and provides greater cost-efficiency. This article will discuss how to develop a financial analysis that promotes value and enhances the financial outcomes of an infusion alliance. PMID:20841984

  9. Pancreatic enzyme secretion during intravenous fat infusion.

    PubMed

    Burns, G P; Stein, T A

    1987-01-01

    The nutritional support of patients with pancreatic and high gastrointestinal fistulas and severe pancreatitis frequently involves intravenous fat infusion. There are conflicting reports on the effect of intravenous fat on pancreatic exocrine secretion. In 10 dogs with chronic pancreatic fistulas, pancreatic juice was collected during secretin (n = 10) or secretin + cholecystokinin (n = 4) stimulation, with and without intravenous fat infusion (5 g/hr). The hormonal-stimulated secretion of lipase, amylase, trypsin, total protein, bicarbonate, and water was unchanged during fat infusion. This study supports the use of intravenous fat as a nutritional source when it is desirable to avoid stimulation of the pancreas. PMID:2434670

  10. Single Amino Acid Substitutions in the Chemotactic Sequence of Urokinase Receptor Modulate Cell Migration and Invasion

    PubMed Central

    Franco, Paola; Pavone, Vincenzo; Mugione, Pietro; Di Carluccio, Gioconda; Masucci, Maria Teresa; Arra, Claudio; Pirozzi, Giuseppe; Stoppelli, Maria Patrizia; Carriero, Maria Vincenza

    2012-01-01

    The receptor for urokinase-type plasminogen activator (uPAR) plays an important role in controlling cell migration. uPAR binds urokinase and vitronectin extracellular ligands, and signals in complex with transmembrane receptors such as Formyl-peptide Receptors (FPR)s and integrins. Previous work from this laboratory has shown that synthetic peptides, corresponding to the uPAR88–92 chemotactic sequence, when carrying the S90P or S90E substitutions, up- or down-regulate cell migration, respectively. To gain mechanistic insights into these opposite cell responses, the functional consequences of S90P and S90E mutations in full-length uPAR were evaluated. First, (HEK)-293 embryonic kidney cells expressing uPARS90P exhibit enhanced FPR activation, increased random and directional cell migration, long-lasting Akt phosphorylation, and increased adhesion to vitronectin, as well as uPAR/vitronectin receptor association. In contrast, the S90E substitution prevents agonist-triggered FPR activation and internalization, decreases binding and adhesion to vitronectin, and inhibits uPAR/vitronectin receptor association. Also, 293/uPARS90P cells appear quite elongated and their cytoskeleton well organized, whereas 293/uPARS90E cells assume a large flattened morphology, with random orientation of actin filaments. Interestingly, when HT1080 cells co-express wild type uPAR with uPAR S90E, the latter behaves as a dominant-negative, impairing uPAR-mediated signaling and reducing cell wound repair as well as lung metastasis in nude mice. In contrast, signaling, wound repair and in vivo lung metastasis of HT1080 cells bearing wild type uPAR are enhanced when they co-express uPARS90P. In conclusion, our findings indicate that Ser90 is a critical residue for uPAR signaling and that the S90P and S90E exert opposite effects on uPAR activities. These findings may be accommodated in a molecular model, in which uPARS90E and uPARS90P are forced into inactive and active forms, respectively

  11. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    NASA Astrophysics Data System (ADS)

    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

    2013-08-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

  12. Space Tethers Programmatic Infusion Opportunities

    NASA Technical Reports Server (NTRS)

    Bonometti, J. A.; Frame, K. L.

    2005-01-01

    Programmatic opportunities abound for space Cables, Stringers and Tethers, justified by the tremendous performance advantages that these technologies offer and the rather wide gaps that must be filled by the NASA Exploration program, if the "sustainability goal" is to be met. A definition and characterization of the three categories are presented along with examples. A logical review of exploration requirements shows how each class can be infused throughout the program, from small experimental efforts to large system deployments. The economics of tethers in transportation is considered along with the impact of stringers for structural members. There is an array of synergistic methodologies that interlace their fabrication, implementation and operations. Cables, stringers and tethers can enhance a wide range of other space systems and technologies, including power storage, formation flying, instrumentation, docking mechanisms and long-life space components. The existing tether (i.e., MXER) program's accomplishments are considered consistent with NASA's new vision and can readily conform to requirements-driven technology development.

  13. Posttranscriptional regulation of urokinase receptor mRNA: identification of a novel urokinase receptor mRNA binding protein in human mesothelioma cells.

    PubMed Central

    Shetty, S; Kumar, A; Idell, S

    1997-01-01

    Treatment of human pleural mesothelioma (MS-1) cells with phorbol myristate acetate (PMA) and cycloheximide results in 17- and 10-fold, respectively, increases in steady-state expression of urokinase-type plasminogen activator receptor (uPAR) mRNA. Studies of transcriptional inhibition by actinomycin D showed four- and sixfold extensions of uPAR mRNA half-life in MS-1 cells treated with PMA and cycloheximide, respectively, suggesting that uPAR gene expression involves a posttranscriptional regulatory mechanism. Using gel mobility shift and UV cross-linking assays, we identified a 50-kDa uPAR mRNA binding protein (uPAR mRNABp) that selectively bound to a 51-nucleotide (nt) fragment of mRNA corresponding to the uPAR coding region. We investigated the possibility that this 51-nt protein binding fragment of uPAR mRNA contains regulatory information for message stability. Chimeric beta-globin/uPAR/beta-globin mRNA containing the 51-nt protein binding fragment was able to destabilize otherwise stable beta-globin mRNA. Conversely, a control chimeric beta-globin/uPAR/beta-globin mRNA containing a 51-nt fragment of the uPAR coding region that does not bind uPAR mRNABp was stable under identical conditions. Binding of uPAR mRNABp to uPAR mRNA was abolished after treatment with cycloheximide and rapidly down-regulated by PMA. These data suggest that the 51-nt protein binding fragment of uPAR mRNA may be involved in mRNA turnover as well as in cycloheximide-induced uPAR message stabilization. Our results indicate a novel mechanism of uPAR gene regulation in which cis elements within a 51-nt coding region interact with a uPAR mRNABp to regulate uPAR message stability. PMID:9032234

  14. Carotid artery surgery

    MedlinePlus

    Carotid endarterectomy; CAS surgery; Carotid artery stenosis - surgery; Endarterectomy - carotid artery ... through the catheter around the blocked area during surgery. Your carotid artery is opened. The surgeon removes ...

  15. Particulate contaminants of intravenous medications and infusions.

    PubMed

    Backhouse, C M; Ball, P R; Booth, S; Kelshaw, M A; Potter, S R; McCollum, C N

    1987-04-01

    Particulate contamination in small volume parenteral medications has been studied and compared with that found in a selection of large volume infusions. Particle counts in 39 commonly used small volume medications and 7 large volume infusions were performed by an automated light blockage method (HIAC) or by optical microscopy. Based on these results and a random survey of drug therapy of intensive care patients, it is concluded that the contribution of intravenous medications to the total particle load received by such patients is likely to be many times greater than from infusion fluids. Until firm evidence regarding the harmful systemic effects of drug particles is available and the manufacturing regulations adjusted appropriately, final in-line filtration of infusions immediately proximal to the intravenous cannula should be considered when drugs are being given intravenously. PMID:2884285

  16. Percutaneous treatment of intrabdominal abscess: urokinase versus saline serum in 100 cases using two surgical scoring systems in a randomized trial.

    PubMed

    Laborda, A; De Gregorio, M A; Miguelena, J M; Medrano, J; Gómez-Arrue, J; Serrano, C; de Blas, I; Gimenez, M; D'Agostino, H

    2009-07-01

    The purpose of this study was to assess whether regular instillation of urokinase during abscess drainage leads to an improved outcome compared to saline irrigation alone. One hundred patients referred for image-guided abdominal abscess drainage were randomized between thrice daily urokinase instillation or saline irrigation alone. At the end of the study, patient medical records were reviewed to determine drainage, study group, Altona (PIA II) and Mannheim (MPI) scoring, duration of drainage, procedure-related complications, hospital stay duration, and clinical outcome. The technical success rate of the percutaneous abscess drainage was 100%. The success or failure of abscess remission did not differ significantly between groups (success rate of 91.5% in the urokinase group vs. 88.8% in the saline group; failure rate was of 8.5 vs. 21.2%, respectively); however, days of drainage, main hospital stay, and overall costs were significantly reduced in patients treated with urokinase compared to the control group (P < 0.05). No adverse effects from urokinase were observed. Surgical scores were a useful homogeneity factor, and MPI showed a good correlation with prognosis, while PIA results did not have a significant correlation. For drainage of complex abscesses (loculations, hemorrhage, viscous material), fibrinolytics safely accelerate drainage and recovery, reducing the length of the hospital stay and, therefore, the total cost. PMID:19190912

  17. Acute Ischemic Stroke Involving Both Anterior and Posterior Circulation Treated by Endovascular Revascularization for Acute Basilar Artery Occlusion via Persistent Primitive Trigeminal Artery

    PubMed Central

    Fujita, Atsushi; Hosoda, Kohkichi; Kohmura, Eiji

    2016-01-01

    We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke. PMID:27446523

  18. Acute Ischemic Stroke Involving Both Anterior and Posterior Circulation Treated by Endovascular Revascularization for Acute Basilar Artery Occlusion via Persistent Primitive Trigeminal Artery.

    PubMed

    Imahori, Taichiro; Fujita, Atsushi; Hosoda, Kohkichi; Kohmura, Eiji

    2016-07-01

    We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke. PMID:27446523

  19. Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

    PubMed Central

    Saleem, Moin A.; Meijers, Björn

    2016-01-01

    Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels. PMID:27504461

  20. Density enhanced phosphatase-1 down-regulates urokinase receptor surface expression in confluent endothelial cells

    PubMed Central

    Brunner, Patrick M.; Heier, Patricia C.; Mihaly-Bison, Judit; Priglinger, Ute; Binder, Bernd R.

    2011-01-01

    VEGF165, the major angiogenic growth factor, is known to activate various steps in proangiogenic endothelial cell behavior, such as endothelial cell migration and invasion, or endothelial cell survival. Thereby, the urokinase-type plasminogen activator (uPA) system has been shown to play an essential role not only by its proteolytic capacities, but also by induction of intracellular signal transduction. Therefore, expression of its cell surface receptor uPAR is thought to be an essential regulatory mechanism in angiogenesis. We found that uPAR expression on the surface of confluent endothelial cells was down-regulated compared with subconfluent proliferating endothelial cells. Regulation of uPAR expression was most probably affected by extracellular signal-regulated kinase 1/2 (ERK1/2) activation, a downstream signaling event of the VEGF/VEGF-receptor system. Consistently, the receptor-like protein tyrosine phosphatase DEP-1 (density enhanced phosphatase-1/CD148), which is abundantly expressed in confluent endothelial cells, inhibited the VEGF-dependent activation of ERK1/2, leading to down-regulation of uPAR expression. Overexpression of active ERK1 rescued the DEP-1 effect on uPAR. That DEP-1 plays a biologic role in angiogenic endothelial cell behavior was demonstrated in endothelial cell migration, proliferation, and capillary-like tube formation assays in vitro. PMID:21304107

  1. [Preparation of novel magnetic dextran affinity adsorbents and their application to purify urokinase].

    PubMed

    Dong, Y S; Liang, F; Yu, X Y; Guo, L A; Chang, J H

    2001-01-01

    The reverse phase suspension and embedment technique were adopted to prepare magnetic dextran microsphere (MDMS). The dispersion medium was mixture of some organic solvents. Span-80 was used as stabilizer. The aqueous dextran with magnetic fluid was suspended in dispersion medium with epichlorohydrin as cross-linking reagent. The mixture was stirred for 30 minutes at room temperature and then heated at 70 degrees C for 4 hours, MDMS was thus obtained. MDMS was activated by epichlorohydrin on which 6-aminohexanoic acid, glycine or ethylene diamine was bonded as spacers. Then it was coupled with p-aminobenzamide, L-arginine methyl ester or guanidohexanoic acid and five magnetic affinity adsorbents were prepared. The MDMS was polydisperse particles with the size of 50-300 meshes and the content of Fe3O4 was about 6.2 per cent in the MDMS. Influence of some parameters such as viscosity and density of organic phase, the volume ratio of organic and aqueous phase, the quantity of surfactant and stirring speed on preparing MDMS was studied. Magnetic affinity adsorbents were used to purify crude urokinase in a bath mode and the effect of coupling reagents and ligands on results of purification was discussed. The bioactivity recovery was 40.0 to 60.7 per cent, the purification-fold was between 14.9 and 32.8, and the adsorptive capacity varies from 89 mg to 121 mg per milliliter of adsorbent. PMID:12541840

  2. Challenges for drug discovery - a case study of urokinase receptor inhibition

    PubMed Central

    Chen, Zhuo; Lin, Lin; Huai, Qing; Huang, Mingdong

    2009-01-01

    Urokinase receptor (uPAR) is a widely recognized target for potential treatment of cancer. The development of uPAR inhibitors has been going on for over a decade. Despite the identification and validation of many highly potent hits using screening or medicinal approaches, none of them has been moved further along the drug discovery pipeline. The development of uPAR inhibitors exemplifies several challenges now faced by drug discovery. These include 1) hydrophobicity and thus poor bioavailability of the inhibitors from screening approaches; 2) specificity of the inhibitor, where a peptidyl inhibitor causes conformational change of the receptor; 3) species specificity, where some inhibitors developed based on the human receptor do not inhibit the murine receptor and thus cannot be validated in mouse models. The recently determined crystal structures of uPAR in complex with its ligand or inhibitor not only provide the structural insight to understand these challenges but also offer a potential solution for further inhibitor development and thus illustrate the importance of structural information in facilitating drug discovery. PMID:20025562

  3. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

    SciTech Connect

    Patecki, Margret; Schaewen, Markus von; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika . E-mail: angelika.kusch@charite.de

    2007-08-03

    The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury.

  4. Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.

    PubMed

    De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai

    2016-07-01

    Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. PMID:27189837

  5. Terminalia catappa attenuates urokinase-type plasminogen activator expression through Erk pathways in Hepatocellular carcinoma

    PubMed Central

    2014-01-01

    Background The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. In our previous studies, we have reported that Terminalia catappa leaf extract (TCE) exerts antimetastasis effects on HCC cells. However, the molecular mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have not been thoroughly investigated, and remain poorly understood. Methods The activities and protein levels of u-PA were determined by casein zymography and western blotting. Transcriptional levels of u-PA were detected by real-time PCR and promoter assays. Results We found that treatment of Huh7 cells with TCE significantly reduced the activities, protein levels and mRNA levels of u-PA. A chromatin immunoprecipitation (ChIP) assay showed that TCE inhibited the transcription protein of nuclear factors SP-1 and NF-κB. TCE also did inhibit the effects of u-PA by reducing the phosphorylation of ERK1/2 pathway. Conclusions These results show that u-PA expression may be a potent therapeutic target in the TCE-mediated suppression of HCC metastasis. PMID:24886639

  6. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

    PubMed Central

    Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

    2014-01-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

  7. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.

    PubMed

    Spinale, Joann M; Mariani, Laura H; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X; Wong, Hetty N; Troost, Jonathan P; Gadegbeku, Crystal A; Gipson, Debbie S; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B

    2015-03-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS. PMID:25354239

  8. Regulation of plasminogen activator inhibitor-1 and urokinase by hyaluronan fragments in mouse macrophages.

    PubMed

    Horton, M R; Olman, M A; Bao, C; White, K E; Choi, A M; Chin, B Y; Noble, P W; Lowenstein, C J

    2000-10-01

    Pulmonary inflammation and fibrosis are characterized by increased turnover and production of the extracellular matrix as well as an impairment of lung fibrinolytic activity. Although fragments of the extracellular matrix component hyaluronan induce macrophage production of inflammatory mediators, the effect of hyaluronan on the fibrinolytic mediators plasminogen activator inhibitor (PAI)-1 and urokinase-type plasminogen activator (uPA) is unknown. This study demonstrates that hyaluronan fragments augment steady-state mRNA, protein, and inhibitory activity of PAI-1 as well as diminish the baseline levels of uPA mRNA and inhibit uPA activity in an alveolar macrophage cell line. Hyaluronan fragments alter macrophage expression of PAI-1 and uPA at the level of gene transcription. Similarly, hyaluronan fragments augment PAI-1 and diminish uPA mRNA levels in freshly isolated inflammatory alveolar macrophages from bleomycin-treated rats. These data suggest that hyaluronan fragments influence alveolar macrophage expression of PAI-1 and uPA and may be a mechanism for regulating fibrinolytic activity during lung inflammation. PMID:11000131

  9. Electroanalysis of pM-levels of urokinase plasminogen activator in serum by phosphorothioated RNA aptamer.

    PubMed

    Jarczewska, Marta; Kékedy-Nagy, László; Nielsen, Jesper S; Campos, Rui; Kjems, Jørgen; Malinowska, Elżbieta; Ferapontova, Elena E

    2015-06-01

    Protein biomarkers of cancer allow a dramatic improvement in cancer diagnostics as compared to the traditional histological characterisation of tumours by enabling a non-invasive analysis of cancer development and treatment. Here, an electrochemical label-free assay for urokinase plasminogen activator (uPA), a universal biomarker of several cancers, has been developed based on the recently selected uPA-specific fluorinated RNA aptamer, tethered to a gold electrode via a phosphorothioated dA tag, and soluble redox indicators. The binding properties of the uPA-aptamer couple and interference from the non-specific adsorption of bovine serum albumin (BSA) were modulated by the electrode surface charge. A nM uPA electroanalysis at positively charged surfaces, complicated by the competitive adsorption of BSA, was tuned to the pM uPA analysis at negative surface charges of the electrode, being improved in the presence of negatively charged BSA. The aptamer affinity for uPA displayed via the binding/dissociation constant relationship correspondingly increased, ca. three orders of magnitude, from 0.441 to 367. Under optimal conditions, the aptasensor allowed 10(-12)-10(-9) M uPA analysis, also in serum, being practically useful for clinical applications. The proposed strategy for optimization of the electrochemical protein sensing is of particular importance for the assessment and optimization of in vivo protein ligand binding by surface-tethered aptamers. PMID:25620243

  10. The steady states and dynamics of urokinase-mediated plasmin activation.

    PubMed

    Venkatraman, Lakshmi; Yu, Hanry; Bhowmick, Sourav S; Dewey, Forbes; Tucker-Kellogg, Lisa

    2010-01-01

    Plasmin and urokinase-type plasminogen activator (uPA) are ubiquitous proteases regulating the extracellular environment. They can activate each other via proteolytic cleavage, suggesting the potential for complex dynamic behaviors that could be elucidated by computational modeling. Ordinary differential equations are constructed to model the activation dynamics of plasminogen into plasmin, and single-chain uPA (scUPA) into two-chain uPA (tcUPA). Computational simulations and phase plane analysis reveal two stable steady states for the activation of each protein. Bifurcation analysis shows the in silico system to be bistable. Cell-free experiments verify the system to have ultrasensitive activation behavior, where scUPA is the stimulus and plasmin the output. Furthermore, two significantly different steady states could be seen in vitro for the same stimulus levels, depending on the initial activation level of the plasmin. The switch-like dynamics of the uPA-plasmin system could have potential relevance to many normal and disease processes including angiogenesis, migration and metastasis, wound healing and fibrosis. PMID:19908371

  11. Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.

    PubMed

    Bao, Ying-Na; Cao, Xue; Luo, Dong-Hua; Sun, Rui; Peng, Li-Xia; Wang, Lin; Yan, Yong-Pan; Zheng, Li-Sheng; Xie, Ping; Cao, Yun; Liang, Ying-Ying; Zheng, Fang-Jing; Huang, Bi-Jun; Xiang, Yan-Qun; Lv, Xing; Chen, Qiu-Yan; Chen, Ming-Yuan; Huang, Pei-Yu; Guo, Ling; Mai, Hai-Qiang; Guo, Xiang; Zeng, Yi-Xin; Qian, Chao-Nan

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target. PMID:24763226

  12. [Perioperative infusion therapy in children].

    PubMed

    Altemeyer, K H; Kraus, G B

    1990-03-01

    An incorrect fluid therapy can lead to serious complications considerably more rapidly in children, especially in newborns and infants, than in adults. The pediatric patient has a limited range of compensation for maintenance of fluid and electrolyte balance. Precise knowledge of the physiological age-dependent fluid balance, i.e. the large extracellular space, the developing renal function, the increased metabolism, the acid-base state, the electrolyte balance with the relatively higher sodium and chloride requirements must be the basis of an adequate fluid therapy. The basic fluid requirement (normal fluid and electrolyte requirement) varies with age and is influenced considerably by environmental conditions, body temperature and metabolism. For substitution of this basic fluid requirement one-third to one-half strength electrolyte solution in 5% dextrose is used, the amount depending on age. The perioperative fluid requirement, however, has to be calculated with due consideration for the characteristic changes in fluid and electrolyte balance during anaesthesia and surgery, the preoperative fasting period, drug effects of anesthetics, hormonal changes and ventilation; it is higher than the basic fluid requirement (infants 6-8 ml.kg-1.h-1, toddlers 4-6 ml.kg.h-1, schoolchildren 2-4 ml.kg-1.h-1). For intraoperative fluid therapy infusions with an increased sodium concentration (70-100 mmol/l) or Ringer's lactate (Na+ = 130 mmol/l) must be used. On no account must electrolyte-free solutions, e.g., 5-10% glucose, be used intraoperatively, as they can lead to water intoxication. The third-space requirements compensate for the additional losses by drainage, third-space deficits by evaporation and gastric and enteral secretions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2184693

  13. Fiberoptic observation of thrombosis and thrombolysis in isolated human coronary arteries.

    PubMed

    Uchida, Y; Masuo, M; Tomaru, T; Kato, A; Sugimoto, T

    1986-10-01

    Coronary arteries isolated from cadavers autopsied within 7 hours after death were perfused with canine arterial blood, and the processes of thrombus formation at the segments stenosed with atheroma and the thrombolytic effects of urokinase were investigated by angioscopy. Ten minutes of blood perfusion caused thin mural thrombi localized at the stenotic or nonstenotic segments. During 30 minutes of blood perfusion, the thin mural thrombi of the outlet or inlet of the segment grew into a doughnut-shaped thrombus. Also, the thin mural thrombi in the stenotic segment grew into a streamer-like thrombus and drifted downstream. These thrombi grew in size with increasing perfusion time and finally obstructed the stenotic segment. Globular thrombi close to the outlet also were formed in a few preparations. Unlike the thrombi at the stenotic segment, the mural thrombi in the nonstenotic segments did not grow into massive thrombi. The thrombi were reduced in size within 10 minutes of perfusion with 320 U/ml or more of urokinase. During thrombolysis, sandstorm-like dispersion of the blood cells occurred, small fragments detached from the mother thrombus and flew downstream, or the fibrin core of the thrombus was exposed. The results indicate the usefulness of angioscopy for the dynamic and serial investigation of thrombosis and thrombolysis. PMID:3766368

  14. Antidiuretic Effect of Eel ANP Infused at Physiological Doses in Conscious, Seawater-Adapted Eels, Anguilla japonica.

    PubMed

    Takei, Y; Kaiya, H

    1998-06-01

    Atrial natriuretic peptide (ANP) is known as a potent natriuretic/diuretic hormone in vertebrates. However, eel ANP infused at doses that did not alter arterial blood pressure (0.3-3.0 pmol/kg/min) decreased urine volume and increased urinary Na concentration in seawater (SW)-adapted eels but not in freshwater (FW)-adapted eels. The renal effects were dose-dependent and disappeared after infusate was switched back to a vehicle (0.9% NaCl). Urinary Na excretion (volume x Na concentration) did not change during ANP infusion. ANP infusion increased plasma ANP concentration, but the increase at the highest dose was still within those observed endogenously after injection of hypertonic saline. Urinary Mg and Ca concentrations increased during ANP infusion in SW eels, but urinary Ca excretion decreased in FW eels. Plasma Na concentration profoundly decreased during ANP infusion only in SW eels, suggesting that ANP stimulates Na extrusion via non-renal routes. These results indicate that ANP is a hormone which specifically extrudes Na ions and thereby promotes SW adaptation in the eel. This is in sharp contrast with mammals where ANP is a volume regulating hormone that extrudes both Na and water. PMID:18466004

  15. Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

    SciTech Connect

    Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

    1986-11-01

    Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of /sup 125/I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting.

  16. Popliteal artery trauma. Systemic anticoagulation and intraoperative thrombolysis improves limb salvage.

    PubMed Central

    Melton, S M; Croce, M A; Patton, J H; Pritchard, F E; Minard, G; Kudsk, K A; Fabian, T C

    1997-01-01

    OBJECTIVE: This study was conducted to evaluate those factors associated with popliteal artery injury that influence amputation, with emphasis placed on those that the surgeon can control. SUMMARY BACKGROUND DATA: Generally accepted factors impacting amputation after popliteal artery injury include blunt trauma, prolonged ischemic times, musculoskeletal injuries, and venous disruption. Amputation ultimately results from microvascular thrombosis and subsequent tissue necrosis, predisposed by the paucity of collaterals around the knee. METHODS: Patients with popliteal artery injuries over the 10-year period ending November 1995 were identified from the trauma registry. Preoperative (demographics, mechanism and severity of injury, vascular examination, ischemic times) and operative (methods of arterial repair, venous repair-ligation, anticoagulation-thrombolytic therapy, fasciotomy) variables were studied. Severity of extremity injury was quantitated by the Mangled Extremity Severity Score (MESS). Amputations were classified as primary (no attempt at vascular repair) or secondary (after vascular repair). After univariate analysis, logistic regression analysis was performed to identify the independent risk factors for limb loss. RESULTS: One hundred two patients were identified; 88 (86%) were males and 14 (14%) were females. Forty injuries resulted from blunt and 62 from penetrating trauma. There were 25 amputations (25%; 11 primary and 14 secondary). Patients with totally ischemic extremities (no palpable or Doppler pulse) more likely were to be amputated (31% vs. 13%; p < 0.04). All requiring primary amputations had severe soft tissue injury and three had posterior tibial nerve transection; the average MESS was 7.6. Logistic regression analysis identified independent factors associated with secondary amputation: blunt injury (p = 0.06), vein injury (p = 0.06), MESS (p = 0.0001), heparin-urokinase therapy (p = 0.05). There were no complications with either heparin or

  17. Platelet--arterial synthetic graft interaction and its modification

    SciTech Connect

    Callow, A.D.; Connolly, R.; O'Donnell, T.F. Jr.; Gembarowicz, R.; Keough, E.; Ramberg-Laskaris, K.; Valeri, C.R.

    1982-11-01

    We compared the in vivo platelet reactivity of two commonly used clinical grafts, Dacron and expanded polytetrafluoroethylene (PTFE), with that of a control autogenous artery graft and assessed whether platelet reactivity was modified by the platelet-antiaggregating agent prostacyclin (PGI2) (epoprostenol). Grafts were randomly placed into the carotid arteries of 21 baboons. Platelets labeled with /sup 111/In were infused within one hour after implantation graft for gamma camera scanning of platelet uptake. The accumulation of platelets on Dacron grafts began almost immediately after injection and reached a peak after one to two hours. The PTFE and control autogenous artery grafts accumulated comparable small amounts of platelets. Prostacyclin was then infused in a second series of baboons with Dacron grafts, at a rate of 150 to 200 ng/kg/min. It prevented the usual platelet uptake when administered concomitant with graft implantation and reduced previously established platelet activity.

  18. Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion

    PubMed Central

    Fidler, Meredith C; Barshop, Bruce A; Gangoiti, Jon A; Deutsch, Reena; Martin, Michael; Schneider, Jerry A; Dohil, Ranjan

    2007-01-01

    Aims Although cysteamine was first used in the treatment of cystinosis in 1976 and approved by the FDA as cysteamine bitartrate (Cystagon™) in 1994, surprisingly little pharmacological data are available for this compound. Cysteamine and its related drugs are currently being evaluated for the treatment of Huntington’s and Parkinson’s disease. The aim of te study was to understand the pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion. Method Cysteamine bitartrate was delivered through a naso-enteric catheter into the stomach (n = 8), small intestine (n = 8) and caecum (n = 4) of normal subjects. Plasma cysteamine concentrations were determined using LC-MS/MS. Results The rate and extent of drug absorption were assessed by comparing AUC(0, ∞), Cmax and tmax, among the gastrointestinal infusion sites. Total cysteamine exposure, expressed as area under the curve (AUC(0, ∞)) was greatest when the drug was infused into the small intestine (4331.3 ± 1907.6 min × µm) followed by stomach (3901.9 ± 1591.9 min × µm) and caecum (3141.4 ± 1627.6 min × µm). Cysteamine infusion into the small intestine resulted in the most rapid rise to maximal plasma concentrations (tmax = 21 ± 0.56 min); tmax was delayed to 50 ± 26 min and 64 ± 26 min after gastric and caecal infusion, respectively. The maximum cysteamine plasma concentration (Cmax) was reached after infusion of the drug into the small intestine (51 ± 21 µm), which was higher than plasma Cmax concentrations after gastric (39 ± 16 µm) and caecal infusion (23 ± 15 µm). Conclusions The pharmacokinetic data generated help extend our understanding of cysteamine. PMID:17229040

  19. Ultrastructure of an arterial lesion induced in rats by fenoldopam mesylate, a dopaminergic vasodilator.

    PubMed Central

    Bugelski, P. J.; Vockley, C. M.; Sowinski, J. M.; Arena, E.; Berkowitz, B. A.; Morgan, D. G.

    1989-01-01

    Fenoldopam mesylate (FM) is a dopaminergic vasodilator with demonstrated efficacy and a favourable safety profile in hypertensive and congestive heart failure patients. FM produced a novel arterial lesion in renal and splanchnic arteries of rats, but not dogs or monkeys. The studies reported here were undertaken to investigate the ultrastructure of the arterial lesion induced in rats by FM in an attempt to shed light on its pathogenesis. Rats were infused intravenously with FM, either 50 micrograms/kg/min for 1 or 4 h, or 5 or 100 micrograms/kg/min for 24 h. Control rats were infused for 4 or 24 h with vehicle alone. Perfusion-fixed tissue from the stomach and pancreas of control and drug-treated rats was examined by transmission electron microscopy. No arterial lesions were seen in rats infused with the drug for 1 or 4 h, or in control rats. All drug-treated rats infused with 5 or 100 micrograms/kg/min of FM for 24 h had lesions in subserosal gastric arteries and interlobular pancreatic arteries. In areas of mild arterial damage, medial smooth muscle cells contained intracytoplasmic pseudovacuoles, autophagic vacuoles, and electron-dense, myofilamentous inclusions. More severe lesions were characterized by overt medial necrosis and haemorrhage. The endothelium of affected arteries was invariably intact, except in areas of severe medial damage. The internal elastic lamina and connective tissue elements within the arterial wall were unaffected. These findings suggest that medial smooth muscle cells are the primary site of damage caused by fenoldopam mesylate in splanchnic arteries of the rat. This iatrogenic arterial lesion could provide an interesting model to study the response of medial smooth muscle to pharmacologically mediated injury. Images Fig. 6 Fig. 5 Fig. 2 Fig. 3 Fig. 4 Fig. 7 Fig. 8 Fig. 9 PMID:2567179

  20. Successful Thrombolysis and Spasmolysis of Acute Leg Ischemia after Accidental Intra-arterial Injection of Dissolved Flunitrazepam Tablets

    SciTech Connect

    Radeleff, B. Stampfl, U.; Sommer, C.-M.; Bellemann, N.; Hyhlik-Duerr, A.; Weber, M.-A.; Boeckler, D.; Kauczor, H.-U.

    2011-10-15

    A 37-year-old man with known intravenous drug abuse presented in the surgical ambulatory care unit with acute leg ischemia after accidental intra-arterial injection of dissolved flunitrazepam tablets into the right femoral artery. A combination of anticoagulation, vasodilatation, and local selective and superselective thrombolysis with urokinase was performed to salvage the leg. As a result of the severe ischemia-induced pain, the patient had to be monitored over the complete therapy period on the intensive care unit with permanent administration of intravenous fluid and analgetics. We describe the presenting symptoms and the interventional technique, and we discuss the recent literature regarding the management of accidental intra-arterial injection of dissolved flunitrazepam tablets.

  1. Blood pressure regulation in third-trimester pregnant women receiving tocolytic terbutaline infusion.

    PubMed

    Bremme, K; Eneroth, P; Carsjö, B M; Nilsson, B

    1986-10-01

    Terbutaline (20 micrograms/min) was infused during 30 min in 17 women in whom a manual external manipulation of a breech presentation was going to be attempted. A significant increase in systolic (P = 0.003) and a decrease in diastolic blood pressure (P = 0.04) was noted at the end of the infusion but no change in mean arterial blood pressure was obtained. At the same time aldosterone serum levels had dropped significantly (P = 0.009) and plasma angiotensin II showed a marked increase (P less than 0.001) which continued during the next 30 min. All changes were normalized after the infusion. The angiotensin-converting enzyme activity remained unchanged, as did vasopressin plasma levels. The combined results of terbutaline provocation have been interpreted to mean that blood pressure regulation in third-trimester pregnant women is similar to that in nonpregnant individuals. The increase in dehydroepiandrosterone sulphate (P less than 0.05) noted at the end of infusion was suggested to be related to the blood pressure changes and was unrelated to fluctuations in serum cortisol. The latter steroid increased between 30 and 60 min, e.g. during the manual external manipulation, and was interpreted as being due to maternal stress. PMID:3023154

  2. Antagonism of renal and systemic responses to endothelin-1 infusion with PD 145065.

    PubMed

    Wellings, R P; Corder, R; Doherty, A M; Vane, J R

    1994-04-21

    The antagonism by PD 145065 (Ac-D-Bhg-L-Leu-L-Asp-L-Ile-L-Ile-L-Trp; D-Bhg = 5H-dibenzyl[a,d]cycloheptene-10,11-dihydroglycine), a non-selective endothelin ETA and ETB receptor antagonist, of the pressor and renal haemodynamic responses to an infusion of endothelin-1 was investigated in the anaesthetised rat. Infusion of endothelin-1 at 2 or 4 pmol/min/rat for 2 h produced a significant increase in mean arterial blood pressure and renal vascular resistance. Glomerular filtration rate was reduced by both infusion rates of endothelin-1 (-34% for the lower rate and -72% for the higher rate), but only the high rate significantly reduced renal blood flow (-64%). These effects of endothelin-1 were completely blocked by infusion of PD 145065 (0.05 mg/min/rat), demonstrating the efficacy of this antagonist in preventing the actions of endothelin-1 in vivo. These results lend support to an involvement of endothelin ETB receptors in the renal effects of endothelin-1. PMID:8050471

  3. Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep.

    PubMed

    Carey, Luke C; Su, Yixin; Valego, Nancy K; Rose, James C

    2006-08-01

    The late-gestation plasma cortisol surge in the sheep fetus is critical for stimulating organ development and parturition. Increased adrenal responsiveness is one of the key reasons for the surge; however, the underlying mechanisms are not fully understood. Our recent studies suggest that ACTH-mediated increased expression of ACTH receptor (ACTH-R) and steroid acute regulatory protein (StAR) may play a role in enhancing responsiveness. Hence, we examined effects of ACTH infusion in fetal sheep on mRNA expression of these two mediators of adrenal responsiveness and assessed the functional consequences of this treatment in vitro. Fetuses of approximately 118 and 138 days of gestational age (dGA) were infused with ACTH-(1-24) for 24 h. Controls received saline infusion. Arterial blood was sampled throughout the infusion. Adrenals were isolated and analyzed for ACTH-R and StAR mRNA, or cells were cultured for 48 h. Cells were stimulated with ACTH, and medium was collected for cortisol measurement. Fetal plasma ACTH and cortisol concentrations increased over the infusion period in both groups. ACTH-R mRNA levels were significantly higher in ACTH-infused fetuses in both the 118 and 138 dGA groups. StAR mRNA increased significantly in both the 118 and 138 dGA groups. Adrenal cells from ACTH-infused fetuses were significantly more responsive to ACTH stimulation in terms of cortisol secretion than those from saline-infused controls. These findings demonstrate that increases in circulating ACTH levels promote increased expression of ACTH-R and StAR mRNA and are coupled to heightened adrenal responsiveness. PMID:16478774

  4. Hypoxia stimulates urokinase receptor expression through a heme protein-dependent pathway.

    PubMed

    Graham, C H; Fitzpatrick, T E; McCrae, K R

    1998-05-01

    Hypoxia underlies a number of biologic processes in which cellular migration and invasion occur. Because earlier studies have shown that the receptor for urokinase-type plasminogen activator (uPAR) may facilitate such events, we studied the effect of hypoxia on the expression of uPAR by first trimester human trophoblasts (HTR-8/SVneo) and human umbilical vein endothelial cells (HUVEC). Compared with control cells cultured under standard conditions (20% O2), HTR-8/SVneo cells and HUVEC cultured in 1% O2 expressed more uPAR, as determined by flow cytometric and [125I]-prourokinase ligand binding analyses. Increased uPAR expression paralleled increases in uPAR mRNA. The involvement of a heme protein in the hypoxia-induced expression of uPAR was suggested by the observations that culture of cells with cobalt chloride, or sodium 4, 5-dihydroxybenzene-1,3-disulfonate (Tiron), an iron-chelating agent, also stimulated uPAR expression, and that the hypoxia-induced uPAR expression was inhibited by adding carbon monoxide to the hypoxic atmosphere. Culture of HTR-8/SVneo cells with vascular endothelial growth factor (VEGF) did not increase uPAR mRNA levels, suggesting that the hypoxia-mediated effect on uPAR expression by these cells did not occur through a VEGF-dependent mechanism. The functional importance of these findings is suggested by the fact that HTR-8/SVneo cells cultured under hypoxia displayed higher levels of cell surface plasminogen activator activity and greater invasion through a reconstituted basement membrane. These results suggest that hypoxia may promote cellular invasion by stimulating the expression of uPAR through a heme protein-dependent pathway. PMID:9558386

  5. Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

    PubMed Central

    Chen, Yushu; Gong, Li; Gao, Ning; Liao, Jichun; Sun, Jiayu; Wang, Yuqing; Wang, Lei; Zhu, Pengjin; Fan, Qing; Wang, Yongqiang Andrew; Zeng, Wen; Mao, Hui; Yang, Lily; Gao, Fabao

    2015-01-01

    Purpose To translate a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO) nanoparticles (uPAR-targeted human ATF-IONPs) into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys. Methods We assessed the changes in the following: magnetic resonance imaging (MRI) signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP) or without a PEG (ATF-IONP) coating. Results The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells, white blood cells, hemoglobin level, and platelets remained normal during the 3 months of the study. Conclusion All of the results suggest that a transient injury in terms of normal organ functions, but no microscopic necrotic lesions, was observed at a systemic delivery dose of 5 mg/kg of iron equivalent concentration in the acute phase, and that no chronic toxicity was found 3 months after the injection. Therefore, we conclude that uPAR-targeted IONPs have the potential to be used as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of

  6. A chimeric platelet-targeted urokinase prodrug selectively blocks new thrombus formation

    PubMed Central

    Fuentes, Rudy E.; Zaitsev, Sergei; Ahn, Hyun Sook; Hayes, Vincent; Kowalska, M. Anna; Lambert, Michele P.; Wang, Yuhuan; Siegel, Donald L.; Bougie, Daniel W.; Aster, Richard H.; Myers, Daniel D.; Stepanova, Victoria; Cines, Douglas B.; Muzykantov, Vladimir R.; Poncz, Mortimer

    2015-01-01

    The use of fibrinolytic agents to prevent new thrombus formation is limited by an increased risk of bleeding due to lysis of hemostatic clots that prevent hemorrhage in damaged blood vessels. We sought to develop an agent that provides thromboprophylaxis without carrying a significant risk of causing systemic fibrinolysis or disrupting hemostatic clots. We previously showed that platelet (PLT) α granule–delivered urokinase plasminogen activator (uPA) is highly effective in preventing thrombosis, while being associated with little systemic fibrinolysis or bleeding. Here, we generated a chimeric prodrug composed of a single-chain version of the variable region of an anti-αIIbβ3 mAb fused to a thrombin-activatable, low-molecular-weight pro-uPA (PLT/uPA-T). PLT/uPA-T recognizes human αIIbβ3 on both quiescent and activated platelets and is enzymatically activated specifically by thrombin. We found that this prodrug binds tightly to human platelets even after gel filtration, has a prolonged half-life in mice transgenic for human αIIb compared with that of uPA-T, and prevents clot formation in a microfluidic system. Importantly, in two murine injury models, PLT/uPA-T did not lyse preexisting clots, even when administration was delayed by as little as 10 minutes, while it concurrently prevented the development of nascent thrombi. Thus, PLT/uPA-T represents the prototype of a platelet-targeted thromboprophylactic agent that selectively targets nascent over preexisting thrombi. PMID:26690701

  7. Urokinase, a constitutive component of the inflamed synovial fluid, induces arthritis

    PubMed Central

    Jin, Tao; Tarkowski, Andrej; Carmeliet, Peter; Bokarewa, Maria

    2003-01-01

    Urokinase plasminogen activator (uPA) is an important regulator of fibrinolysis in synovial fluid. An increase of uPA activity and expression of its receptor have been reported in joints of patients with rheumatoid arthritis (RA). The aim of the present study was to assess the arthritogenic capacity of uPA and the mechanisms by which this effect is mediated. uPA was injected into the knee joints of healthy mice, and morphological signs of arthritis were assessed 4 days after the injection. The prerequisite of different leukocyte populations for the development of uPA-triggered arthritis was assessed by selective cell depletion. The inflammatory capacity of uPA was assessed in vitro. Finally, levels of uPA were measured in 67 paired blood and synovial fluid samples from RA patients. The synovial fluid from RA patients displayed higher levels of uPA compared with blood samples. Morphological signs of arthritis were found in 72% of uPA-injected joints compared with in only 18% of joints injected with PBS (P < 0.05). Synovitis was characterised by infiltration of CD4-Mac-1+ mononuclear cells, by the formation of pannus and by occasional cartilage destruction. The absence of monocytes and lymphocytes diminished the frequency of synovitis (P < 0.01), indicating an arthritogenic role of both these leukocyte populations. Synthetic uPA inhibitor downregulated the incidence of uPA-triggered arthritis by 50%. uPA induced arthritis, stimulating the release of proinflammatory cytokines IL-6, IL-1β and tumour necrosis factor alpha. Accumulation of uPA locally in the joint cavity is a typical finding in erosive RA. uPA exerts potent arthritogenic properties and thus may be viewed as one of the essential mediators of joint inflammation. PMID:12716448

  8. Probing Binding and Cellular Activity of Pyrrolidinone and Piperidinone Small Molecules Targeting the Urokinase Receptor

    PubMed Central

    Mani, Timmy; Liu, Degang; Zhou, Donghui; Li, Liwei; Knabe, William Eric; Wang, Fang; Oh, Kyungsoo; Meroueh, Samy O.

    2014-01-01

    The urokinase receptor (uPAR) is a cell-surface protein that is part of an intricate web of transient and tight protein interactions that promote cancer cell invasion and metastasis. Here we evaluate the binding and biological activity of a new class of pyrrolidinone (3) and piperidinone (4) compounds, along with derivatives of previously-identified pyrazole (1) and propylamine (2) compounds. Competition assays revealed that the compounds displaced a fluorescently-labeled peptide (AE147-FAM) with inhibition constant Ki ranging from 6 to 63 μM. Structure-based computational pharmacophore analysis followed by extensive explicit-solvent molecular dynamics simulations and free energy calculations suggested pyrazole-based 1a and piperidinone-based 4 adopt different binding modes, despite their similar two-dimensional structures. In cells, compounds 1b and 1f showed significant inhibition of breast MDA-MB-231 and pancreatic ductal adenocarcinoma (PDAC) cell proliferation, but 4b exhibited no cytotoxicity even at concentrations of 100 μM. 1f impaired MDA-MB-231 invasion, adhesion, and migration in a concentration-dependent manner, while 4b inhibited only invasion. 1f inhibited gelatinase (MMP-9) activity in a concentration-dependent manner, while 4b showed no effect suggesting different mechanisms for inhibition of cell invasion. Signaling studies further highlighted these differences, showing that pyrazole compounds completely inhibited ERK phosphorylation and impaired HIF1α and NF-κB signaling, while pyrrolidinone and piperidinone (3 and 4b) had no effect. Annexin V staining suggested that the effect of pyrazole-based 1f on proliferation was due to cell killing through an apoptotic mechanism. PMID:24115356

  9. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.

    PubMed

    LeBeau, Aaron M; Sevillano, Natalia; King, Mandy L; Duriseti, Sai; Murphy, Stephanie T; Craik, Charles S; Murphy, Laura L; VanBrocklin, Henry F

    2014-01-01

    Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications. PMID:24505235

  10. Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation.

    PubMed

    Cunningham, Orla; Campion, Suzanne; Perry, V Hugh; Murray, Carol; Sidenius, Nicolai; Docagne, Fabian; Cunningham, Colm

    2009-12-01

    The urokinase plasminogen activator (uPA) receptor (uPAR) is a GPI-linked cell surface protein that facilitates focused plasmin proteolytic activity at the cell surface. uPAR has been detected in macrophages infiltrating the central nervous system (CNS) and soluble uPAR has been detected in the cerebrospinal fluid during a number of CNS pathologies. However, its expression by resident microglial cells in vivo remains uncertain. In this work, we aimed to elucidate the murine CNS expression of uPAR and uPA as well as that of tissue plasminogen activator and plasminogen activator inhibitor 1 (PAI-1) during insults generating distinct and well-characterized inflammatory responses; acute intracerebral lipopolysaccharide (LPS), acute kainate-induced neurodegeneration, and chronic neurodegeneration induced by prion disease inoculation. All three insults induced marked expression of uPAR at both mRNA and protein level compared to controls (naïve, saline, or control inoculum-injected). uPAR expression was microglial in all cases. Conversely, uPA transcription and activity was only markedly increased during chronic neurodegeneration. Dissociation of uPA and uPAR levels in acute challenges is suggestive of additional proteolysis-independent roles for uPAR. PAI-1 was most highly expressed upon LPS challenge, whereas tissue plasminogen activator mRNA was constitutively present and less responsive to all insults studied. These data are novel and suggest much wider involvement of the uPAR/uPA system in CNS function and pathology than previously supposed. PMID:19459212

  11. Urokinase-type plasminogen activator receptor modulates epileptogenesis in mouse model of temporal lobe epilepsy.

    PubMed

    Ndode-Ekane, Xavier Ekolle; Pitkänen, Asla

    2013-06-01

    Mutation in Plaur gene encoding urokinase-type plasminogen activator receptor (uPAR) results in epilepsy and autistic phenotype in mice. In humans, a single nucleotide polymorphism in PLAUR gene represents a risk for autism spectrum disorders. Importantly, the expression of uPAR is elevated in the brain after various epileptogenic insults like traumatic brain injury and status epilepticus. So far, the consequences of altered uPAR expression on brain networks are poorly known. We tested a hypothesis that uPAR regulates post-injury neuronal reorganization and consequent functional outcome, particularly epileptogenesis. Epileptogenesis was induced by intrahippocampal injection of kainate in adult male wild type (Wt) or uPAR knockout (uPAR-/-) mice, and animals were monitored with continuous (24/7) video-electroencephalogram for 30 days. The severity of status epilepticus did not differ between the genotypes. The spontaneous electrographic seizures which developed were, however, longer and their behavioral manifestations were more severe in uPAR-/- than Wt mice. The more severe epilepsy phenotype in uPAR-/- mice was associated with delayed but augmented inflammatory response and more severe neurodegeneration in the hippocampus. Also, the distribution of newly born cells in the dentate gyrus was more scattered, and the recovery of hippocampal blood vessel length from status epilepticus-induced damage was compromised in uPAR-/- mice as compared to Wt mice. Our data demonstrate that a deficiency in uPAR represents a mechanisms which results in the development of a more severe epilepsy phenotype and progressive brain pathology after status epilepticus. We suggest that uPAR represents a rational target for disease-modifying treatments after epileptogenic brain insults. PMID:23263886

  12. Urokinase-coated chitosan nanoparticles for thrombolytic therapy: preparation and pharmacodynamics in vivo.

    PubMed

    Jin, Hai-jiang; Zhang, Hao; Sun, Min-li; Zhang, Bai-gen; Zhang, Ji-wei

    2013-11-01

    Blood reperfusion of affected limbs is the most effective therapy for peripheral vascular thrombotic disease, restoring nutrition and blood flow to threatened tissues. Because it is more cost-effective than other thrombolytics, urokinase (UK) is widely used to treat venous thrombosis in China. However, its use is limited because of the risk of UK-related hemorrhagic complications. UK-coated nanoparticles (NPs) may decrease adverse effects while simultaneously increasing thrombolytic benefits. The aim of this study was to combine the sustained-release properties of NPs with the clinical benefits of catheter-directed thrombolysis (CDT) to create a promising new therapy. NPs were prepared via self-assembled chitosan and tripolyphosphate, introduced into a thrombosis model in New Zealand white rabbits, and the ratio of the residual thrombus cross-sectional area to the vascular cross-sectional area was calculated. The NPs had a drug-bearing efficiency of 14.5 ± 1.3%, an encapsulation efficiency of 94.8 ± 2.1% while the particle size of UK-coated NPs was 236 nm. Transmission electron microscopy results showed that the shape of the NPs were spherical and regular. Whether delivered by intravenation or catheter, UK-coated NPs produced a significant increase in the thrombolytic effect compared with free UK and confirmed the superiority of CDT for improving clot lysis over drug-induced systemic thrombolysis. The intravenous NPs caused an abnormal increase in fibrinogen. In conclusion, a water-soluble UK-WCS-NP suspension with good encapsulation efficiency was easily prepared UK-WCS-NPs were capable of maintaining UK activity, provided sustained-release of UK and exhibited better thrombolytic function than free UK. PMID:23728739

  13. Cytokines in cerebrospinal fluid of neurosyphilis patients: Identification of Urokinase plasminogen activator using antibody microarrays.

    PubMed

    Lu, Ping; Zheng, Dao-Cheng; Fang, Chang; Huang, Jin-Mei; Ke, Wu-Jian; Wang, Liu-Yuan; Zeng, Wei-Ying; Zheng, He-Ping; Yang, Bin

    2016-04-15

    Little is known regarding protein responses to syphilis infection in cerebrospinal fluid (CSF) of patients presenting with neurosyphilis. Protein and antibody arrays offer a new opportunity to gain insights into global protein expression profiles in these patients. Here we obtained CSF samples from 46 syphilis patients, 25 of which diagnosed as having central nervous system involvement based on clinical and laboratory findings. The CSF samples were then analyzed using a RayBioH L-Series 507 Antibody Array system designed to simultaneously analyze 507 specific cytokines. The results indicated that 41 molecules showed higher levels in patients with neurosyphilis in comparison with patients without neural involvement. For validation by single target ELISA, we selected five of them (MIP-1a, I-TAC/CXCL11, Urokinase plasminogen activator [uPA], and Oncostatin M) because they have previously been found to be involved in central nervous system (CNS) disorders. The ELISA tests confirmed that uPA levels were significantly higher in the CSF of neurosyphilis patients (109.1±7.88pg/ml) versus patients without CNS involvement (63.86±4.53pg/ml, p<0.0001). There was also a clear correlation between CSF uPA levels and CSF protein levels (p=0.0128) as well as CSF-VDRL titers (p=0.0074) used to diagnose neurosyphilis. No significant difference between the two groups of patients, however, was found in uPA levels in the serum, suggesting specific activation of the inflammatory system in the CNS but not the periphery in neurosyphilis patients. We conclude that measurements of uPA levels in CSF may be an additional parameter for diagnosing neurosyphilis. PMID:27049560

  14. Effect of urokinase-type plasminogen activator system in gastric cancer with peritoneal metastasis

    PubMed Central

    DING, YOUCHENG; ZHANG, HUI; LU, AIGUO; ZHOU, ZHUQING; ZHONG, MINGAN; SHEN, DONGWEI; WANG, XUJING; ZHU, ZHENGGANG

    2016-01-01

    Peritoneal metastasis is a primary cause of mortality in patients with gastric cancer. Urokinase-type plasminogen activator (uPA) has been demonstrated to be associated with tumor cell metastasis through the degradation of the extracellular matrix. The present study aimed to investigate the mechanisms of the uPA system in gastric cancer with peritoneal metastasis. Expression of uPA, uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) in four gastric cell lines (AGS, SGC7901, MKN45 and MKN28) was measured by semiquantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting. uPA activity was detected using a uPA activity kit. Peritoneal implantation models of rats were established by injecting four gastric cancer cell lines for the selection of the cancer cells with a high planting potential. Biological behaviors, including adhesion, migration and invasion, were determined using a methyl thiazolyl tetrazolium assay. Expression of the uPA system was observed to be highest in the SGC7901 cells among the four gastric cell lines. uPA activity was observed to be highest in the MKN45 cells and lowest in the AGS cells. Furthermore, peritoneal implantation analysis demonstrated that no peritoneal tumors were identified in the AGS cells, whilst the tumor masses observed in the SGC7901 and MKN45 cells were of different sizes. The survival times of the rats injected with the MKN28 and SGC7901 cells were longer than those of the rats injected with the MKN45 cells. Antibodies for uPA, uPAR and PAI-1 in the uPA system had the ability to inhibit the adhesion, migration and invasion of peritoneal metastasis in the gastric cancer cells. The results of the present study demonstrated that the uPA system was positively associated with peritoneal metastasis in gastric cancer. PMID:27313768

  15. Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

    PubMed Central

    Zha, Xueqiang; Diaz, Ricardo; Franco, Jose Javier Rosado; Sanchez, Veronica Forbes; Fasoli, Ezio; Barletta, Gabriel; Carvajal, Augusto; Bansal, Vibha

    2014-01-01

    In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC50 values. The chloroform extract showed the lowest IC50 value (3.52 μg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study. PMID:23896619

  16. Visualization of hepatic arteries with 3D ultrasound during intra-arterial therapies

    NASA Astrophysics Data System (ADS)

    Gérard, Maxime; Tang, An; Badoual, Anaïs.; Michaud, François; Bigot, Alexandre; Soulez, Gilles; Kadoury, Samuel

    2016-03-01

    Liver cancer represents the second most common cause of cancer-related mortality worldwide. The prognosis is poor with an overall mortality of 95%. Moreover, most hepatic tumors are unresectable due to their advanced stage at discovery or poor underlying liver function. Tumor embolization by intra-arterial approaches is the current standard of care for advanced cases of hepatocellular carcinoma. These therapies rely on the fact that the blood supply of primary hepatic tumors is predominantly arterial. Feedback on blood flow velocities in the hepatic arteries is crucial to ensure maximal treatment efficacy on the targeted masses. Based on these velocities, the intra-arterial injection rate is modulated for optimal infusion of the chemotherapeutic drugs into the tumorous tissue. While Doppler ultrasound is a well-documented technique for the assessment of blood flow, 3D visualization of vascular anatomy with ultrasound remains challenging. In this paper we present an image-guidance pipeline that enables the localization of the hepatic arterial branches within a 3D ultrasound image of the liver. A diagnostic Magnetic resonance angiography (MRA) is first processed to automatically segment the hepatic arteries. A non-rigid registration method is then applied on the portal phase of the MRA volume with a 3D ultrasound to enable the visualization of the 3D mesh of the hepatic arteries in the Doppler images. To evaluate the performance of the proposed workflow, we present initial results from porcine models and patient images.

  17. Hepatic artery injury during left hepatic trisectionectomy for colorectal liver metastasis treated by portal vein arterialization

    PubMed Central

    Hokuto, Daisuke; Nomi, Takeo; Yamato, Ichiro; Yasuda, Satoshi; Obara, Shinsaku; Yamada, Takatsugu; Kanehiro, Hiromichi; Nakajima, Yoshiyuki

    2015-01-01

    Portal vein arterialization (PVA) has been applied as a salvage procedure in hepatopancreatobiliary surgeries, including transplantation and liver resection, with revascularization for malignancies. Here we describe the use PVA as a salvage procedure following accidental injury of the hepatic artery to the remnant liver occurred during left hepatic trisectionectomy for colorectal liver metastases (CRLM). A 60-year-old man with cancer of the sigmoid colon and initially unresectable CRLM received 11 cycles of hepatic arterial infusion chemotherapy with 5-fluorouracil (1500 mg/week), after which CRLM was downstaged to resectable. One month after laparoscopic sigmoidectomy, a left trisectionectomy and wedge resection of segment 6 were performed. The posterior branch of the right hepatic artery, the only feeding artery to the remnant liver, was injured and totally dissected. Because microsurgical reconstruction of the artery was impossible, PVA was used; PVA is the sole known procedure available when hepatic artery reconstruction is impossible. The patient then suffered portal hypertension, and closure of arterio-portal anastomosis using an interventional technique with angiography was eventually performed on postoperative day 73. Therefore, it is considered that because PVA is associated with severe postoperative portal hypertension, closure of the arterio-portal shunt should be performed as soon as possible on diagnosing portal hypertension. PMID:26197094

  18. Hepatic artery injury during left hepatic trisectionectomy for colorectal liver metastasis treated by portal vein arterialization.

    PubMed

    Hokuto, Daisuke; Nomi, Takeo; Yamato, Ichiro; Yasuda, Satoshi; Obara, Shinsaku; Yamada, Takatsugu; Kanehiro, Hiromichi; Nakajima, Yoshiyuki

    2015-01-01

    Portal vein arterialization (PVA) has been applied as a salvage procedure in hepatopancreatobiliary surgeries, including transplantation and liver resection, with revascularization for malignancies. Here we describe the use PVA as a salvage procedure following accidental injury of the hepatic artery to the remnant liver occurred during left hepatic trisectionectomy for colorectal liver metastases (CRLM). A 60-year-old man with cancer of the sigmoid colon and initially unresectable CRLM received 11 cycles of hepatic arterial infusion chemotherapy with 5-fluorouracil (1500mg/week), after which CRLM was downstaged to resectable. One month after laparoscopic sigmoidectomy, a left trisectionectomy and wedge resection of segment 6 were performed. The posterior branch of the right hepatic artery, the only feeding artery to the remnant liver, was injured and totally dissected. Because microsurgical reconstruction of the artery was impossible, PVA was used; PVA is the sole known procedure available when hepatic artery reconstruction is impossible. The patient then suffered portal hypertension, and closure of arterio-portal anastomosis using an interventional technique with angiography was eventually performed on postoperative day 73. Therefore, it is considered that because PVA is associated with severe postoperative portal hypertension, closure of the arterio-portal shunt should be performed as soon as possible on diagnosing portal hypertension. PMID:26197094

  19. Cerebral blood flow with the continuous infusion of oxygen-15-labeled water

    SciTech Connect

    Jones, S.C.; Greenberg, J.H.; Dann, R.; Robinson, G.D. Jr.; Kushner, M.; Alavi, A.; Reivich, M.

    1985-12-01

    This work describes the determination of CBF in eight normal human subjects with positron emission tomographic (PET) imaging using the continuous intravenous infusion of H2(15)O. A whole-brain CBF model is described that permits the comparison of the CBF values determined using PET with those obtained using other methods. This model includes a correction for whole-brain recovery coefficient, a correction for the underestimation of flow due to the nonlinearity of the CBF model when considering tissue that includes both gray and white matter, the use of in vitro-determined brain-blood partition coefficients for gray and white matter, and a variation of the equilibrium model that permits the arterial concentration to vary. CBF values using this method compare well with values determined previously. Regional determinations using a brain overlay atlas are presented. Radiation dosimetry for the continuous infusion of H2(15)O is also included.

  20. Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin

    NASA Technical Reports Server (NTRS)

    Morrow, B. A.; Keil, L. C.; Severs, W. B.

    1992-01-01

    Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

  1. Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

    PubMed Central

    Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

    2014-01-01

    Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity. PMID:25421476

  2. Placement of tibial intraosseous infusion devices.

    PubMed

    Harcke, H Theodore; Crawley, Geoffrey; Mabry, Robert; Mazuchowski, Edward

    2011-07-01

    Post-mortem preautopsy multidetector computed tomography was used to assess the placement of tibial intraosseous infusion needles in 52 cases of battlefield trauma deaths for which medical intervention included the use of the technique. In 58 (95%) of 61 needles, the tip was positioned in medullary bone. All 3 (5%) unsuccessful placements were in the left leg, and the needle was not directed perpendicular to the medial tibial cortex as recommended. Considering the nature of military trauma and the environmental conditions under which care is rendered, military medical personnel appear to be highly successful in the placement of tibial intraosseous infusion needles. PMID:22128726

  3. Cultural Congruence and Infusion Nursing Practice.

    PubMed

    Abitz, Tracey L

    2016-01-01

    The importance of cultural competence in every nursing practice setting in today's world cannot be understated. Unconscious bias can have detrimental effects on therapeutic relationships and health outcomes. Nursing models of cultural competence by Purnell, Leininger, and Campinha-Bacote are reviewed. The Kleinman Model and LEARN Model offer questions and guidelines to facilitate assessment of patients' understanding of illness and treatment. The Infusion Nursing Standards of Practice contains elements of diversity and cultural competence throughout. Self-reflection of one's own values, beliefs, biases, and practice as an infusion nurse will promote the development of cultural competence. PMID:26934161

  4. Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats

    PubMed Central

    Damiani, Elisa; Ince, Can; Orlando, Fiorenza; Pierpaoli, Elisa; Cirioni, Oscar; Giacometti, Andrea; Mocchegiani, Federico; Pelaia, Paolo; Provinciali, Mauro; Donati, Abele

    2016-01-01

    Background Sepsis-induced microcirculatory alterations contribute to tissue hypoxia and organ dysfunction. In addition to its plasma volume expanding activity, human serum albumin (HSA) has anti-oxidant and anti-inflammatory properties and may have a protective role in the microcirculation during sepsis. The concentration of HSA infused may influence these effects. We compared the microcirculatory effects of the infusion of 4% and 20% HSA in an experimental model of sepsis. Methods Adult male Wistar rats were equipped with arterial and venous catheters and received an intravenous infusion of lipopolysaccharide (LPS, serotype O127:B8, 10 mg/kg over 30 minutes) or vehicle (SHAM, n = 6). Two hours later, endotoxemic animals were randomized to receive 10 mL/kg of either 4% HSA (LPS+4%HSA, n = 6), 20% HSA (LPS+20%HSA, n = 6) or 0.9% NaCl (LPS+0.9%NaCl, n = 6). No fluids were given to an additional 6 animals (LPS). Vessel density and perfusion were assessed in the skeletal muscle microcirculation with sidestream dark field videomicroscopy at baseline (t0), 2 hours after LPS injection (t1), after HSA infusion (t2) and 1 hour later (t3). The mean arterial pressure (MAP) and heart rate were recorded. Serum endothelin-1 was measured at t2. Results MAP was stable over time in all groups. The microcirculatory parameters were significantly altered in endotoxemic animals at t1. The infusion of both 4% and 20% HSA similarly increased the perfused vessel density and blood flow velocity and decreased the flow heterogeneity to control values. Microvascular perfusion was preserved in the LPS+20%HSA group at t3, whereas alterations reappeared in the LPS+4%HSA group. Conclusions In a rat model of normotensive endotoxemia, the infusion of 4% or 20% HSA produced a similar acute improvement in the microvascular perfusion in otherwise unresuscitated animals. PMID:26942605

  5. Design, Synthesis, Biochemical Studies, Cellular Characterization, and Structure-Based Computational Studies of Small Molecules Targeting the Urokinase Receptor

    PubMed Central

    Wang, Fang; Knabe, W. Eric; Li, Liwei; Jo, Inha; Mani, Timmy; Roehm, Hartmut; Oh, Kyungsoo; Li, Jing; Khanna, May; Meroueh, Samy O.

    2012-01-01

    The urokinase receptor (uPAR) serves as a docking site to the serine protease urokinase-type plasminogen activator (uPA) to promote extracellular matrix (ECM) degradation and tumor invasion and metastasis. Previously, we had reported a small molecule inhibitor of the uPAR•uPA interaction that emerged from structure-based virtual screening. Here, we measure the affinity of a large number of derivatives from commercial sources. Synthesis of additional compounds was carried out to probe the role of various groups on the parent compound. Extensive structure-based computational studies suggested a binding mode for these compounds that led to a structure-activity relationship study. Cellular studies in non-small cell lung cancer (NSCLC) cell lines that include A549, H460 and H1299 showed that compounds blocked invasion, migration and adhesion. The effects on invasion of active compounds were consistent with their inhibition of uPA and MMP proteolytic activity. These compounds showed weak cytotoxicity consistent with the confined role of uPAR to metastasis. PMID:22771232

  6. Relationship between urokinase plasminogen activator receptor (uPAR) and the invasion of human prenatal hair follicle.

    PubMed

    Gao, Qiangguo; Fu, Gang; Huang, Gang; Lian, Xiaohua; Yu, Jin; Yang, Tian

    2010-08-01

    During the morphogenesis of hair follicles, the invasive migration of basal keratinocytes resembles cell's dissemination of tissue remodeling. The urokinase-type plasminogen activator receptor (uPAR) appears to be a key molecule in the metastasis. In order to elucidate the relationship between uPAR and the invasion of the human hair follicle, immunohistochemistry, RT-PCR, plasmids transfection, and western blot were used. The results showed that uPAR was expressed in the outermost epithelial cells of the hair follicle and the basal keratinocytes of epidermis, and that the expression decreased with the development of the hair follicle. The cells of the outer root sheath (ORS) and interfollicle epidermis, which overexpressed uPAR, acquired increased invasiveness; however, they showed decreased invasion with overexpression of the urokinase-type plasminogen activator amino terminal fragment (uPA ATF), which inhibited the combination of uPAR and uPA competitively, and the cell invasive migration with overexpressed uPAR was required activated extracellular signal-regulated kinases (ERK). These results implied that overexpression of uPAR promote the invasive migration of hair follicle into the dermis in uPA-dependent and independent manner during human prenatal development. PMID:20012874

  7. The tyrosine phosphatase SHP-2 controls urokinase-dependent signaling and functions in human vascular smooth muscle cells

    SciTech Connect

    Kiyan, Julia Haller, Hermann; Dumler, Inna

    2009-04-01

    The urokinase (uPA)/urokinase receptor (uPAR) multifunctional system is an important mediator of functional behaviour of human vascular smooth muscle cells (VSMC). uPAR associates with platelet-derived growth factor receptor {beta} (PDGFR-{beta}), which serves as a transmembrane adaptor for uPAR in VSMC, to transduce intracellular signaling and initiate functional changes. The precise and rapid propagation of these signaling cascades demands both strict and flexible regulatory mechanisms that remain unexplored. We provide evidence that the tyrosine phosphatase SHP-2 mediates these processes. uPA regulated SHP-2 phosphorylation, catalytic activity, and its co-localization and association with the PDGFR-{beta}. Active PDGFR-{beta} was required for the uPA-induced SHP-2 phosphorylation. uPAR-directed STAT1 pathway was disturbed in cells expressing SHP-2 inactive mutant. Both, cell proliferation and migration were impaired in VSMC with downregulated SHP-2. Elucidating the underlying mechanisms, we found that uPA induced SHP-2 recruitment to lipid rafts. Disruption of rafts abolished uPA-related control of SHP-2 phosphorylation, its association with PDGFR-{beta} and finally the VSMC functional responses. Our results demonstrate that SHP-2 plays an important role in uPA-directed signaling and functional control of human VSMC and suggest that this phosphatase might contribute to the pathogenesis of the uPA-related vascular remodeling.

  8. Altered expression of urokinase-type plasminogen activator and plasminogen activator inhibitor in high-risk soft tissue sarcomas.

    PubMed

    Benassi, M S; Ponticelli, F; Azzoni, E; Gamberi, G; Pazzaglia, L; Chiechi, A; Conti, A; Spessotto, P; Scapolan, M; Pignotti, E; Bacchini, P; Picci, P

    2007-09-01

    In recent years, classification of soft-tissue sarcomas (STS) has improved with cytogenetic analyses, but their clinical behavior is still not easily predictable. The aim of this study was to detect alterations in the urokinase-type plasminogen system, involved in tumor growth and invasion, by comparing mRNA levels of its components with those of paired normal tissues, and relating them with patient clinical course. Real-time PCR was performed on human STS cell lines and tissues from highly malignant STS, including leiomyosarcomas and malignant fibrous histiocytomas, to evaluate the expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of gene products was also performed. Median mRNA values of all genes studied were higher in tumors than in paired normal tissues. In agreement with data on STS cell lines, significant up-regulation for uPA and PAI-1 genes compared to reference values was seen. Moreover, different levels of expression were related to histotype and metastatic phenotype. There was accordance between uPA mRNA and protein expression, while immunodetection of PAI-1 product was weak and scattered. Clearly, the controversial role of PAI-1 protein requires further biological analyses, but evident involvement of uPA/PAI-1 gene overexpression in STS malignancy may highlight a molecular defect useful in discriminating STS high-risk patients. PMID:17523079

  9. "The home infusion patient": patient profiles for the home infusion therapy market.

    PubMed

    Westbrook, K W; Powers, T

    1999-01-01

    The authors review the relevant literature regarding home health care patient profiles. An empirical analysis is provided from archival data for a home infusion company servicing patients in urban and rural areas. The results are provided as a 2 x 2 matrix for patients in urban and rural areas seeing either a specialist or primary care physicians. A series of moderated regressions indicate that type of treating physician, patient's gender, geographic residence and level of acuity are cogent in predicting the complexity of prescribed infusion therapies. Managerial implications are provided for the home care marketer in segmenting patient markets for infusion services. PMID:10538737

  10. Effects of volume resuscitation on splanchnic perfusion in canine model of severe sepsis induced by live Escherichia coli infusion

    PubMed Central

    Lagoa, Claudio Esteves; de Figueiredo, Luiz Francisco Poli; Cruz, Ruy Jorge; Silva, Eliézer; Rocha e Silva, Maurício

    2004-01-01

    Introduction We conducted the present study to investigate whether early large-volume crystalloid infusion can restore gut mucosal blood flow and mesenteric oxygen metabolism in severe sepsis. Methods Anesthetized and mechanically ventilated male mongrel dogs were challenged with intravenous injection of live Escherichia coli (6 × 109 colony-forming units/ml per kg over 15 min). After 90 min they were randomly assigned to one of two groups – control (no fluids; n = 13) or lactated Ringer's solution (32 ml/kg per hour; n = 14) – and followed for 60 min. Cardiac index, mesenteric blood flow, mean arterial pressure, systemic and mesenteric oxygen-derived variables, blood lactate and gastric carbon dioxide tension (PCO2; by gas tonometry) were assessed throughout the study. Results E. coli infusion significantly decreased arterial pressure, cardiac index, mesenteric blood flow, and systemic and mesenteric oxygen delivery, and increased arterial and portal lactate, intramucosal PCO2, PCO2 gap (the difference between gastric mucosal and arterial PCO2), and systemic and mesenteric oxygen extraction ratio in both groups. The Ringer's solution group had significantly higher cardiac index and systemic oxygen delivery, and lower oxygen extraction ratio and PCO2 gap at 165 min as compared with control animals. However, infusion of lactated Ringer's solution was unable to restore the PCO2 gap. There were no significant differences between groups in mesenteric oxygen delivery, oxygen extraction ratio, or portal lactate at the end of study. Conclusion Significant disturbances occur in the systemic and mesenteric beds during bacteremic severe sepsis. Although large-volume infusion of lactated Ringer's solution restored systemic hemodynamic parameters, it was unable to correct gut mucosal PCO2 gap. PMID:15312221

  11. Measuring glycerol turnover, gluconeogenesis from glycerol, and total gluconeogenesis with [2-13C] glycerol: role of the infusion-sampling mode.

    PubMed

    Peroni, O; Large, V; Odeon, M; Beylot, M

    1996-07-01

    Mass isotopomer distribution analysis (MIDA) of glucose during infusion of [2-13C]glycerol is a new method for measuring total gluconeogenesis (GNG). Since this method relies on calculation of the isotopic enrichment (IE) of hepatic triose phosphates (TP), the results should be independent of the sites of tracer infusion and blood sampling. Postabsorptive and starved rats were infused with [2-13C]glycerol and sampled either in the arterial-venous (A-V) or venous-arterial (V-A) modes. Blood was also sampled from the portal vein. In both postabsorptive and starved rats, glycerol turnover rate (Rt) and the percent contribution of glycerol to total glucose production were higher in the A-V mode than in the V-A mode (P < .05). Glycerol IE in portal venous blood was intermediate between IE values observed in peripheral arterial and venous blood. Its use for calculating the contribution of glycerol to glucose production reconciled the results obtained with the two infusion-sampling modes in both postabsorptive and starved rats; this contribution was increased by starvation (P < .01). In postabsorptive rats, total GNG calculated from MIDA of glucose accounted for approximately 50% of glucose production whatever the infusion-sampling mode (A-V, 48.8% +/- 4.7%; V-A, 52.2% +/- 3.9%). This contribution increased to 90% in starved rats, again, with no difference between A-V (95.2% +/- 1.8%) and V-A (89.2% +/- 1.3%) modes. In conclusion, during infusion of [2-13C]glycerol, total GNG measured from MIDA of glucose is independent of the infusion-sampling mode, contrary to calculations of Rt and GNG from glycerol. Measurement of glycerol IE in portal venous blood reconciles the results obtained with the two modes with respect to the contribution of glycerol to GNG. PMID:8692028

  12. Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence.

    PubMed Central

    Chiaradonna, F; Fontana, L; Iavarone, C; Carriero, M V; Scholz, G; Barone, M V; Stoppelli, M P

    1999-01-01

    Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed. U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo. PMID:10357814

  13. The NASA SARP Software Research Infusion Initiative

    NASA Technical Reports Server (NTRS)

    Hinchey, Mike; Pressburger, Tom; Markosian, Lawrence; Feather, Martin

    2006-01-01

    A viewgraph presentation describing the NASA Software Assurance Research Program (SARP) research infusion projects is shown. The topics include: 1) Background/Motivation; 2) Proposal Solicitation Process; 3) Proposal Evaluation Process; 4) Overview of Some Projects to Date; and 5) Lessons Learned.

  14. A Telecommunications-Infused Community Action Project.

    ERIC Educational Resources Information Center

    March, Thomas; Puma, Jessica

    1996-01-01

    The Nonprofit Prophets, a telecommunications-infused community action project, was designed for high school students. Students were teamed with a nonprofit organization and produced videoconferences or Web sites for them. Although specific skills were acquired, students also gained confidence and self-esteem as well as a belief that they…

  15. Infusing Earth Systems Concepts throughout the Curriculum.

    ERIC Educational Resources Information Center

    Fortner, Rosanne W.; Boyd, Sally

    The Program for Leadership in Earth Systems Education (PLESE), a teacher enhancement program sponsored by the National Science Foundation in 1990-94, was a coordinated effort to infuse Earth Systems concepts throughout the K-12 science curriculum across the United States. Characteristics of the program are reviewed in this paper and the results of…

  16. Multiple Intravenous Infusions Phase 1b

    PubMed Central

    Cassano-Piché, A; Fan, M; Sabovitch, S; Masino, C; Easty, AC

    2012-01-01

    Background Minimal research has been conducted into the potential patient safety issues related to administering multiple intravenous (IV) infusions to a single patient. Previous research has highlighted that there are a number of related safety risks. In Phase 1a of this study, an analysis of 2 national incident-reporting databases (Institute for Safe Medical Practices Canada and United States Food and Drug Administration MAUDE) found that a high percentage of incidents associated with the administration of multiple IV infusions resulted in patient harm. Objectives The primary objectives of Phase 1b of this study were to identify safety issues with the potential to cause patient harm stemming from the administration of multiple IV infusions; and to identify how nurses are being educated on key principles required to safely administer multiple IV infusions. Data Sources and Review Methods A field study was conducted at 12 hospital clinical units (sites) across Ontario, and telephone interviews were conducted with program coordinators or instructors from both the Ontario baccalaureate nursing degree programs and the Ontario postgraduate Critical Care Nursing Certificate programs. Data were analyzed using Rasmussen’s 1997 Risk Management Framework and a Health Care Failure Modes and Effects Analysis. Results Twenty-two primary patient safety issues were identified with the potential to directly cause patient harm. Seventeen of these (critical issues) were categorized into 6 themes. A cause-consequence tree was established to outline all possible contributing factors for each critical issue. Clinical recommendations were identified for immediate distribution to, and implementation by, Ontario hospitals. Future investigation efforts were planned for Phase 2 of the study. Limitations This exploratory field study identifies the potential for errors, but does not describe the direct observation of such errors, except in a few cases where errors were observed. Not all

  17. 21 CFR 526.1590 - Novobiocin infusion.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... strains of Staphylococcus aureus. (iii) Limitations. Do not milk for at least 6 hours after treatment... is used in dry cows for the treatment of mastitis caused by susceptible strains of Staphylococcus aureus and Streptococcus agalactiae. (iii) Limitations. Infuse each quarter at the time of drying...

  18. Infusing Catholic Identity throughout the Campus Community

    ERIC Educational Resources Information Center

    Miller, Amata

    2011-01-01

    This article, originally presented as a plenary address at the Association of Catholic Colleges and Universities 2011 Annual Meeting, addresses a bottom-up methodology for infusing the spirit of Catholic identity more deeply throughout a campus community. The author begins with an exploration of some theoretical underpinnings of this approach and…

  19. Local hindlimb antioxidant infusion does not affect muscle glucose uptake during in situ contractions in rat.

    PubMed

    Merry, T L; Dywer, R M; Bradley, E A; Rattigan, S; McConell, G K

    2010-05-01

    There is evidence that reactive oxygen species (ROS) contribute to the regulation of skeletal muscle glucose uptake during highly fatiguing ex vivo contraction conditions via AMP-activated protein kinase (AMPK). In this study we investigated the role of ROS in the regulation of glucose uptake and AMPK signaling during low-moderate intensity in situ hindlimb muscle contractions in rats, which is a more physiological protocol and preparation. Male hooded Wistar rats were anesthetized, and then N-acetylcysteine (NAC) was infused into the epigastric artery (125 mg.kg(-1).h(-1)) of one hindlimb (contracted leg) for 15 min before this leg was electrically stimulated (0.1-ms impulse at 2 Hz and 35 V) to contract at a low-moderate intensity for 15 min. The contralateral leg did not receive stimulation or local NAC infusion (rest leg). NAC infusion increased (P<0.05) plasma cysteine and cystine (by approximately 360- and 1.4-fold, respectively) and muscle cysteine (by 1.5-fold, P=0.001). Although contraction did not significantly alter muscle tyrosine nitration, reduced (GSH) or oxidized glutathione (GSSG) content, S-glutathionylation of protein bands at approximately 250 and 150 kDa was increased (P<0.05) approximately 1.7-fold by contraction, and this increase was prevented by NAC. Contraction increased (P<0.05) skeletal muscle glucose uptake 20-fold, AMPK phosphorylation 6-fold, ACCbeta phosphorylation 10-fold, and p38 MAPK phosphorylation 60-fold, and the muscle fatigued by approximately 30% during contraction and NAC infusion had no significant effect on any of these responses. This was despite NAC preventing increases in S-glutathionylation with contraction. In conclusion, unlike during highly fatiguing ex vivo contractions, local NAC infusion during in situ low-moderate intensity hindlimb contractions in rats, a more physiological preparation, does not attenuate increases in skeletal muscle glucose uptake or AMPK signaling. PMID:20203065

  20. Characterization of the murine plasminogen/urokinase-type plasminogen-activator system.

    PubMed

    Lijnen, H R; Van Hoef, B; Collen, D

    1996-11-01

    The murine plasminogen/urokinase-type plasminogen-activator (u-PA) system was studied using purified proteins, plasma and endothelioma cells. Recombinant murine u-PA was obtained as a single-chain molecule of 45 kDa which was converted to two-chain u-PA with plasmin by cleavage of the Lys159-Ile160 peptide bond. Murine plasminogen, purified from plasma as a single-chain protein of 95 kDa, was resistant to quantitative activation with murine recombinant two-chain u-PA: only 15% activation within 1 h at 37 degrees C was obtained in mixtures of 1 microM plasminogen and 5 nM recombinant two-chain u-PA, whereas quantitative activation was observed in the autologous human system. Addition of 6-aminohexanoic acid to native murine plasminogen resulted in quantitative activation within 1 h. In murine plasma in vitro, plasminogen was also resistant to quantitative activation with u-PA (50% activation within 1 h at 37 degrees C with 50 nM recombinant two-chain u-PA, whereas in the human system nearly quantitative activation was obtained). Murine plasma clots submerged in murine plasma were resistant to lysis with u-PA; < or = 2% clot lysis in 2 h was obtained with 80 nM recombinant two-chain u-PA in the autologous murine system whereas 50% clot lysis in 2 h required only 15 nM recombinant two-chain u-PA in the autologous human system. Saturable binding of murine recombinant two-chain u-PA was observed to murine endothelioma cells that are genetically deficient in u-PA (u-PA-/- End cells). Binding was characterized by a Kd of 5.5 nM and 800000 binding sites/cell. However, u-PA-/- End cells did not significantly stimulate the activation rate of murine plasminogen by murine recombinant two-chain u-PA and did not enhance the plasmin-mediated conversion rate of murine recombinant single-chain u-PA to its two-chain derivative. Murine recombinant two-chain u-PA bound to murine endothelioma cells was quantitatively inhibited by murine plasminogen-activator inhibitor-1 (PAI-1). Thus

  1. High level of urokinase plasminogen activator contributes to cholangiocarcinoma invasion and metastasis

    PubMed Central

    Thummarati, Parichut; Wijitburaphat, Sitsom; Prasopthum, Aruna; Menakongka, Apaporn; Sripa, Banchob; Tohtong, Rutaiwan; Suthiphongchai, Tuangporn

    2012-01-01

    AIM: To investigate the role of urokinase plasminogen activator (uPA) in cholangiocarcinoma (CCA) invasion and its correlation with clinicopathological parameters. METHODS: uPA expression in CCA tissue was determined by immunohistochemistry. The level of uPA from two CCA cell lines (HuCCA-1 and KKU-M213) and a non-cancer immortalized cholangiocyte cell line (H69) was monitored by plasminogen-gelatin zymography and western blotting, whereas that of plasminogen activator inhibitor type 1 (PAI-1) protein and uPA receptor (uPAR) mRNA was monitored by western blotting and quantitative real-time reverse transcriptase polymerase chain reaction, respectively. Two independent methods were employed to suppress uPA function: a synthetic uPA inhibitor (B428) and silencing of uPA gene expression using siRNA. In vitro invasion of the uPA-disrupted cells was assessed by Matrigel-coated Transwell assay. RESULTS: The immunohistochemical study showed that 75.3% (131/174) of CCA tissues expressed uPA. High uPA expression was correlated with lymphatic invasion and metastasis of CCA patients. Plasminogen-gelatin zymography of the conditioned media and cell-surface eluates showed that both CCA cell lines, but not H69, expressed both secreted and membrane-bound forms of uPA. Although the two CCA cell lines, HuCCA-1 and KKU-M213, expressed a relatively high level of uPA and uPAR, the latter exhibited a much lower degree of in vitro invasiveness, correlating with a high expression of PAI-1 in the latter, but not in the former. Suppressing uPA function with a specific uPA inhibitor, B428, or with siRNA against uPA reduced in vitro invasiveness of KKU-M213 cells, demonstrating the requirement for uPA in the invasiveness of CCA cells. Therefore, our in vivo and in vitro studies suggest that uPA is an important requirement for the invasion process of CCA. CONCLUSION: uPA expression correlates with lymphatic invasion and metastasis in vivo and is required for CCA cell invasion in vitro

  2. Radiation-induced hypomethylation triggers urokinase plasminogen activator transcription in meningioma cells.

    PubMed

    Velpula, Kiran Kumar; Gogineni, Venkateswara Rao; Nalla, Arun Kumar; Dinh, Dzung H; Rao, Jasti S

    2013-02-01

    Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H(2)O(2) or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers u

  3. Radiation-Induced Hypomethylation Triggers Urokinase Plasminogen Activator Transcription in Meningioma Cells1

    PubMed Central

    Velpula, Kiran Kumar; Gogineni, Venkateswara Rao; Nalla, Arun Kumar; Dinh, Dzung H; Rao, Jasti S

    2013-01-01

    Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H2O2 or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers u

  4. Urine soluble urokinase-type plasminogen activator receptor levels correlate with proteinuria in Puumala hantavirus infection

    PubMed Central

    Outinen, Tuula K.; Mäkelä, Satu; Huttunen, Reetta; Mäenpää, Niina; Libraty, Daniel; Vaheri, Antti; Mustonen, Jukka; Aittoniemi, Janne

    2014-01-01

    Objectives Urokinase-type plasminogen activator receptor (uPAR) is upregulated during inflammation and known to bind to β3-integrins, receptors used by pathogenic hantaviruses to enter endothelial cells. It has been proposed that soluble uPAR (suPAR) is a circulating factor that causes focal segmental glomerulosclerosis and proteinuria by activating β3-integrin in kidney podocytes. Proteinuria is also a characteristic feature of hantavirus infections. The aim of this study was to evaluate the relation between urine suPAR levels and disease severity in acute Puumala hantavirus (PUUV) infection. Design A single-centre, prospective cohort study. Subjects and methods Urinary suPAR levels were measured twice during the acute phase and once during convalescence in 36 patients with serologically confirmed PUUV infection. Fractional excretion of suPAR (FE suPAR) and of albumin (FE alb) were calculated. Results The FE suPAR was significantly elevated during the acute phase of PUUV infection compared to the convalescent phase (median 3.2%, range 0.8–52.0%, vs. median 1.9%, range 1.0–5.8%, P = 0.005). Maximum FE suPAR was correlated markedly with maximum FE alb (r = 0.812, P < 0.001), and with several other variables that reflect disease severity. There was a positive correlation with the length of hospitalization (r = 0.455, P = 0.009) and maximum plasma creatinine level (r = 0.780, P < 0.001), and an inverse correlation with minimum urinary output (r = −0.411, P = 0.030). There was no correlation between FE suPAR and plasma suPAR (r = 0.180, P = 0.324). Conclusion Urinary suPAR is markedly increased during acute PUUV infection and is correlated with proteinuria. High urine suPAR level may reflect local production of suPAR in the kidney during the acute infection. PMID:24717117

  5. Propofol Infusion Syndrome in Refractory Status Epilepticus

    PubMed Central

    Hwang, Woo Sub; Gwak, Hye Min; Seo, Dae-Won

    2013-01-01

    Background and Purpose: Propofol is used for treating refractory status epilepticus, which has high rate of mortality. Propofol infusion syndrome is a rare but often fatal syndrome, characterized by lactic acidosis, lipidemia, and cardiac failure, associated with propofol infusion over prolonged periods of time. We investigated the clinical factors that characterize propofol infusion syndrome to know the risk of them in refractory status epilepticus. Methods: This retrospective observation study was conducted in Samsung medical center from Jan. 2005 to Dec. 2009. Thirty two patients (19 males, 13 females, aged between 16 and 64 years), with refractory status epilepsy were included. Their clinical findings and treatment outcomes were evaluated retrospectively. We divided our patients into established status epilepticus (ESE) and refractory status epilepticus (RSE). And then the patients with RSE was further subdivided into propofol treatment group (RSE-P) and the other anesthetics treatment group (RSE-O). We analyzed the clinical characteristics by comparison of the groups. Results: There were significant differences of hypotension and lipid change between ESE and RSE (p<0.05). However, there was no significant difference between RSE-P and RSE-O groups. The hospital days were longer in RSE than in ESE (p=0.012) and treatment outcome was also worse in RSE than in ESE (p=0.007) but there were no significant differences of hospital stays and treatment outcome between RSE-P and RSE-O. Conclusions: RSE is very critical disease with high mortality, which may show as many clinical changes as propofol infusion syndrome. Therefore propofol infusion syndrome might be considered as one of the clinical manifestations of RSE. PMID:24649467

  6. Infusion fluids contain harmful glucose degradation products

    PubMed Central

    Bryland, Anna; Broman, Marcus; Erixon, Martin; Klarin, Bengt; Lindén, Torbjörn; Friberg, Hans; Wieslander, Anders; Kjellstrand, Per; Ronco, Claudio; Carlsson, Ola

    2010-01-01

    Purpose Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients’ blood. Methods The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. Results All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. Conclusions These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients. Electronic supplementary material The online version of this article (doi:10.1007/s00134-010-1873-x) contains supplementary material, which is available to authorized users. PMID:20397009

  7. Intravenous infusions in chronic pain management.

    PubMed

    Kosharskyy, Boleslav; Almonte, Wilson; Shaparin, Naum; Pappagallo, Marco; Smith, Howard

    2013-01-01

    In the United States, millions of Americans are affected by chronic pain, which adds heavily to national rates of morbidity, mortality, and disability, with an ever-increasing prevalence. According to a 2011 report titled Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research by the Institute of Medicine of the National Academies, pain not only exacts its toll on people's lives but also on the economy with an estimated annual economic cost of at least $560 - 635 billion in health care costs and the cost of lost productivity attributed to chronic pain. Intravenous infusions of certain pharmacologic agents have been known to provide substantial pain relief in patients with various chronic painful conditions. Some of these infusions are better, and although not necessarily the first therapeutic choice, have been widely used and extensively studied. The others show promise, however are in need of further investigations. This article will focus on non-opiate intravenous infusions that have been utilized for chronic painful disorders such as fibromyalgia, neuropathic pain, phantom limb pain, post-herpetic neuralgia, complex regional pain syndromes (CRPS), diabetic neuropathy, and central pain related to stroke or spinal cord injuries. The management of patients with chronic pain conditions is challenging and continues to evolve as new treatment modalities are explored and tested. The following intravenous infusions used to treat the aforementioned chronic pain conditions will be reviewed: lidocaine, ketamine, phentolamine, dexmedetomidine, and bisphosphonates. This overview is intended to familiarize the practitioner with the variety of infusions for patients with chronic pain. It will not, however, be able to provide guidelines for their use due to the lack of sufficient evidence. PMID:23703410

  8. Hardening of the arteries

    MedlinePlus

    Atherosclerosis; Arteriosclerosis; Plaque buildup - arteries; Hyperlipidemia - atherosclerosis; Cholesterol - atherosclerosis ... Hardening of the arteries often occurs with aging. As you grow older, ... narrows your arteries and makes them stiffer. These changes ...

  9. Mesenteric artery ischemia

    MedlinePlus

    ... ischemia is often seen in people who have hardening of the arteries in other parts of the ... long-term (chronic) mesenteric artery ischemia caused by hardening of the arteries ( atherosclerosis ): Abdominal pain after eating ...

  10. Carotid Artery Disease

    MedlinePlus

    ... brain with blood. If you have carotid artery disease, the arteries become narrow, usually because of atherosclerosis. ... one of the causes of stroke. Carotid artery disease often does not cause symptoms, but there are ...

  11. Coronary artery disease

    MedlinePlus Videos and Cool Tools

    The coronary arteries supply blood to the heart muscle itself. Damage to or blockage of a coronary artery can result in injury to the heart. Normally, blood flows through a coronary artery unimpeded. However, a ...

  12. Carotid Artery Disease

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Carotid Artery Disease? Carotid artery disease is a disease in ... blood to your face, scalp, and neck. Carotid Arteries Figure A shows the location of the right ...

  13. Subcutaneous infusion in palliative care: a focus on the neria soft 90 infusion set.

    PubMed

    Gabriel, Janice

    2014-11-01

    Subcutaneous administration of medications and/or fluids can play a crucial part in supporting patients at home and thereby avoiding the need for hospitalisation. It is an area of patient care that has received little attention compared with other types of parenteral therapies. However, it is an effective and safe route for continuous administration for individuals requiring palliative care. Technological advancements have led to improved subcutaneous infusion devices, such as fine-gauge cannulae with integral sharps protection, as well as integral hypoallergenic dressings. These design features not only help to increase patient comfort but also minimise the potential for needlestick injuries, as well as providing the health professional with one sterile package containing all of the components needed to establish subcutaneous infusion. However, technological developments alone are insufficient to improve patient outcomes. Knowledge of the individual patient, together with their diagnosis and intended treatment, will influence the choice of subcutaneous infusion device, with the overall aim of minimising the potential for complications and improving comfort. This paper provides an overview of subcutaneous infusion, including the importance of patient assessment and the education and training needs of health professionals, and then focuses on one specific subcutaneous infusion device: the neria soft 90 infusion set. PMID:25426880

  14. S-nitrosothiols dilate the mesenteric artery more potently than the femoral artery by a cGMP and L-type calcium channel-dependent mechanism.

    PubMed

    Liu, Taiming; Schroeder, Hobe J; Zhang, Meijuan; Wilson, Sean M; Terry, Michael H; Longo, Lawrence D; Power, Gordon G; Blood, Arlin B

    2016-08-31

    S-nitrosothiols (SNOs) are metabolites of NO with potent vasodilatory activity. Our previous studies in sheep indicated that intra-arterially infused SNOs dilate the mesenteric vasculature more than the femoral vasculature. We hypothesized that the mesenteric artery is more responsive to SNO-mediated vasodilation, and investigated various steps along the NO/cGMP pathway to determine the mechanism for this difference. In anesthetized adult sheep, we monitored the conductance of mesenteric and femoral arteries during infusion of S-nitroso-l-cysteine (L-cysNO), and found mesenteric vascular conductance increased (137 ± 3%) significantly more than femoral conductance (26 ± 25%). Similar results were found in wire myography studies of isolated sheep mesenteric and femoral arteries. Vasodilation by SNOs was attenuated in both vessel types by the presence of ODQ (sGC inhibitor), and both YC-1 (sGC agonist) and 8-Br-cGMP (cGMP analog) mediated more potent relaxation in mesenteric arteries than femoral arteries. The vasodilatory difference between mesenteric and femoral arteries was eliminated by antagonists of either protein kinase G or L-type Ca(2+) channels. Western immunoblots showed a larger L-type Ca(2+)/sGC abundance ratio in mesenteric arteries than in femoral arteries. Fetal sheep mesenteric arteries were more responsive to SNOs than adult mesenteric arteries, and had a greater L-Ca(2+)/sGC ratio (p = 0.047 and r = -0.906 for correlation between Emax and L-Ca(2+)/sGC). These results suggest that mesenteric arteries, especially those in fetus, are more responsive to SNO-mediated vasodilation than femoral arteries due to a greater role of the L-type calcium channel in the NO/cGMP pathway. PMID:27235767

  15. 75 FR 21641 - Infusion Pumps; Public Meeting; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... HUMAN SERVICES Food and Drug Administration Infusion Pumps; Public Meeting; Request for Comments AGENCY... Food and Drug Administration (FDA) is announcing a public meeting regarding external infusion pumps... infusion pump use, to help the agency identify quality assurance strategies to mitigate these problems,...

  16. [Portable elastomeric infusion system applied to patients with knee prosthesis].

    PubMed

    Soler, Gemma; Quiles, Olga; Nicolau, Agnes; Faura, Teresa; Moreno, Cristina

    2007-03-01

    An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion. PMID:17474369

  17. Career Education Infused into the Social Studies Curriculum.

    ERIC Educational Resources Information Center

    Hudson, Patricia; Griggs, Shirley A.

    Social studies teachers can help students develop self- and career awareness by infusing career education into the social studies curriculum. The infusion method of career education is preferred since it can make the content of lessons more relevant for students. In addition, infusion of career education is particularly appropriate in social…

  18. 40 CFR 721.10287 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10287 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-11-188) is subject to reporting under this section for...

  19. 40 CFR 721.10706 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10706 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-12-576) is subject to reporting under this section for...

  20. 40 CFR 721.10287 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10287 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-11-188) is subject to reporting under this section for...

  1. 40 CFR 721.10287 - Infused carbon nanostructures (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Infused carbon nanostructures (generic... Specific Chemical Substances § 721.10287 Infused carbon nanostructures (generic). (a) Chemical substance... infused carbon nanostructures (PMN P-11-188) is subject to reporting under this section for...

  2. [The anticancer drug Kang-Lai-Te emulsion for infusion].

    PubMed

    Li Dapeng

    2005-01-01

    Kanglaite (KLT) emulsion for infusion is a new type of anticancer drug, prepared by extracting active antitumor components from the primary product of the Chinese plant Semen Coicis using modern technology, and formed as lipid emulsion for intravenous and intra-arterial injections. Clinical application of this drug demonstrates high efficacy of KLT in treatment of various tumors, such as lung, hepatic, stomach, and breast carcinomas. Its use leads to a significant increase of immune functions and improves life quality: when combined with radio-, chemotherapy, and auxiliary therapy, it leads to a significant increase of the therapeutic effect and reduces the toxic effects of these treatments. Deep study of the mechanism of KLT action, performed in large research centers of China, has demonstrated that the drug blocks tumor cell mitosis at the boundary of G2 and M phases of the cell cycle, induces tumor cell apoptosis, increases the expression of Fas/Apo-1 gene, which inhibits the growth of tumor cells, and reduces the expression of Bel-2 gene, which promotes it, inhibits angiogenesis, actively decreases cancer cachexy, and is able to overcome multiple drug resistance of tumor cells. PMID:16250329

  3. Impact of priming the infusion system on the performance of target-controlled infusion of remifentanil

    PubMed Central

    Kim, Jong-Yeop; Moon, Bong-Ki; Lee, Jong Hyuk; Jo, Youn Yi

    2013-01-01

    Background The start-up behavior of syringe and syringe pump is known to be one of the causes of inaccurate intravenous infusion. This study evaluated the method of priming the infusion system (PRIMING), and its impact on the target-controlled infusion (TCI) of two remifentanil diluents. Methods PRIMING was performed using an evacuation of 2.0 ml to the atmosphere prior to TCI. Forty-eight TCI, using 50 µg/ml (Remi50) or 20 µg/ml (Remi20) of diluents, were performed targeting 4.0 ng/ml of effect-site concentration (Ceff), with PRIMING or not. The gravimetrical measurements of the delivered infusates reproduced actual Ceff. The bolus amount and time to reach 95% target were compared. Results Without PRIMING, Remi50 infused less bolus (43 ± 23 %) than Remi20 (19 ± 9 %) (P = 0.003), and showed more delayed increase of Ceff (11.2 ± 4.0 min) than Remi20 (7.4 ± 0.4 min) (P = 0.028). However, PRIMING significantly decreased the deficit of the bolus (2 ± 1%), as well as the delay of the increase of Ceff in Remi50 (1.2 ± 0.2 min) (both P < 0.001). In addition, with PRIMING, the start-up bolus showed minimal difference to the nominal bolus (1 and 2%), and Ceff were increased to 4.0 ± 0.1 ng/ml at the expected time of peak effect, irrespective of the diluents. Conclusions Proper operation of the syringe pump used in the priming of the syringe may be helpful in reduction of the inaccuracy of TCI, particularly during the early phase of infusion, or the infusion of a more concentrated diluent. PMID:23741562

  4. Software Engineering Technology Infusion Within NASA

    NASA Technical Reports Server (NTRS)

    Zelkowitz, Marvin V.

    1996-01-01

    Abstract technology transfer is of crucial concern to both government and industry today. In this paper, several software engineering technologies used within NASA are studied, and the mechanisms, schedules, and efforts at transferring these technologies are investigated. The goals of this study are: 1) to understand the difference between technology transfer (the adoption of a new method by large segments of an industry) as an industry-wide phenomenon and the adoption of a new technology by an individual organization (called technology infusion); and 2) to see if software engineering technology transfer differs from other engineering disciplines. While there is great interest today in developing technology transfer models for industry, it is the technology infusion process that actually causes changes in the current state of the practice.

  5. Irreversible sediment formation in green tea infusions.

    PubMed

    Xu, Yong-Quan; Chen, Gen-Sheng; Wang, Qiu-Shuang; Yuan, Hai-Bo; Feng, Chun-Hong; Yin, Jun-Feng

    2012-03-01

    The formation of irreversible tea sediment (IRS) and its chemical components in green tea infusions were investigated. The results showed that the amounts of IRS in the green tea infusions from various tea cultivars ranged from 0.10 to 1.47 mg/mL. The amount of IRS was influenced remarkably by the chemical components in the green tea infusion. Principal component analysis and regression analysis indicated that gallated catechins, Mn, Ca, caffeine, Na, and (-)-gallocatechin gallate (GCG) were the principal components. IRS (mg/mL) = -4.226 + 0.275 gallated catechins + 79.551 Na + 7.321 Mn + 21.055 Ca + 0.513 caffeine - 0.129 GCG (R2 = 0.697). The contents of the main chemical components in the reversible tea sediment (RTS) and IRS were markedly different, especially the minerals. Large amount of minerals participated in the formation of irreversible green tea sediment. The amount of IRS increased with the extraction temperature. PMID:22329921

  6. QSAR study of substituted 2-pyridinyl guanidines as selective urokinase-type plasminogen activator (uPA) inhibitors.

    PubMed

    Karthikeyan, C; Moorthy, N S Hari Narayana; Trivedi, Piyush

    2009-02-01

    A quantitative structure-activity relationship analysis was conducted on two different series of pyridinylguanidines acting as inhibitors of urokinase-type plasminogen activator using QuaSAR descriptors of molecular modeling software MOE. Multiple linear regression analysis following a stepwise scheme was employed to generate QSARs that relate molecular descriptors to uPA inhibitory activity data of the title compounds. Among the several QSARs generated by MLR analysis, the best models were selected on the basis of their statistical significance and predictive potential. The interpretation of the selected QSAR models suggest that uPA inhibitory activity of compounds in series 1 is influenced by their molecular shape, molecular flexibility and halogen atoms in the molecule whereas the uPA inhibitory potency of compounds in series 2 is dependent on molecular lipophilicity, number of double bonds and spatial orientation of bulky substituents in the molecule. PMID:19012070

  7. Defect of vacuolar protein sorting stimulates proteolytic processing of human urokinase-type plasminogen activator in the yeast Hansenula polymorpha.

    PubMed

    Agaphonov, Michael; Romanova, Nina; Sokolov, Sviatoslav; Iline, Anna; Kalebina, Tatyana; Gellissen, Gerd; Ter-Avanesyan, Michael

    2005-11-01

    Human urokinase-type plasminogen activator (uPA) is poorly secreted by yeast cells. Here, we have selected Hansenula polymorpha mutants with increased productivity of active extracellular uPA. Several of the obtained mutants also demonstrated a defect of sorting of carboxypeptidase Y to the vacuole and the mutant loci have been identified in six of them. All these mutations damaged genes involved in protein traffic between the Golgi apparatus and the vacuole, namely PEP3, VPS8, VPS10, VPS17, and VPS35. We have shown that inactivation of the VPS10 gene encoding the vacuolar protein sorting receptor does not increase uPA secretion but stimulates its proteolytic processing. PMID:16181812

  8. Re-engineering the Immune Response to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor.

    PubMed

    Rullo, Anthony F; Fitzgerald, Kelly J; Muthusamy, Viswanathan; Liu, Min; Yuan, Cai; Huang, Mingdong; Kim, Minsup; Cho, Art E; Spiegel, David A

    2016-03-01

    Developing selective strategies to treat metastatic cancers remains a significant challenge. Herein, we report the first antibody-recruiting small molecule (ARM) that is capable of recognizing the urokinase-type plasminogen activator receptor (uPAR), a uniquely overexpressed cancer cell-surface marker, and facilitating the immune-mediated destruction of cancer cells. A co-crystal structure of the ARM-U2/uPAR complex was obtained, representing the first crystal structure of uPAR complexed with a non-peptide ligand. Finally, we demonstrated that ARM-U2 substantially suppresses tumor growth in vivo with no evidence of weight loss, unlike the standard-of-care agent doxorubicin. This work underscores the promise of antibody-recruiting molecules as immunotherapeutics for treating cancer. PMID:26879524

  9. Pharmacokinetics of sufentanil during long-term infusion in critically ill pediatric patients.

    PubMed

    Bartkowska-Śniatkowska, Alicja; Bienert, Agnieszka; Wiczling, Paweł; Rosada-Kurasińska, Jowita; Zielińska, Marzena; Warzybok, Justyna; Borsuk, Agnieszka; Tibboel, Dick; Kaliszan, Roman; Grześkowiak, Edmund

    2016-01-01

    The aim of this study was to develop a population pharmacokinetic model of sufentanil and to assess the influence of covariates in critically ill children admitted to a pediatric intensive care unit. After institutional approval, 41 children were enrolled in the study. Blood samples for pharmacokinetic (PK) assessment were collected from routinely placed arterial catheters during and after discontinuation of infusion. Population nonlinear mixed-effects modeling was performed using NONMEM. A 2-compartment model described sufentanil PK sufficiently. Typical values of the central and peripheral volume of distribution and the metabolic and intercompartmental clearance for a theoretical patient weighing 70 kg were VC = 7.90 l, VT  = 481 L, Cl =  5.3 L/h, and Q = 38.3 L/h, respectively. High interindividual variability of all PK parameters was noted. Allometric/isometric principles to scale sufentanil PK revealed that to achieve the same steady-state sufentanil concentrations in plasma for pediatric patients of different body weights, the infusion rate should follow the formula (infusion rate for a 70-kg adult patient, μg/h) × (body weight/70 kg)(0.75). Severity of illness described by PRISM score, the monitored physiological and laboratory parameters, and coadministered drugs such as vasopressors were not found to be significant covariates. PMID:26105145

  10. Atrial natriuretic peptide infusion in chronic heart failure in the rat.

    PubMed

    Kohzuki, M; Hodsman, G P; Harrison, R W; Western, P S; Johnston, C I

    1989-01-01

    The natriuretic, diuretic, and hypotensive responses to infused atrial natriuretic peptide (ANP) were measured in rats 4 weeks after myocardial infarction induced by coronary artery ligation. Rat [1-28]-ANP was infused intravenously in doses of 0.1, 0.3, and 1.0 microgram/kg/min for 30 min each under pentobarbital anesthesia. There was a marked natriuresis, diuresis, and fall in blood pressure in rats with infarction but each response was significantly attenuated when compared with sham-operated controls (ANOVA: p less than 0.01, p less than 0.05, and p less than 0.01, respectively). Urinary cyclic guanosine monophosphate (cGMP) excretion in rats with infarction was higher than that of controls but rose to the same absolute level in both groups in response to ANP infusion (0.3 microgram/kg/min). Reduced ANP responsiveness may result from impaired postreceptor mechanisms or from physiological antagonism by angiotensin II. Reduced ANP responsiveness may partly explain impaired salt handling in heart failure. PMID:2473348

  11. Atrial natriuretic peptide increases microvascular blood flow and macromolecular escape during renin infusion in the hamster

    SciTech Connect

    Boric, M.P.; Albertini, R. )

    1990-02-01

    The effects of Atrial Natriuretic Peptide (ANP) on microvascular hemodynamics and macromolecular permselectivity were studied in the hamster cheek pouch under resting conditions and during intravenous renin infusion. Fluorescent intravital microscopy was used to observe arteriolar diameters and to detect escape of fluorescent dextran of 150 K-Daltons (FITC-Dx-150). Microvascular plasma flow was estimated by clearance of 51Cr-EDTA and net macromolecular transport by clearance of FITC-Dx-150. At rest, topical ANP (2-250 ng/ml) had no effect on arteriolar diameter, 51Cr-EDTA clearance, relative vascular conductance (RVC) or FITC-Dx-150 clearance. Infusion of renin (10 mU/Kg/Hr, iv) elevated systemic arterial pressure by 30% and reduced cheek pouch RVC by 26%. During renin infusion, topical ANP (50 ng/ml) produced transient arteriolar vasodilation, and increased 51Cr-EDTA clearance (+35%), RVC (+58%) and FITC-Dx-150 clearance (+54%), without affecting systemic pressure. ANP did not induce venular leakage sites under any condition, but changes in FITC-Dx-150 clearance were highly correlated with changes in 51Cr-EDTA clearance, suggesting that the larger macromolecular escape was due to increases in microvascular blood flow and capillary/post-capillary hydrostatic pressure.

  12. Nonstationary disposition of valproic acid during prolonged intravenous infusion: contributions of unbound clearance and protein binding.

    PubMed

    Arens, T L; Pollack, G M

    2001-09-01

    Circadian variations in disposition have been observed for a variety of agents, including anticonvulsants. Valproic acid (VPA), an anticonvulsant used to control generalized and partial seizures, has exhibited diurnal oscillations in steady-state concentrations during long-term administration to humans and non-human primates. The present study was conducted to assess potential diurnal changes in the disposition of VPA during prolonged i.v. infusion in rats. Animals, maintained on a strict 12-h per day light cycle, were equipped with venous cannulae and an arterial microdialysis probe. VPA was administered as a 50-mg/kg loading dose followed by a 42 mg/kg/h infusion for 70 h. Blood and microdialysate samples were obtained at timed intervals after establishment of steady-state throughout two complete light/dark cycles; and total (serum) and unbound (microdialysate) VPA was determined by gas chromatography. Modest oscillations (6-7 h period) in total and unbound VPA were observed; clearance and binding parameters were not different between light and dark periods. However, unbound clearance increased, and unbound fraction decreased, with time over the course of the infusion. These results suggest that time-dependent changes in VPA disposition occur in rats, although oscillations in steady-state concentrations do not appear to be diurnal in nature. PMID:11754040

  13. Total i.v. anaesthesia with propofol and alfentanil for coronary artery bypass grafting.

    PubMed

    Manara, A R; Monk, C R; Bolsin, S N; Prys-Roberts, C

    1991-06-01

    The haemodynamic effects of total i.v. anaesthesia with a combination of propofol and alfentanil infusions were studied in eight patients with good left ventricular function undergoing coronary artery bypass surgery. Haemodynamic indices were measured before anaesthesia and at specified intervals before cardiopulmonary bypass. The technique resulted in haemodynamic changes comparable to those reported with opioid-based anaesthesia for coronary artery surgery, and has potential advantages. PMID:2064887

  14. Hemodynamic effects of 6% hydroxyethyl starch infusion in sevoflurane-anesthetized thoroughbred horses.

    PubMed

    Ohta, Minoru; Kurimoto, Shinjiro; Tokushige, Hirotaka; Kuroda, Taisuke; Ishikawa, Yuhiro

    2013-07-31

    To determine hemodynamic effects of hydroxyethyl starch (HES) infusion during anesthesia in horses, incremental doses of 6% HES were administered to 6 healthy Thoroughbred horses. Anesthesia was induced with xylazine, guaifenesin and thiopental and maintained with sevoflurane at 2.8% of end-tidal concentration in all horses. The horses were positioned in right lateral recumbency and administered 3 intravenous dose of 6% HES (5 ml/kg) over 15 min with 15-min intervals in addition to constant infusion of lactated Ringer's solution at 10 ml/kg/hr. Hemodynamic parameters were measured before and every 15 min until 90 min after the administration of 6% HES. There was no significant change in heart rate and arterial blood pressures throughout the experiment. The HES administration produced significant increases in mean right atrial pressure, stroke volume, cardiac output (CO) and decrease in systemic vascular resistance (SVR) in a dose-dependent manner. There was no significant change in electrolytes (Na(+), K(+), Cl(-)) throughout the experiment, however, packed cell volume, hemoglobin concentration, and total protein and albumin concentrations decreased in a dose-dependent manner following the HES administration. In conclusion, the HES administration provides a dose-dependent increase in CO, but has no impact upon arterial blood pressures due to a simultaneous decrease in SVR. PMID:23411483

  15. Cardiopulmonary Effects of Constant-Rate Infusion of Lidocaine for Anesthesia during Abdominal Surgery in Goats.

    PubMed

    Malavasi, Lais M; Greene, Stephen A; Gay, John M; Grubb, Tammy L

    2016-01-01

    Lidocaine is commonly used in ruminants but has an anecdotal history of being toxic to goats. To evaluate lidocaine's effects on selected cardiopulmonary parameters. Isoflurane-anesthetized adult goats (n = 24) undergoing abdominal surgery received a loading dose of lidocaine (2.5 mg/kg) over 20 min followed by constant-rate infusion of lidocaine (100 μg/kg/min); control animals received saline instead of lidocaine. Data collected at predetermined time points during the 60-min surgery included heart rate, mean arterial blood pressure, pO2, and pCO2. According to Welch 2-sample t tests, cardiopulmonary variables did not differ between groups. For example, after administration of the loading dose, goats in the lidocaine group had a mean heart rate of 88 ± 28 bpm, mean arterial blood pressure of 70 ± 19 mm Hg, pCO2 of 65 ± 13 mm Hg, and pO2 of 212 ± 99 mm Hg; in the saline group, these values were 90 ± 16 bpm, 76 ± 12 mm Hg, 61 ± 9 mm Hg, and 209 ± 83 mm Hg, respectively. One goat in the saline group required an additional dose of butorphanol. Overall our findings indicate that, at the dose provided, intravenous lidocaine did not cause adverse cardiopulmonary effects in adult goats undergoing abdominal surgery. Adding lidocaine infusion during general anesthesia is an option for enhancing transoperative analgesia in goats. PMID:27423150

  16. Accuracy of different oxygenation indices in estimating intrapulmonary shunting at increasing infusion rates of dobutamine in horses under general anaesthesia.

    PubMed

    Briganti, A; Portela, D A; Grasso, S; Sgorbini, M; Tayari, H; Bassini, J R Fusar; Vitale, V; Romano, M S; Crovace, A; Breghi, G; Staffieri, F

    2015-06-01

    The aim of this study was to evaluate the correlation of commonly used oxygenation indices with venous admixture (Qs/Qt) in anaesthetised horses under different infusion rates of dobutamine. Six female horses were anaesthetised with acepromazine, xylazine, diazepam, ketamine, and isoflurane, and then intubated and mechanically ventilated with 100% O2. A Swan-Ganz catheter was introduced into the left jugular vein and its tip advanced into the pulmonary artery. Horses received different standardised rates of dobutamine. For each horse, eight samples of arterial and mixed venous blood were simultaneously obtained at fixed times. Arterial and venous haemoglobin (Hb) concentration and O2 saturation, arterial oxygen partial pressure (PaO2), venous oxygen partial pressure (PvO2), and barometric pressure were measured. Arterial (CaO2), mixed venous (CvO2), and capillary (Cc'O2) oxygen contents were calculated using standard formulae. The correlations between F-shunt, arterial oxygen tension to fraction of inspired oxygen ratio (PaO2/FiO2), arterial to alveolar oxygen tension ratio (PaO2/PAO2), alveolar to arterial oxygen tension difference (P[A - a]O2), and respiratory index (P[A - a]O2/PaO2) were tested with linear regression analysis. The goodness-of-fit for each calculated formula was evaluated by means of the coefficient of determination (r(2)). The agreement between Qs/Qt and F-shunt was analysed with the Bland-Altman test. All tested oxygen tension-based indices were weakly correlated (r(2) < 0.2) with the Qs/Qt, whereas F-shunt showed a stronger correlation (r(2) = 0.73). F-shunt also showed substantial agreement with Qs/Qt independent of the dobutamine infusion rate. F-shunt better correlated with Qs/Qt than other oxygen indices in isoflurane-anaesthetised horses under different infusion rates of dobutamine. PMID:25920771

  17. Carotid artery anatomy (image)

    MedlinePlus

    There are four carotid arteries, two on each side of the neck: right and left internal carotid arteries, and right and left external carotid arteries. The carotid arteries deliver oxygen-rich blood from the heart to the head and brain.

  18. Impact of local endothelial challenge with cytomegalovirus or glycoprotein B on vasodilation in intact pressurized arteries from nonpregnant and pregnant mice.

    PubMed

    Gombos, Randi B; Teefy, Jana; Lee, Albert; Hemmings, Denise G

    2012-10-01

    Cytomegalovirus (CMV) infections are associated with vascular diseases in the human population. We have previously shown vascular dysfunction in systemic and uterine arteries dissected from nonpregnant (NP) mouse CMV (mCMV)-infected mice that was further impaired during late pregnancy (LP). CMV attachment alone through glycoprotein B (GB) can generate signals that impact vascular tone regulation. However, the contribution of direct virus interactions with endothelium to the vascular dysfunction we previously observed after in vivo mCMV infection is not known. We used a pressure myograph system to infuse GB or whole intact mCMV inside arteries dissected from uninfected mice and assessed vasodilation to methacholine infused inside pressurized arteries rather than applied abluminally. These results were compared to those observed after methacholine infusion into untreated arteries dissected from mCMV-infected mice. In mesenteric arteries, vasodilation to infused methacholine did not differ among treatments in NP or LP groups in contrast to previously published studies. However, increased vasoconstrictor activity was unmasked after blocking thromboxane receptors or prostaglandin production. Vasodilation in uterine arteries from uninfected NP mice to infused methacholine was increased by both GB and whole intact mCMV pretreatment. Untreated uterine arteries from mCMV-infected NP mice showed even greater vasodilation. There was no effect of GB or whole intact mCMV pretreatment in uterine arteries from uninfected LP mice, whereas vasodilation to infused methacholine was reduced in untreated uterine arteries from mCMV-infected LP mice. CMV exerts direct effects on vascular function which should be considered during viral reactivation leading to viremia and during GB-based vaccine administration. PMID:22875909

  19. Vapor resistant arteries

    NASA Technical Reports Server (NTRS)

    Shaubach, Robert M. (Inventor); Dussinger, Peter M. (Inventor); Buchko, Matthew T. (Inventor)

    1989-01-01

    A vapor block resistant liquid artery structure for heat pipes. A solid tube artery with openings is encased in the sintered material of a heat pipe wick. The openings are limited to that side of the artery which is most remote from the heat source. The liquid in the artery can thus exit the artery through the openings and wet the sintered sheath, but vapor generated at the heat source is unlikely to move around the solid wall of the artery and reverse its direction in order to penetrate the artery through the openings. An alternate embodiment uses finer pore size wick material to resist vapor entry.

  20. Enhanced Extracorporeal CO2 Removal by Regional Blood Acidification: Effect of Infusion of Three Metabolizable Acids.

    PubMed

    Scaravilli, Vittorio; Kreyer, Stefan; Linden, Katharina; Belenkiy, Slava; Pesenti, Antonio; Zanella, Alberto; Cancio, Leopoldo C; Batchinsky, Andriy I

    2015-01-01

    Acidification of blood entering a membrane lung (ML) with lactic acid enhances CO2 removal (VCO2ML). We compared the effects of infusion of acetic, citric, and lactic acids on VCO2ML. Three sheep were connected to a custom-made circuit, consisting of a Hemolung device (Alung Technologies, Pittsburgh, PA), a hemofilter (NxStage, NxStage Medical, Lawrence, MA), and a peristaltic pump recirculating ultrafiltrate before the ML. Blood flow was set at 250 ml/min, gas flow (GF) at 10 L/min, and recirculating ultrafiltrate flow at 100 ml/min. Acetic (4.4 M), citric (0.4 M), or lactic (4.4 M) acids were infused in the ultrafiltrate at 1.5 mEq/min, for 2 hours each, in randomized fashion. VCO2ML was measured by the Hemolung built-in capnometer. Circuit and arterial blood gas samples were collected at baseline and during acid infusion. Hemodynamics and ventilation were monitored. Acetic, citric, or lactic acids similarly enhanced VCO2ML (+35%), from 37.4 ± 3.6 to 50.6 ± 7.4, 49.8 ± 5.6, and 52.0 ± 8.2 ml/min, respectively. Acids similarly decreased pH, increased pCO2, and reduced HCO3 of the post-acid extracorporeal blood sample. No significant effects on arterial gas values, ventilation, or hemodynamics were observed. In conclusion, it is possible to increase VCO2ML by more than one-third using any one of the three metabolizable acids. PMID:26273934

  1. In vivo laser assisted end-to-end anastomosis with ICG-infused chitosan patches

    NASA Astrophysics Data System (ADS)

    Rossi, Francesca; Matteini, Paolo; Esposito, Giuseppe; Scerrati, Alba; Albanese, Alessio; Puca, Alfredo; Maira, Giulio; Rossi, Giacomo; Pini, Roberto

    2011-07-01

    Laser assisted vascular repair is a new optimized technique based on the use of ICG-infused chitosan patch to close a vessel wound, with or even without few supporting single stitches. We present an in vivo experimental study on an innovative end-to-end laser assisted vascular anastomotic (LAVA) technique, performed with the application of ICGinfused chitosan patches. The photostability and the mechanical properties of ICG-infused chitosan films were preliminary measured. The in vivo study was performed in 10 New Zealand rabbits. After anesthesia, a 3-cm segment of the right common carotid artery was exposed, thus clamped proximally and distally. The artery was then interrupted by means of a full thickness cut. Three single microsutures were used to approximate the two vessel edges. The ICG-infused chitosan patch was rolled all over the anastomotic site and welded by the use of a diode laser emitting at 810 nm and equipped with a 300 μm diameter optical fiber. Welding was obtained by delivering single laser spots to induce local patch/tissue adhesion. The result was an immediate closure of the anastomosis, with no bleeding at clamps release. Thus animals underwent different follow-up periods, in order to evaluate the welded vessels over time. At follow-up examinations, all the anastomoses were patent and no bleeding signs were documented. Samples of welded vessels underwent histological examinations. Results showed that this technique offer several advantages over conventional suturing methods: simplification of the surgical procedure, shortening of the operative time, better re-endothelization and optimal vascular healing process.

  2. Management of Severe Hyponatremia: Infusion of Hypertonic Saline and Desmopressin or Infusion of Vasopressin Inhibitors?

    PubMed Central

    Tzamaloukas, Antonios H.; Shapiro, Joseph I.; Raj, Dominic S.; Murata, Glen H.; Glew, Robert H.

    2014-01-01

    Abstract: Rapid correction of severe hyponatremia carries the risk of osmotic demyelination. Two recently introduced methods of correction of hyponatremia have diametrically opposite effects on aquaresis. Inhibitors of vasopressin V2 receptor (vaptans) lead to the production of dilute urine, whereas infusion of desmopressin causes urinary concentration. Identification of the category of hyponatremia that will benefit from one or the other treatment is critical. In general, vaptans are effective in hyponatremias presenting with concentrated urine and, with the exception of hypovolemic hyponatremia, can be used as their primary treatment. Desmopressin is effective in hyponatremias presenting with dilute urine or developing urinary dilution after saline infusion. In this setting, desmopressin infusion helps prevent overcorrection of the hyponatremia. Monitoring of the changes in serum sodium concentration as a guide to treatment changes is imperative regardless of the initial treatment of severe hyponatremia. PMID:25247759

  3. Immediate infusion-related adverse reactions to intravenous immunoglobulin in a prospective cohort of 1765 infusions.

    PubMed

    Bichuetti-Silva, Danielli C; Furlan, Fernanda P; Nobre, Fernanda A; Pereira, Camila T M; Gonçalves, Tessa R T; Gouveia-Pereira, Mariana; Rota, Rafael; Tavares, Lusinete; Mazzucchelli, Juliana T L; Costa-Carvalho, Beatriz T

    2014-12-01

    Intravenous immunoglobulin (IVIG) is increasingly recommended for many diseases apart from primary immunodeficiency diseases (PID). Although effective and safe, adverse reactions may occur. We conducted a 2-year prospective observational study in 117 patients with PID who received regular IVIG replacement therapy at a median dose of 600 mg/kg every 3 to 4 weeks to examine IVIG's adverse effects; 1765 infusions were performed (mean=15/patient) in 75 males and 42 females (aged 3 months to 77 years) in 3 groups: ≤ 9 years (34.2%), 10-19 years (26.5%), and ≥ 20 years (39.3%). Fifty patients had common variable immunodeficiency (CVID), 11 had X-linked agammaglobulinemia (XLA), and 55 had other immune system disorders. The drugs administered were Octagam® (49.1%), Tegeline® (17.3%), Imunoglobulin® (18.6%), Flebogama® (12.9%), Vigam® (1.2%), and Kiovig® (0.4%). Immediate infusion-related adverse reactions occurred in the cases of 38 out 1765 infusions (2.15%, IC95% 1.53%-2.94%), which were classified as mild (81.6%), moderate (10.5%), or severe (7.9%). Time until reaction ranged from 10 to 240 min (mean = 85.7, median = 60). Reaction rates were similar across age groups. The most common reactions were malaise, headache, and abdominal pain. Reported severe events were tightness of the throat and seizure. All symptoms improved with temporary or complete IVIG interruption and symptomatic medications. Sixteen of 38 reactions to infusions occurred in the presence of an acute infection (p=0.09). Tegeline® represented a greater reaction risk factor than Octagam® (p < 0.001). These results indicate that IVIG infusion can be considered a safe procedure. Low reaction incidence and few severe immediate infusion-related adverse reactions were observed. PMID:25257732

  4. Kiovig for primary immunodeficiency: reduced infusion and decreased costs per infusion.

    PubMed

    Connolly, Mark; Simoens, Steven

    2011-09-01

    Kiovig is a ready-to-use 10% liquid immunoglobulin preparation that is medically indicated for the treatment of primary immunodeficiency. This study aims to conduct an economic evaluation which compares the intravenous immunoglobulin (IVIg) preparations Kiovig, Multigam, and Sandoglobulin from the Belgian societal perspective. As three prospective studies have observed no difference in outcomes, a cost-minimization analysis is considered appropriate to evaluate differences in treatment costs that can arise from IVIgs. A decision-analytic model simulated treatment costs attributed to one infusion. Resource use data were derived from a Dutch costing study. Cost items included immunoglobulin costs, pharmacy administration and nursing costs, mini-forfait for hospital infusion, costs of adverse events, and lost productivity with 2009 as base year. Cost data were identified from published sources and Belgian hospital administrators. A probabilistic sensitivity analysis explored the impact of parameter uncertainty on cost results. Costs per infusion cycle in adult primary immunodeficiency patients were €1,046 (95% confidence interval: €1,006-1,093) with Kiovig; €1,102 (€1,064-1,147) with Multigam; and €1,147 (€1,108-1,193) with Sandoglobulin. The average cost savings per infusion with Kiovig as compared to Multigam and Sandoglobulin amounted to €56 and €101 per infusion. In conclusion, treatment costs with Kiovig were shown to be lower as compared to other IVIgs in Belgium. Reduced costs per infusion were attributed to lower costs associated with treating adverse events and the opportunity cost of nursing time and time off work for working adults. PMID:21570491

  5. Gastric damage following local intra-arterial administration of reactive oxygen metabolites in the rat.

    PubMed Central

    Esplugues, J. V.; Whittle, B. J.

    1989-01-01

    1. The effects of reactive oxygen metabolites on the rat gastric mucosa following close-arterial infusion into the left gastric artery have been determined by macroscopic and histological assessment. 2. Local intra-arterial infusion of hydrogen peroxide (0.6-1.3 mumol kg-1 min-1) induced mucosal injury, characterised by areas of pronounced disruption and haemorrhage, which was prevented by concurrent intravenous administration of catalase. 3. Local infusion of the superoxide generating system xanthine-oxidase and hypoxanthine likewise induced extensive haemorrhagic damage and necrosis of the mucosa. Prolonged incubation of this mixture (10 min) before administration, significantly reduced the degree of injury, indicating the lability of the products so formed. 4. The gastric mucosal injury induced by the superoxide generating system was inhibited by concurrent local infusion of superoxide dismutase (96 u kg-1 min-1), as was the associated increase in mucosal permeability to radiolabelled albumin. 5. Administration of catalase did not inhibit the gastric mucosal damage induced by infusion of xanthine oxidase-hypoxanthine, yet augmented the protective effects of a low dose of superoxide dismutase (46 u kg-1 min-1 i.a.). 6. These findings directly confirm that reactive oxygen metabolites can induce extensive gastric mucosal injury, supporting their role in the pathogenesis of gastric damage following ischaemia and hypotensive shock. Images Figure 2 PMID:2551438

  6. Analysis of plasma serotonin levels and hemodynamic responses following chronic serotonin infusion in broilers challenged with bacterial lipopolysaccharide and microparticles.

    PubMed

    Chapman, M E; Taylor, R L; Wideman, R F

    2008-01-01

    There has been extensive interest in the role of serotonin (5-hydoxytryptamine, 5-HT) in the pathogenesis of pulmonary hypertension because episodes of pulmonary arterial hypertension in humans have been linked to serotoninergic appetite-suppressant drugs. In this study, we investigated the role of serotonin in the development of pulmonary hypertension induced by intravenously injecting bacterial lipopolysaccharide (LPS, endotoxin) and cellulose microparticles. In experiment 1, we used a 5-HT ELISA kit for the in vitro quantitative determination of 5-HT in plasma during the development of pulmonary hypertension induced by injecting LPS and cellulose microparticles i.v. in broilers. In experiment 2, broilers were either chronically infused with 5-HT via surgically implanted osmotic pumps or received sham surgery as a control. After a period of 10 d, the pulmonary arterial pressure was recorded during challenge with injected LPS or microparticles. Microparticles elicited 5-HT plasma levels more than 2-fold greater than those elicited by LPS from 15 to 45 min postinjection. This indicates that 5-HT is an important mediator in the pulmonary hypertensive response of broilers to microparticles, but may not play a prominent role in the pulmonary hypertensive response to LPS. Furthermore, chronic 5-HT infusion via osmotic pumps caused an increase in the duration of the pulmonary hypertensive response of broilers to microparticles, indicating that the infused 5-HT was sequestered by circulating thrombocytes and then released upon microparticle-mediated thrombocyte activation. Serotonin appears to play a less prominent role in the pulmonary hypertensive response of broilers to LPS, indicating that other mediators within the innate response to inflammatory stimuli may also be involved. These results are consistent with our hypothesis that pulmonary arterial hypertension ensues when vasoconstrictors such as 5-HT overwhelm the dilatory affects of vasodilators such as nitric

  7. Hemodynamic and clinical response to three-day infusion of sulmazol (AR-L 115 BS) in severe congestive heart failure.

    PubMed

    Renard, M; Jacobs, P; Dechamps, P; Dresse, A; Bernard, R

    1983-10-01

    Sulmazol (AR-L 115 BS) is a new positively inotropic drug with arterial and venous vasodilating properties. We studied the effects of sulmazol (three-day infusion) on clinical tolerance, hemodynamics, and blood gas levels in ten patients with severe chronic heart failure. The hemodynamic monitoring included a Swan-Ganz catheter in the pulmonary artery and a radial catheter. Blood gas levels were determined on samples of arterial and mixed venous blood. After 24 hours of infusion, there was a significant increase in cardiac index (2 to 2.5 L/min/sq m; p less than 0.005) and a significant decrease in pulmonary wedge pressure (28 to 19 mm Hg; p less than 0.001) and in right atrial pressure (7 to 4 mm Hg; p less than 0.001) without significant changes in heart rate and systolic blood pressure. These beneficial effects lasted during the three days of infusion. Oxygen delivery was significantly increased (350 to 443 ml/min/sq m; p less than 0.005) without significant change in arterial oxygen tension. The side effects included nausea, vomiting, anorexia, and mild thrombocytopenia. We conclude that sulmazol is a potent drug which may improve severely deteriorated left and right ventricular function in patients with chronic refractory heart failure without affecting the heart rate and the systolic blood pressure. PMID:6413136

  8. Initial Observations of the Effects of Calcium Chloride Infusions in Pediatric Patients with Low Cardiac Output.

    PubMed

    Averin, Konstantin; Villa, Chet; Krawczeski, Catherine D; Pratt, Jesse; King, Eileen; Jefferies, John L; Nelson, David P; Cooper, David S; Ryan, Thomas D; Sawyer, Jaclyn; Towbin, Jeffrey A; Lorts, Angela

    2016-03-01

    Myocardial contractility and relaxation are highly dependent on calcium homeostasis. Immature myocardium, as in pediatric patients, is thought to be more dependent on extracellular calcium for optimal function. For this reason, intravenous calcium chloride infusions may improve myocardial function in the pediatric patient. The objectives of this study were to report the hemodynamic changes seen after administration of continuous calcium chloride to critically ill children. We retrospectively identified pediatric patients (newborn to 17 years old) with hemodynamic instability admitted to the cardiac ICU between May 2011 and May 2012 who received a continuous infusion of calcium chloride. The primary outcome was improvement in cardiac output, assessed by arterial-mixed venous oxygen saturation (A-V) difference. Sixty-eight patients, mean age 0.87 ± 2.67 years, received a total of 116 calcium infusions. Calcium chloride infusions resulted in significant improvements in primary and secondary measures of cardiac output at 2 and 6 h. Six hours after calcium initiation, A-V oxygen saturation difference decreased by 7.4 % (32.6 ± 2.1 to 25.2 ± 2.0 %, p < 0.001), rSO2 increased by 5.5 % (63.1 vs 68.6 %, p < 0.001), and serum lactate decreased by 0.9 mmol/l (3.3 vs 2.4 mmol/l, p < 0.001) with no change in HR (149.1 vs 145.6 bpm p = 0.07). Urine output increased 0.66 ml/kg/h in the 8-h period after calcium initiation when compared to pre-initiation (p = 0.003). Neonates had the strongest evidence of effectiveness with other age groups trending toward significance. Calcium chloride infusions improve markers of cardiac output in a heterogenous group of pediatric patients in a cardiac ICU. Neonates appear to derive the most benefit from utilization of these infusions. PMID:26687150

  9. Effect of peri-operative intravenous infusion of lignocaine on haemodynamic responses to intubation, extubation and post-operative analgesia

    PubMed Central

    Jain, Shruti; Khan, Rashid M

    2015-01-01

    Background and Aims: Lignocaine in intravenous (IV) bolus dose has been used for minimising haemodynamic changes associated with intubation and extubation. Furthermore, IV infusion has been used for post-operative analgesia. We investigated whether IV peri-operative lignocaine (bolus and infusion) would be able to produce both the effects simultaneously in elective laparoscopic cholecystectomies. Methods: In this randomised prospective study, 60 patients undergoing elective laparoscopic cholecystectomy were randomly divided into two groups of 30 each. In Group A, patients received 6 ml normal saline as bolus over 10 min followed by 6 ml/h infusion whereas in Group B, patients received preservative free 2% lignocaine 1.5 mg/kg IV bolus (made to a volume of 6 ml with normal saline) administered over a period of 10 min and thereafter an infusion at a rate of 1.5 mg/kg/h (pre-diluted in normal saline made to a volume of 6 ml/h. P < 0.05 was considered as significant. Results: The rise in pulse rate (PR) and mean arterial pressure (MAP) were less in Group B as compared to the Group A (P < 0.05) during intubation as well as during extubation. Furthermore, the Group B had significant longer mean pain-free post-operative period of 5½ h as compared to 54.43 min in the Group A (P < 0.05). Conclusion: Administration of lignocaine infusion attenuates the rise in PR as well as MAP during the peri-intubation and peri-extubation period. Furthermore, infusion of lignocaine significantly increases the mean pain-free period post-operatively. PMID:26195829

  10. Endothelial Cell Toxicity of Vancomycin Infusion Combined with Other Antibiotics

    PubMed Central

    Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

    2015-01-01

    French guidelines recommend central intravenous (i.v.) infusion for high concentrations of vancomycin, but peripheral intravenous (p.i.v.) infusion is often preferred in intensive care units. Vancomycin infusion has been implicated in cases of phlebitis, with endothelial toxicity depending on the drug concentration and the duration of the infusion. Vancomycin is frequently infused in combination with other i.v. antibiotics through the same administrative Y site, but the local toxicity of such combinations has been poorly evaluated. Such an assessment could improve vancomycin infusion procedures in hospitals. Human umbilical vein endothelial cells (HUVEC) were challenged with clinical doses of vancomycin over 24 h with or without other i.v. antibiotics. Cell death was measured with the alamarBlue test. We observed an excess cellular death rate without any synergistic effect but dependent on the numbers of combined infusions when vancomycin and erythromycin or gentamicin were infused through the same Y site. Incompatibility between vancomycin and piperacillin-tazobactam was not observed in our study, and rinsing the cells between the two antibiotic infusions did not reduce endothelial toxicity. No endothelial toxicity of imipenem-cilastatin was observed when combined with vancomycin. p.i.v. vancomycin infusion in combination with other medications requires new recommendations to prevent phlebitis, including limiting coinfusion on the same line, reducing the infusion rate, and choosing an intermittent infusion method. Further studies need to be carried out to explore other drug combinations in long-term vancomycin p.i.v. therapy so as to gain insight into the mechanisms of drug incompatibility under multidrug infusion conditions. PMID:26055373

  11. Effects of vascular infusion with a solution of saccharides, sodium chloride, and phosphates with or without vitamin C on carcass traits, Warner-Bratzler shear force, flavor-profile, and descriptive-attribute characteristics of steaks and ground beef from Charolais cattle.

    PubMed

    Yancey, E J; Dikeman, M E; Addis, P B; Katsanidis, E; Pullen, M

    2002-04-01

    Two groups of 18 grain-finished steers were utilized. Nine from one group were infused via the carotid artery immediately after jugular vein exsanguination with an aqueous solution containing saccharides, NaCl, and phosphates (MPSC; MPSC, Inc., Eden Prairie, MN, USA). Nine steers served as non-infused controls (CON). An additional 18 steers were infused with either MPSC (n=9) or MPSC plus 1000 ppm vitamin C (MPSC+C, n=9) solutions. Steers infused with MPSC had higher dressing percentages and organ weights than CON steers. Vascular infusion with MPSC had no effects on USDA yield or quality grade traits, descriptive-attribute sensory panel evaluations, or Warner-Bratzler shear force of longissimus lumborum and semitendinosus muscles. Vascular infusion with MPSC resulted in some significant, but inconsistent effects on flavor-profile characteristics of cooked beef. The addition of vitamin C to the MPSC solution did not provide any benefit. PMID:22063636

  12. Coronary artery occlusion extends perfusion territory boundaries through microvascular collaterals.

    PubMed

    Cicutti, N; Rakusan, K; Downey, H F

    1994-01-01

    Simultaneous in vivo infusions of two different colored 10 microns microsphere suspensions into the left anterior descending (LAD; red spheres) and left circumflex (LCx; blue spheres) coronary arteries of nine anesthetized dogs identified a specific region of canine myocardium perfused by both arterial branches. Subsequently, the LAD was ligated and a third (green) set of micropheres was infused into the patent LCx artery. Analysis of 40 microns serial sections of tissue revealed interface zones with capillaries perfused by both arteries. The first zone, defined as the Interface Transistion Zone (ITZ) was formed by an intermingling of microvessels supplied by the parent arteries of the adjacent perfusion territories; it separated tissue containing only one or the other colored microspheres. Another zone, defined as the Boundary Watershed Zone was located within the ITZ and had capillaries containing both red and blue microspheres. The width of ITZ was 53377 +/- 817 microns (mean +/- SD), and the width of the BWZ was 3358 +/- 618 microns. Green microspheres, infused into the LCx following coronary occlusion were also found in the ITZ and BWZ. Furthermore, capillaries perfused exclusively by the LAD before occlusion (tissue with red but not blue microspheres) adjacent to the perfusion interface contained green microspheres as well as red/green aggregates, indicating lateral extension of the LCx perfusion territory. This extension of the LCx territory was quantitated by comparing the location at which densities of green microspheres or green/red aggregates decreased abruptly compared to the location of the original ITZ and BWZ boundaries, respectively. Results showed that LAD occlusion caused a 24% expansion of the ITZ and a 48% expansion of the BWZ. In addition, all expansions were significantly greater in subepicardial compared to subendocardial regions (p < 0.001). These results clearly demonstrate the capability of microvascular anastomoses in providing blood flow

  13. Renal Artery Embolization Controls Intractable Pain in a Patient with Polycystic Kidney Disease

    SciTech Connect

    Hahn, Seong Tai; Park, Seog Hee; Lee, Jae Mun; Kim, Choon-Yul; Chang, Yoon Sik

    1999-09-15

    A 65-year-old man with adult polycystic kidney disease (APKD) and chronic renal failure suffered from intractable abdominal pain and distension for 2 weeks. Meperidine infusion did not alleviate his pain. However, pain and abdominal distension were successfully controlled by embolization of both renal arteries.

  14. Implantable, remotely-programmable insulin infusion system

    SciTech Connect

    Carlson, G.A.; Bair, R.E.; Gaona, J.I. Jr.; Love, J.T.; Urenda, R.S.

    1981-10-01

    An implantable, remotely-programmable insulin infusion system is described which has a mass of 280 grams and an implanted lifetime exceeding two years. The system uses a rotary solenoid-driven peristaltic pump controlled by low power CMOS timing circuitry which provides bimodal insulin delivery. Fifteen low rates from 0.39 to 5.9 units/hour and 15 high doses from 0.84 to 12.5 units are available using U100 insulin. The system has been tested in the laboratory, evaluated in diabetic dogs, and implanted in one diabetic human.

  15. MRI Visible Drug Eluting Magnetic Microspheres for Transcatheter Intra-Arterial Delivery to Liver Tumors

    PubMed Central

    Kim, Dong-Hyun; Chen, Jeane; Omary, Reed A.; Larson, Andrew C.

    2015-01-01

    Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies. A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion. This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes. PMID:25767615

  16. Interactions between CO2 chemoreflexes and arterial baroreflexes.

    PubMed

    Henry, R A; Lu, I L; Beightol, L A; Eckberg, D L

    1998-06-01

    We studied interactions between CO2 chemoreflexes and arterial baroreflexes in 10 supine healthy young men and women. We measured vagal carotid baroreceptor-cardiac reflexes and steady-state fast Fourier transform R-R interval and photoplethysmographic arterial pressure power spectra at three arterial pressure levels (nitroprusside, saline, and phenylephrine infusions) and three end-tidal CO2 levels (3, 4, and 5%, fixed-frequency, large-tidal-volume breathing, CO2 plus O2). Our study supports three principal conclusions. First, although low levels of CO2 chemoreceptor stimulation reduce R-R intervals and R-R interval variability, statistical modeling suggests that this effect is indirect rather than direct and is mediated by reductions of arterial pressure. Second, reductions of R-R intervals during hypocapnia reflect simple shifting of vagally mediated carotid baroreflex responses on the R-R interval axis rather than changes of baroreflex gain, range, or operational point. Third, the influence of CO2 chemoreceptor stimulation on arterial pressure (and, derivatively, on R-R intervals and R-R interval variability) depends critically on baseline arterial pressure levels: chemoreceptor effects are smaller when pressure is low and larger when arterial pressure is high. PMID:9841543

  17. Hemodynamic effects of target-controlled infusion of propofol alone or in combination with a constant-rate infusion of remifentanil in dogs

    PubMed Central

    Beier, Suzane L.; Mattoso, Cláudio R.S.; Aguiar, Antonio J.A.; Vianna, Pedro T.G.; Massone, Flavio

    2015-01-01

    The objective of this study was to evaluate the hemodynamic effects of target-controlled infusion (TCI) of propofol alone or in combination with a constant-rate infusion (CRI) of remifentanil. Six adult dogs were given 2 treatments in a randomized crossover study with a 7-day interval between treatments. Treatment 1 was propofol (P) and treatment 2 was propofol and remifentanil (P-Rem), without any premedication. Propofol was induced using a TCI system with a predicted plasma concentration (Cp) of 6.0 μg/mL. Anesthesia was maintained within the Cp range (0.65 to 3.0 μg/mL) for 120 min and remifentanil was administered at a rate of 0.3 μg/kg body weight (BW) per minute, CRI. Cardiopulmonary variables were recorded before (baseline), during, and 120 min after drug administration. Heart rate (HR) decreased significantly in the P-Rem group (46%) compared with baseline values. In the P-Rem group, the cardiac index (CI) decreased significantly (49% to 58%) and the stroke volume (SV) decreased compared with baseline values. The systemic vascular resistance index (SVRI) increased significantly in the P-Rem group compared with baseline values. There was no difference in mean arterial pressure (MAP) between the groups. Central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) significantly increased in the P-Rem group compared with baseline values. In conclusion, the hemodynamic changes observed in this study indicate a compromise of the cardiovascular system, although the dogs in this study were healthy/euvolemic and there was no change in preload. More studies are required in order to evaluate the actual safety of the combination of propofol and remifentanil in patients with reduced cardiac reserve. PMID:26424912

  18. The human urokinase-plasminogen activator gene (PLAU) is located on chromosome 10q24 centromeric to the HOX11 gene

    SciTech Connect

    Stein, P.M.; Stass, S.A.; Kagan, J. )

    1993-04-01

    Urokinase-plasminogen activator is one of two soluble serine proteases that are produced by humans and that convert plasminogen, an inactive proenzyme present in plasma and other extracellular fluids, to plasmin, a protease with broad substrate specificities. Its activity is involved in processes requiring localized extracellular proteolysis such as fibrinolysis, tissue remodeling, and cell migration. Increased production of urokinase has been associated with cancer metastases. The gene for urokinase-plasminogen activator, PLAU, was mapped to chromosome 10q24-qter. By employing somatic cell genetics, polymerase chain reaction (PCR), and Southern blot analysis, the authors assign PLAU to chromosome 10q24. Human chromosome segment 10q23-q25 contains the genes for terminal deoxynucleotidyltransferase, cytochrome P450IIC, glutamic-oxaloacetic transaminase, and plasma retinol binding protein, which form a syntenic group on murine chromosome 19. It is therfore of interest that PLAU and glutamate dehydrogenase, which are on murine chromosome 14, also map in or close to this region of human chromosome 10.

  19. ApaL1 urokinase and Taq1 vitamin D receptor gene polymorphisms in first-stone formers, recurrent stone formers, and controls in a Caucasian population.

    PubMed

    Aykan, Serdar; Tuken, Murat; Gunes, Sezgin; Akin, Yigit; Ozturk, Murat; Seyhan, Serkan; Yuruk, Emrah; Temiz, Mustafa Zafer; Yılmaz, Ali Faik; Nguyen, Daniel P

    2016-04-01

    The purpose of this study was to determine differences in genotype distribution and allele frequency of urokinase and vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) between first-stone formers, recurrent stone formers, and controls in a Caucasian population. A total of 86 first-stone formers, 78 recurrent stone formers, and 167 controls were included. Urokinase and VDR SNPs were tested by gene amplification followed by ApaL1 and Taq1 endonuclease digestion, respectively. Baseline variables, genotype, and allele frequencies were compared between the three groups, using descriptive statistics. Adjusted odds ratios were calculated to estimate the risk for recurrent urolithiasis associated with genotypes. We found that differences in the distribution of ApaL1 SNP and Taq1 SNP genotypes were statistically different between recurrent stone formers and first-stone formers, and between recurrent stone formers and controls. Allele frequency analysis showed that the T allele for ApaL1 SNP and the C allele for Taq1 SNP were significantly associated with recurrent urolithiasis. For Taq1 SNP, logistic regression analysis showed that the C/C genotype was associated with a more than threefold higher risk for recurrent urolithiasis. We conclude that ApaL1 and Taq1 SNPs of the urokinase and VDR genes are associated with recurrent urolithiasis in a Caucasian population. PMID:26275878

  20. Supercritical Fluid Infusion of Iron Additives in Polymeric Matrices

    NASA Technical Reports Server (NTRS)

    Nazem, Negin; Taylor, Larry T.

    1999-01-01

    The objective of this project was the experimentation to measure preparation of iron nanophases within polymeric matrices via supercritical fluid infusion of iron precursors followed by thermal reduction. Another objective was to determine if supercritical CO2 could infuse into the polymer. The experiment is described along with the materials, and the supercritical fluid infusion and cure procedures. X-ray photoelectron spectra and transmission electron micrographs were obtained. The results are summarized in charts, and tables.

  1. Cooled artery extension

    NASA Technical Reports Server (NTRS)

    Gernert, Nelson J. (Inventor)

    1990-01-01

    An artery vapor trap. A heat pipe artery is constructed with an extension protruding from the evaporator end of the heat pipe beyond the active area of the evaporator. The vapor migrates into the artery extension because of gravity or liquid displacement, and cooling the extension condenses the vapor to liquid, thus preventing vapor lock in the working portion of the artery by removing vapor from within the active artery. The condensed liquid is then transported back to the evaporator by the capillary action of the artery extension itself or by wick located within the extension.

  2. Theophylline: constant-rate infusion predictions.

    PubMed

    Mesquita, C A; Sahebjami, H; Imhoff, T; Thomas, J P; Myre, S A

    1984-01-01

    This study was undertaken to evaluate a method of prospectively estimating appropriate aminophylline infusion rates in acutely ill, hospitalized patients with bronchospasm. Steady-state serum theophylline concentrations (Css), clearances (Cl), and half-lives (t1/2) were estimated by the Chiou method using serum concetrantions obtained 1 and 6 h after the start of a constant-rate intravenous aminophylline infusion in 10 male patients averaging 57 years of age. Using an enzyme-multiplied immunoassay (EMIT) system for theophylline analysis, pharmacokinetic estimations were excellent for Css (r = 0.9103, p less than 0.01) and Cl (r = 0.9750, p less than 0.01). The mean estimation errors were 9.4% (range 0.8-21.5) for Css and 12.3% (range 1.3-28.0) for Cl. There was no correlation between patient age and Cl. This method is useful for rapidly individualizing aminophylline therapy in patients with acute bronchospasm. PMID:6740734

  3. Stability of thyroid hormones during continuous infusion.

    PubMed

    Golombek, Sergio G; Alpan, Gad; Frey, Michael; Corbi, Dominick; Lagamma, Edmund F

    2011-07-01

    We investigated the stability of thyroid hormones during a mode of continuous drug infusion via polypropylene tubing using the same conditions that would be applied to treating patients in a hospital setting. The diluted thyroid hormones were prepared using aseptic technique, stored at 2-8°C (36-46°F) and tested within 24 h of preparation for stability and percent recovery from within plastic tubing. Experiments were done in duplicate with triplicate sets of readings for each assay point. Only T(4) prepared with 5% dextrose water (D5W) containing 1 mg/mL albumin remained constant, stable, predictable and accurate over time under various conditions. Other methods of preparation lost drug by adhering to the plastic containers and tubing by as much as 40% of starting concentration. T(3) recovery in the presence of 1 mg/mL of albumin was 107±2% (mean±standard error of the mean) of anticipated drug concentrations. We conclude from this series of experiments that to maintain an accurate and stable dosing of patients receiving intravenous thyroid hormones, 1 mg/mL of albumin must be added to the infusate to prevent lost on the plastic intravenous tubing. PMID:21501101

  4. Implantable Micropump Technologies for Murine Intracochlear Infusions

    PubMed Central

    Johnson, D. G.; Waldron, M. J.; Frisina, R. D.; Borkholder, D. A.

    2011-01-01

    Due to the very small size of the mouse inner ear, 600 nL volume, developing effective, controlled infusion systems is quite challenging. Key technologies have been created to minimize both size and power for an implantable pump for murine intracochlear infusions. A method for coupling fine capillary tubing to microfluidic channels is presented which provides low volume, biocompatible interconnects withstanding pressures as high as 827 kPa (120 psi) and consuming less than 20 nL of volume exiting in-plane with the pump. Surface micromachined resistive bridges integrated into the flow channel for anemometry based flow rate measurement have been optimized for low power operation in the ultra-low flow rate regime. A process for creation of deformable diaphragms over pump chambers with simultaneous coating of the microfluidic channels has been developed allowing integration of a biocompatible fluid flow path. These advances represent enabling capabilities for a drug delivery system suitable for space constrained applications such as subcutaneous implantation in mice. PMID:21096713

  5. Drag reduction using slippery liquid infused surfaces

    NASA Astrophysics Data System (ADS)

    Hultmark, Marcus; Stone, Howard; Smits, Alexander; Jacobi, Ian; Samaha, Mohamed; Wexler, Jason; Shang, Jessica; Rosenberg, Brian; Hellström, Leo; Fan, Yuyang

    2013-11-01

    A new method for passive drag reduction is introduced. A surface treatment inspired by the Nepenthes pitcher plant, previously developed by Wong et al. (2011), is utilized and its design parameters are studied for increased drag reduction and durability. Nano- and micro-structured surfaces infused with a lubricant allow for mobility within the lubricant itself when the surface is exposed to flow. The mobility causes slip at the fluid-fluid interface, which drastically reduces the viscous friction. These new surfaces are fundamentally different from the more conventional superhydrophobic surfaces previously used in drag reduction studies, which rely on a gas-liquid interface. The main advantage of the liquid infused surfaces over the conventional surfaces is that the lubricant adheres more strongly to the surface, decreasing the risk of failure when exposed to turbulence and other high-shear flows. We have shown that these surfaces can reduce viscous drag up to 20% in both Taylor-Couette flow and in a parallel plate rheometer. Supported under ONR Grants N00014-12-1-0875 and N00014-12-1-0962 (program manager Ki-Han Kim).

  6. Intravenous pamidronate: infusion rate and safety.

    PubMed

    Tyrrell, C J; Collinson, M; Madsen, E L; Ford, J M; Coleman, T

    1994-01-01

    In view of previous animal studies showing that pamidronate (Aredia) can cause renal damage, and human data indicating that pamidronate in doses of 60-90 mg is more effective in the control of tumor-induced hypercalcemia than when given at lower doses, we decided to investigate whether pamidronate 90 mg infused over 60 minutes at weekly intervals had any adverse effects on renal function in patients with bone metastases. Twelve patients, 7 female (all with breast cancer) and 5 male (4 with prostate cancer, 1 with bladder cancer) were entered into the trial. Each patient received weekly intravenous infusions of pamidronate 90 mg in 250 ml normal saline over 60 minutes for 4 weeks. 51Cr-EDTA clearances showed no significant changes in renal function. Urinary N-acetyl-B-D-glucosaminidase/creatinine ratios fluctuated considerably, but no consistent changes were found. No patient with a normal level of urinary beta 2-microglobulin had elevated levels at the end of the trial. Serum creatinine levels did not change significantly, though 1 patient had a corrected serum calcium level of < 2 mmol/L on a single occasion on day 8. No evidence of renal toxicity was detected. However, the possibility that neprohtoxicity would ultimately appear cannot be excluded, and these favourable short-term results cannot be extrapolated to patients with impaired renal function. PMID:7873459

  7. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

    Giers, Günther; Wenzel, Folker; Stockschläder, Markus; Riethmacher, Regina; Lorenz, Horst; Tutschek, Boris

    2010-01-01

    Background Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and Methods We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. Results There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×109/L and 130×109/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. Conclusions In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions. PMID:20534698

  8. Broadening infusion specialization as an adjunct to organizational sustainability.

    PubMed

    Meyer, Britt M

    2014-01-01

    As changes in reimbursement structures create a stringent focus on the prevention of infection and other infusion-related complications that predispose to infection, it becomes important to examine the impact of vascular access and infusion specialty practices and procedures on overall organization sustainability and to implement strategies for disseminating infusion expertise to a broader contingent of nurses. This article discusses infusion nursing practice as it impacts the organization as a whole and details a performance improvement initiative for implementing a novel peripherally inserted central catheter tip determination technology that encompasses many of the goals of the industry standards. PMID:24384884

  9. Treatment of subclavian artery stenosis: A case series

    PubMed Central

    Salman, Reem; Hornsby, Jane; Wright, Lucie J.; Elsaid, Tarek; Timmons, Grace; Mudawi, Ahmed; Bhattacharya, Vish

    2015-01-01

    Introduction In this case series, different modalities of treatment for patients with ischaemic symptoms of subclavian stenosis are described, including the different operative strategies that can be adopted in more challenging cases. This is the first case series describing these four management options. Presentation Case 1: A seventy-one year-old female presented with acute on chronic ischaemia of her left arm following a fall and developed dry gangrene of her left thumb. This was initially managed with a heparin infusion followed by stenting of the subclavian artery which relieved her symptoms. Case 2: A fifty-nine year-old male presented with chronic ischemia of the left arm secondary to an occlusion of the left subclavian artery. This was managed by transposition of the left subclavian artery onto the left common carotid artery. Case 3: A sixty-four year-old female presented with left subclavian steal syndrome secondary to subclavian artery stenosis. She underwent carotid subclavian artery bypass. Case 4: A fifty-six year-old female presented with acute left upper limb ischaemia secondary to acutely thrombosed subclavian artery on a CT-angiography. She underwent a carotid to axillary bypass. Discussion and conclusion This case series demonstrates the treatment options available to vascular surgeons when managing symptomatic subclavian artery disease. Symptomatic subclavian artery occlusive disease should be treated with endovascular stenting and angioplasty as first line management. If it is not successful then open surgery should be considered. Bypassing the carotid to the subclavian or to the axillary artery are both good treatment modalities. PMID:26722712

  10. Effect of abomasal infusion of oligofructose on portal-drained visceral ammonia and urea-nitrogen fluxes in lactating Holstein cows.

    PubMed

    Røjen, B A; Larsen, M; Kristensen, N B

    2012-12-01

    The effects of abomasal infusion of oligofructose in lactating dairy cows on the relationship between hindgut fermentation and N metabolism, and its effects on NH(3) absorption and transfer of blood urea-N across the portal-drained viscera versus ruminal epithelia were investigated. Nine lactating Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in major splanchnic blood vessels were used in an unbalanced crossover design with 14-d periods. Treatments were continuous abomasal infusion of water or 1,500 g/d of oligofructose. The same basal diet was fed with both treatments. Eight sample sets of arterial, portal, hepatic, and ruminal vein blood, ruminal fluid, and urine were obtained at 0.5h before the morning feeding and at 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 h after feeding. It was hypothesized that an increased supply of fermentable substrate to the hindgut would increase the uptake of urea-N from blood to the hindgut at the expense of urea-N uptake to the forestomach. The study showed that abomasal oligofructose infusion decreased the total amount of urea-N transferred from the blood to the gut, NH(3) absorption, and arterial blood urea-N concentration. Subsequently, hepatic NH(3) uptake and urea-N production also decreased with oligofructose infusion. Additionally, urea-N concentration in milk and urinary N excretion decreased with oligofructose treatment. The oligofructose infusion did not affect ruminal NH(3) concentrations or any other ruminal variables, nor did it affect ruminal venous - arterial concentration differences for urea-N and NH(3). The oligofructose treatment did not affect milk yield, but did decrease apparent digestibility of OM, N, and starch. Nitrogen excreted in the feces was greater with the oligofructose infusion. In conclusion, the present data suggest that increased hindgut fermentation did not upregulate urea-N transfer to the hindgut at the expense of urea-N uptake by the rumen, and the observed reduction

  11. Cardiovascular and endocrine responses to acute hypoxaemia during and following dexamethasone infusion in the ovine fetus

    PubMed Central

    Fletcher, Andrew J W; Gardner, David S; Edwards, C Mark B; Fowden, Abigail L; Giussani, Dino A

    2003-01-01

    This study investigated the effects of fetal treatment with dexamethasone on ovine fetal cardiovascular defence responses to acute hypoxaemia, occurring either during or 48 h following the period of glucocorticoid exposure. To address the mechanisms underlying these responses, chemoreflex function and plasma concentrations of catecholamines, neuropeptide Y (NPY) and vasopressin were measured. Under general halothane anaesthesia, 26 Welsh Mountain sheep fetuses were surgically prepared for long-term recording at between 117 and 120 days of gestation (dGA; term is ∼145 days) with vascular catheters and a Transonic flow probe around a femoral artery. Following at least 5 days of recovery, fetuses were randomly assigned to one of two experimental groups. After 48 h of baseline recording, at 125 ± 1 dGA, half of the fetuses (n = 13) were continuously infused i.v. with dexamethasone for 48 h at a rate of 2.06 ± 0.13 μg kg−1 h−1. The remaining 13 fetuses were infused with heparinized saline at the same rate (controls). At 127 ± 1 dGA, 2 days from the onset of infusions, seven fetuses from each group were subjected to 1 h of acute hypoxaemia. At 129 ± 1 dGA, 2 days after the end of infusions, six fetuses from each group were subjected to 1 h of acute hypoxaemia. Similar reductions in fetal partial pressure of arterial oxygen occurred in control and dexamethasone-treated fetuses during the acute hypoxaemia protocols. In control fetuses, acute hypoxaemia led to transient bradycardia, femoral vasoconstriction and significant increases in plasma concentrations of catecholamines, vasopressin and NPY. In fetuses subjected to acute hypoxaemia during dexamethasone treatment, the increase in plasma NPY was enhanced, the bradycardic response was prolonged, and the plasma catecholamine and vasopressin responses were diminished. In fetuses subjected to acute hypoxaemia 48 h following dexamethasone treatment, femoral vasoconstriction and plasma catecholamine and vasopressin

  12. Coronary Artery Disease

    MedlinePlus

    Coronary artery disease (CAD) is the most common type of heart disease. It is the leading cause of death ... both men and women. CAD happens when the arteries that supply blood to heart muscle become hardened ...

  13. Occlusive Peripheral Arterial Disease

    MedlinePlus

    ... artery. Such people should seek medical care immediately. Did You Know... When people suddenly develop a painful, ... In This Article Animation 1 Peripheral Arterial Disease Did You Know 1 Did You Know... Figure 1 ...

  14. Retinal artery occlusion

    MedlinePlus

    ... These blockages are more likely if there is hardening of the arteries ( atherosclerosis ) in the eye. Clots ... Blindness and vision loss Blood clots Diabetes Glaucoma Hardening of the arteries High blood cholesterol levels High ...

  15. Coronary Artery Disease

    MedlinePlus

    Coronary artery disease (CAD) is the most common type of heart disease. It is the leading cause of death in the United States in both men and women. CAD happens when the arteries that supply blood to ...

  16. Carotid artery surgery - discharge

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000238.htm Carotid artery surgery - discharge To use the sharing features on this page, please enable JavaScript. You had carotid artery surgery to restore proper blood flow to your ...

  17. Carotid artery surgery - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100124.htm Carotid artery surgery - series To use the sharing features on ... 4 Normal anatomy Overview There are four carotid arteries, with a pair located on each side of ...

  18. Coronary artery fistula

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/007315.htm Coronary artery fistula To use the sharing features on this page, please enable JavaScript. Coronary artery fistula is an abnormal connection between one of ...

  19. Peripheral Artery Disease (PAD)

    MedlinePlus

    ... changes and medication . View an animation of atherosclerosis Atherosclerosis and PAD Atherosclerosis is a disease in which plaque builds up ... of an artery. PAD is usually caused by atherosclerosis in the peripheral arteries (or outer regions away ...

  20. Coronary artery disease

    MedlinePlus Videos and Cool Tools

    ... heart muscle itself. Damage to or blockage of a coronary artery can result in injury to the heart. Normally, blood flows through a coronary artery unimpeded. However, a process called atherosclerosis ...

  1. Combination of Rare Right Arterial Variation with Anomalous Origins of the Vertebral Artery, Aberrant Subclavian Artery and Persistent Trigeminal Artery

    PubMed Central

    Ishihara, H.; San Millán Ruíz, D.; Abdo, G.; Asakura, F.; Yilmaz, H.; Lovblad, K.O.; Rüfenacht, D.A.

    2011-01-01

    Summary A 32-year-old woman hospitalized for subarachnoid hemorrhage showed rare arterial variation on the right side with anomalous origins of the vertebral artery, aberrant subclavian artery and persistent trigeminal artery. Angiography showed the right vertebral artery to originate from the right common carotid artery, the right subclavian artery to arise separately from the descending aorta, and persistent trigeminal artery on the right side. The possible embryonic mechanism of this previously unreported variant combination is discussed. PMID:22005696

  2. Carotid Artery Disease

    MedlinePlus

    ... and efficacy continues to be studied in several medical centers. This procedure involves the placement of a small flexible tube (catheter) into an artery from the groin. The catheter is then directed to the neck to reach the carotid artery blockage. A balloon pushes open the artery wall and a stent ( ...

  3. Infused polymers for cell sheet release

    NASA Astrophysics Data System (ADS)

    Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

    2016-05-01

    Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering.

  4. Infused polymers for cell sheet release

    PubMed Central

    Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L.; Lin, Jennifer J.; Sutton, Amy; Aizenberg, Joanna

    2016-01-01

    Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering. PMID:27189419

  5. Infused polymers for cell sheet release.

    PubMed

    Juthani, Nidhi; Howell, Caitlin; Ledoux, Haylea; Sotiri, Irini; Kelso, Susan; Kovalenko, Yevgen; Tajik, Amanda; Vu, Thy L; Lin, Jennifer J; Sutton, Amy; Aizenberg, Joanna

    2016-01-01

    Tissue engineering using whole, intact cell sheets has shown promise in many cell-based therapies. However, current systems for the growth and release of these sheets can be expensive to purchase or difficult to fabricate, hindering their widespread use. Here, we describe a new approach to cell sheet release surfaces based on silicone oil-infused polydimethylsiloxane. By coating the surfaces with a layer of fibronectin (FN), we were able to grow mesenchymal stem cells to densities comparable to those of tissue culture polystyrene controls (TCPS). Simple introduction of oil underneath an edge of the sheet caused it to separate from the substrate. Characterization of sheets post-transfer showed that they retain their FN layer and morphology, remain highly viable, and are able to grow and proliferate normally after transfer. We expect that this method of cell sheet growth and detachment may be useful for low-cost, flexible, and customizable production of cellular layers for tissue engineering. PMID:27189419

  6. Direct infusion of a variant of insulin-like growth factor-I into the skin of sheep and effects on local blood flow, amino acid utilization and cell replication.

    PubMed

    Harris, P M; McBride, B W; Gurnsey, M P; Sinclair, B R; Lee, J

    1993-12-01

    In vivo effects of local infusion of a variant of insulin-like growth factor-I (IGF-I), long-R3-IGF-I, into the skin were investigated using six conscious sheep with food available ad libitum. An artery and vein on the abdominal flank of each animal, as well as the saphenous artery, were catheterized so that infusion of isotopically labelled amino acids, with or without IGF-I, could be used to determine amino acid uptake by arteriovenous difference in combination with blood flow determined by dye dilution. Measurements were made on each animal prior to IGF-I infusion, at hourly intervals for the 4 h of IGF-I infusion into the skin artery, then 2 and 4 h after IGF-I infusion ceased. Numbers of cells replicating in the bulbs of wool follicles in the IGF-I-infused area and in the skin on the contralateral side of each animal were measured after labelling with 5-bromo-2'-deoxyuridine. IGF-I caused a significant increase in the skin blood flow (P < 0.05), utilization of oxygen (P < 0.05), uptake of cysteine (P < 0.05) and phenylalanine (P < 0.001), and the rate of utilization of cysteine (P < 0.05) for protein synthesis. IGF-I increased amino acid uptake regardless of whether the skin was in negative or positive amino acid balance prior to infusion. During the recovery period amino acid utilization by skin returned towards preinfusion levels. No effects of IGF-I were found on replicating cell numbers in the bulbs of wool follicles. PMID:8133213

  7. Aortic Input Impedance during Nitroprusside Infusion

    PubMed Central

    Pepine, Carl J.; Nichols, W. W.; Curry, R. C.; Conti, C. Richard

    1979-01-01

    Beneficial effects of nitroprusside infusion in heart failure are purportedly a result of decreased afterload through “impedance” reduction. To study the effect of nitroprusside on vascular factors that determine the total load opposing left ventricular ejection, the total aortic input impedance spectrum was examined in 12 patients with heart failure (cardiac index <2.0 liters/min per m2 and left ventricular end diastolic pressure >20 mm Hg). This input impedance spectrum expresses both mean flow (resistance) and pulsatile flow (compliance and wave reflections) components of vascular load. Aortic root blood flow velocity and pressure were recorded continuously with a catheter-tip electromagnetic velocity probe in addition to left ventricular pressure. Small doses of nitroprusside (9-19 μg/min) altered the total aortic input impedance spectrum as significant (P < 0.05) reductions in both mean and pulsatile components were observed within 60-90 s. With these acute changes in vascular load, left ventricular end diastolic pressure declined (44%) and stroke volume increased (20%, both P < 0.05). Larger nitroprusside doses (20-38 μg/min) caused additional alteration in the aortic input impedance spectrum with further reduction in left ventricular end diastolic pressure and increase in stroke volume but no additional changes in the impedance spectrum or stroke volume occurred with 39-77 μg/min. Improved ventricular function persisted when aortic pressure was restored to control values with simultaneous phenylephrine infusion in three patients. These data indicate that nitroprusside acutely alters both the mean and pulsatile components of vascular load to effect improvement in ventricular function in patients with heart failure. The evidence presented suggests that it may be possible to reduce vascular load and improve ventricular function independent of aortic pressure reduction. PMID:457874

  8. The half-life of infusion fluids

    PubMed Central

    Hahn, Robert G.; Lyons, Gordon

    2016-01-01

    An understanding of the half-life (T1/2) of infused fluids can help prevent iatrogenic problems such as volume overload and postoperative interstitial oedema. Simulations show that a prolongation of the T1/2 for crystalloid fluid increases the plasma volume and promotes accumulation of fluid in the interstitial fluid space. The T1/2 for crystalloids is usually 20 to 40 min in conscious humans but might extend to 80 min or longer in the presence of preoperative stress, dehydration, blood loss of <1 l or pregnancy. The longest T1/2 measured amounts to between 3 and 8 h and occurs during surgery and general anaesthesia with mechanical ventilation. This situation lasts as long as the anaesthesia. The mechanisms for the long T1/2 are only partly understood, but involve adrenergic receptors and increased renin and aldosterone release. In contrast, the T1/2 during the postoperative period is usually short, about 15 to 20 min, at least in response to new fluid. The commonly used colloid fluids have an intravascular persistence T1/2 of 2 to 3 h, which is shortened by inflammation. The fact that the elimination T1/2 of the infused macromolecules is 2 to 6 times longer shows that they also reside outside the bloodstream. With a colloid, fluid volume is eliminated in line with its intravascular persistence, but there is insufficient data to know if this is the same in the clinical setting. PMID:27058509

  9. Infusing the Workplace into General ABE/GED/ESL Programs.

    ERIC Educational Resources Information Center

    Thistlethwaite, Linda

    2000-01-01

    This paper explains how adult educators involved in the development and delivery of general adult basic education (ABE), General Educational Development (GED) certificate, and English-as-a-second-language (ESL) programs can infuse the workplace into their programs. The paper begins with a brief overview of the rationale for infusing the workplace…

  10. 21 CFR 529.1044a - Gentamicin solution for infusion.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin solution for infusion. 529.1044a... Gentamicin solution for infusion. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000061, 000859, 054628, 054771, 057561, 058005,...

  11. Silos to Symphonies? Hopes and Challenges Implementing Multicultural Programme Infusion

    ERIC Educational Resources Information Center

    Liu, Laura B.; Milman, Natalie B.

    2013-01-01

    The need to infuse multicultural education (ME) across teacher preparation programmes is well documented by research, yet institutions are at very different stages in this endeavour. While most programmes demonstrate a segregated approach to ME, confining diversity to specialty courses, ME programme infusion places diversity, equity and social…

  12. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Hetacillin potassium for intramammary infusion... Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See No. 000010 in §...

  13. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hetacillin potassium for intramammary infusion... § 526.1130 Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See...

  14. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hetacillin potassium for intramammary infusion... § 526.1130 Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See...

  15. 21 CFR 526.1130 - Hetacillin potassium for intramammary infusion.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Hetacillin potassium for intramammary infusion... § 526.1130 Hetacillin potassium for intramammary infusion. (a) Specifications. Each 10 milliliter syringe contains hetacillin potassium equivalent of 62.5 milligrams of ampicillin. (b) Sponsor. See...

  16. Energy Management for School Administrators: Curriculum Infusion Facilities Audit.

    ERIC Educational Resources Information Center

    Education Service Center Region 7, Kilgore, TX.

    Presented are the state guidelines and framework for the infusion of energy education into the Texas public school curriculum. Designed to assist teachers, administrators, and other school personnel in the process of infusing energy education concepts, this guide focuses on the basic concerns and needs of the people as related to energy and…

  17. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  18. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  19. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  20. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  1. 21 CFR 870.1800 - Withdrawal-infusion pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Withdrawal-infusion pump. 870.1800 Section 870.1800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately...

  2. ArtsIN: Arts Integration and Infusion Framework

    ERIC Educational Resources Information Center

    Hartle, Lynn C.; Pinciotti, Patricia; Gorton, Rebecca L.

    2015-01-01

    Teaching to meet the diverse learning needs of twenty-first century, global learners can be challenging, yet a growing body of research points to the proved successes of arts-infused and integrated curricula, especially for building capacity for learning and motivation. This article presents the ArtsIN: Arts Integration and Infusion framework, a…

  3. [Anatomic repair of transposition of the great arteries or arterial switch operation. Report of 62 cases].

    PubMed

    Abid, Fekria; Chaker, Lilia; Hakim, Khaouther; Larbi, Chiheb; Ouarda, Fatma; Msaad, Hela; Mechmeche, Rachid

    2004-01-01

    Between January 1990 and September 2003, 62 patients underwent anatomic repair of a transposition of the great arteries. Mean operative age is 40 days. Transposition of the great arteries was simple in 38 cases and associated to a large ventricular septal defect in 24 cases. 44 patients have had an atrial septostomy of Rashkind and 45 an infusion of prostaglandin E 1.5 patients with simple transposition of the great arteries have had left ventricular retraining before arteriel switch. In association to arterial switch, were performed closure of ventricular septal defect in 24 cases, cure of coarctation of the aorta in 4 cases and cure of an abnormal partial pulmonary venous return in 1 case. Early mortality was 6,45%. After a mean follow up of 3 years, one patient died suddenly (late mortality is 1.72%) and one patient had to have 2 reoperations. Results of anatomic repair are now excellent. Late mortality is essentially related to coronary complications so that a careful follow-up is mandatory. PMID:15127697

  4. Proximity oscillations of complement type 4 (alphaX beta2) and urokinase receptors on migrating neutrophils.

    PubMed Central

    Kindzelskii, A L; Eszes, M M; Todd, R F; Petty, H R

    1997-01-01

    Migrating neutrophils utilize beta2 integrins for substrate attachment and urokinase receptors (uPAR) to focus pericellular proteolysis. Our studies show that CR3 associates with uPAR on resting cells, whereas uPAR associates with CR4 at lamellipodia of migrating cells. Using resonance energy transfer (RET) microscopy, we show that the molecular proximity between CR4 and uPAR oscillates on migrating cells, thus suggesting that CR4 molecules periodically bind/release uPAR. Cell contact with fibrinogen, endothelial cells, chemotactic factors and indomethacin, and treatment with sub-optimal doses of signal transduction inhibitors, affect the oscillations' period, amplitude, and/or waveform. The oscillations were indistinguishable in period and 180 degrees out-of-phase with cytosolic NAD(P)H autofluorescence oscillations. Thus, CR4 and CR3 identify a neutrophil's axis of migration and CR4 may restrain uPAR at lamellipodia. Oscillations in signal transduction and energy metabolism may coordinate cell adherence, local proteolysis, oxidant release, actin assembly, and cell extension. Images FIGURE 1 PMID:9336173

  5. A high-affinity receptor for urokinase plasminogen activator on human keratinocytes: characterization and potential modulation during migration.

    PubMed Central

    McNeill, H; Jensen, P J

    1990-01-01

    Low passage cultures of normal human keratinocytes produce several components of the plasminogen activator/plasmin proteolytic cascade, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), and two specific inhibitors. Studies here presented demonstrate that these cells also contain a high-affinity (Kd = 3 x 10(-10) M) plasma membrane-binding site for uPA. High molecular weight uPA, either as the single-chain precursor or two-chain activated form, bound to the receptor; however, low molecular weight (33 kD) uPA, tPA, or epidermal growth factor did not compete for binding, demonstrating specificity. Acid treatment, which removed endogenous uPA from the receptor, was required to detect maximal binding (45,000 sites per cell). To investigate the possibility that the uPA receptor on keratinocytes may be involved in epithelial migration during wound repair, cultures were wounded and allowed to migrate into the wounded site. Binding sites for uPA were localized by autoradiographic analysis of 125I-uPA binding as well as by immunocytochemical studies using anti-uPA IgG. With both techniques uPA binding sites were detected selectively on the plasma membrane of cells at the leading edge of the migrating epithelial sheet. This localization pattern suggests that uPA receptor expression on keratinocytes may be coupled to cell migration during cutaneous wounding. Images PMID:1965151

  6. Structure-based Engineering of Species Selectivity in the Interaction Between Urokinase and its Receptor: Implication for Preclinical Cancer Therapy

    SciTech Connect

    Lin, L.; Gardsvoll, H; Huai, Q; Huang, M; Ploug, M

    2010-01-01

    The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) is decisive for cell surface-associated plasminogen activation. Because plasmin activity controls fibrinolysis in a variety of pathological conditions, including cancer and wound healing, several intervention studies have focused on targeting the uPA {center_dot} uPAR interaction in vivo. Evaluations of such studies in xenotransplanted tumor models are, however, complicated by the pronounced species selectivity in this interaction. We now report the molecular basis underlying this difference by solving the crystal structure for the murine uPA {center_dot} uPAR complex and demonstrate by extensive surface plasmon resonance studies that the kinetic rate constants for this interaction can be swapped completely between these orthologs by exchanging only two residues. This study not only discloses the structural basis required for a successful rational design of the species selectivity in the uPA {center_dot} uPAR interaction, which is highly relevant for functional studies in mouse models, but it also suggests the possible development of general inhibitors that will target the uPA {center_dot} uPAR interaction across species barriers.

  7. Zinc phthalocyanine conjugated with the amino-terminal fragment of urokinase for tumor-targeting photodynamic therapy.

    PubMed

    Chen, Zhuo; Xu, Peng; Chen, Jincan; Chen, Hongwei; Hu, Ping; Chen, Xueyuan; Lin, Lin; Huang, Yunmei; Zheng, Ke; Zhou, Shanyong; Li, Rui; Chen, Song; Liu, Jianyong; Xue, Jinping; Huang, Mingdong

    2014-10-01

    Photodynamic therapy (PDT) has attracted much interest for the treatment of cancer due to the increased incidence of multidrug resistance and systemic toxicity in conventional chemotherapy. Phthalocyanine (Pc) is one of main classes of photosensitizers for PDT and possesses optimal photophysical and photochemical properties. A higher specificity can ideally be achieved when Pcs are targeted towards tumor-specific receptors, which may also facilitate specific drug delivery. Herein, we develop a simple and unique strategy to prepare a hydrophilic tumor-targeting photosensitizer ATF-ZnPc by covalently coupling zinc phthalocyanine (ZnPc) to the amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA), a fragment responsible for uPA receptor (uPAR, a biomarker overexpressed in cancer cells), through the carboxyl groups of ATF. We demonstrate the high efficacy of this tumor-targeting PDT agent for the inhibition of tumor growth both in vitro and in vivo. Our in vivo optical imaging results using H22 tumor-bearing mice show clearly the selective accumulation of ATF-ZnPc in tumor region, thereby revealing the great potential of ATF-ZnPc for clinical applications such as cancer detection and guidance of tumor resection in addition to photodynamic treatment. PMID:24969665

  8. Mutation of the protein-O-mannosyltransferase enhances secretion of the human urokinase-type plasminogen activator in Hansenula polymorpha.

    PubMed

    Agaphonov, Michael O; Sokolov, Sviatoslav S; Romanova, Nina V; Sohn, Jung-Hoon; Kim, So-Young; Kalebina, Tatyana S; Choi, Eui-Sung; Ter-Avanesyan, Michael D

    2005-10-15

    Human urokinase-type plasminogen activator (uPA) is poorly secreted and aggregates in the endoplasmic reticulum of yeast cells due to inefficient folding. A screen for Hansenula polymorpha mutants with improved uPA secretion revealed a gene encoding a homologue of the Saccharomyces cerevisiae protein-O-mannosyltransferase Pmt1p. Expression of the H. polymorpha PMT1 gene (HpPMT1) abolished temperature sensitivity of the S. cerevisiae pmt1 pmt2 double mutant. As in S. cerevisiae, inactivation of the HpPMT1 gene affected electrophoretic mobility of the O-glycosylated protein, extracellular chitinase. In contrast to S. cerevisiae, disruption of HpPMT1 alone caused temperature sensitivity. Inactivation of the HpPMT1 gene decreased intracellular aggregation of uPA, suggesting that enhanced secretion of uPA was due to improvement of its folding in the endoplasmic reticulum. Unlike most of the endoplasmic reticulum membrane proteins, HpPmt1p possesses the C-terminal KDEL retention signal. PMID:16200504

  9. Risk factors associated with serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor in a general population.

    PubMed

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line Jh; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  10. Increased Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels in Plasma of Suicide Attempters

    PubMed Central

    Ventorp, Filip; Gustafsson, Anna; Träskman-Bendz, Lil; Westrin, Åsa; Ljunggren, Lennart

    2015-01-01

    The soluble form of the urokinase receptor, suPAR, has been suggested as a novel biomarker of low-grade inflammation. Activation of the immune system has been proposed to contribute to the development of depression and suicidal behavior. In order to identify depressed and suicidal individuals who could benefit from an anti-inflammatory treatment, a reliable biomarker of low-grade inflammation is vital. This study evaluates plasma suPAR levels as a biomarker of low-grade inflammation in patients with major depressive disorder and in patients who recently attempted suicide. The plasma suPAR and an established biomarker, C reactive protein (CRP) of suicide attempters (n = 54), depressed patients (n = 19) and healthy controls (n = 19) was analyzed with enzyme-linked immunosorbent assays. The biomarker attributes of sensitivity and sensibility were evaluated using ROC curve analysis. Both the depressed patients and suicide attempters had increased plasma suPAR. The levels of suPAR discriminated better between controls and suicide attempters than did CRP. In the future, plasma suPAR might be a superior prognosticator regarding outcome of treatment applying conventional antidepressants in conjunction with anti-inflammatory drugs. PMID:26451727

  11. Multifunctional roles of urokinase plasminogen activator (uPA) in cancer stemness and chemoresistance of pancreatic cancer

    PubMed Central

    Asuthkar, Swapna; Stepanova, Victoria; Lebedeva, Tatiana; Holterman, AiXuan L.; Estes, Norman; Cines, Douglas B.; Rao, Jasti S.; Gondi, Christopher S.

    2013-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is almost always lethal. One of the underlying reasons for this lethality is believed to be the presence of cancer stem cells (CSC), which impart chemoresistance and promote recurrence, but the mechanisms responsible are unclear. Recently the poor prognosis of PDAC has been correlated with increased expression of urokinase plasminogen activator (uPA). In the present study we examine the role of uPA in the generation of PDAC CSC. We observe a subset of cells identifiable as a side population (SP) when sorted by flow cytometry of MIA PaCa-2 and PANC-1 pancreatic cancer cells that possess the properties of CSC. A large fraction of these SP cells are CD44 and CD24 positive, are gemcitabine resistant, possess sphere-forming ability, and exhibit increased tumorigenicity, known characteristics of cancer stemness. Increased tumorigenicity and gemcitabine resistance decrease after suppression of uPA. We observe that uPA interacts directly with transcription factors LIM homeobox-2 (Lhx2), homeobox transcription factor A5 (HOXA5), and Hey to possibly promote cancer stemness. uPA regulates Lhx2 expression by suppressing expression of miR-124 and p53 expression by repressing its promoter by inactivating HOXA5. These results demonstrate that regulation of gene transcription by uPA contributes to cancer stemness and clinical lethality. PMID:23864708

  12. Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

    PubMed Central

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line JH; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  13. Transforming Growth Factor-Beta and Urokinase-Type Plasminogen Activator: Dangerous Partners in Tumorigenesis—Implications in Skin Cancer

    PubMed Central

    Santibanez, Juan F.

    2013-01-01

    Transforming growth factor-beta (TGF-β) is a pleiotropic factor, with several different roles in health and disease. TGF-β has been postulated as a dual factor in tumor progression, since it represses epithelial tumor development in early stages, whereas it stimulates tumor progression in advanced stages. During tumorigenesis, cancer cells acquire the capacity to migrate and invade surrounding tissues and to metastasize different organs. The urokinase-type plasminogen activator (uPA) system, comprising uPA, the uPA cell surface receptor, and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and regulates key cellular events by activating intracellular signal pathways, which together allow cancer cells to survive, thus, enhancing cell malignance during tumor progression. Due to their importance, uPA and its receptor are tightly transcriptionally regulated in normal development, but are deregulated in cancer, when their activity and expression are related to further development of cancer. TGF-β regulates uPA expression in cancer cells, while uPA, by plasminogen activation, may activate the secreted latent TGF-β, thus, producing a pernicious cycle which contributes to the enhancement of tumor progression. Here we review the specific roles and the interplay between TGF-β and uPA system in cancer cells and their implication in skin cancer. PMID:23984088

  14. A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease.

    PubMed

    Wada, Takehiko; Nangaku, Masaomi; Maruyama, Shoichi; Imai, Enyu; Shoji, Kumi; Kato, Sawako; Endo, Tomomi; Muso, Eri; Kamata, Kouju; Yokoyama, Hitoshi; Fujimoto, Keiji; Obata, Yoko; Nishino, Tomoya; Kato, Hideki; Uchida, Shunya; Sasatomi, Yoshie; Saito, Takao; Matsuo, Seiichi

    2014-03-01

    Elevated serum-soluble urokinase receptor (suPAR) levels have been described in patients with focal segmental glomerulosclerosis (FSGS) in several different cohorts. However, it remains unclear whether this is the case for Japanese patients and whether circulating suPAR can be clinically useful as a diagnostic marker. To determine this, we measured serum suPAR levels in 69 Japanese patients with biopsy-proven glomerular diseases in a cross-sectional manner. The serum suPAR levels showed a significant inverse correlation with renal function by univariate (R(2) of 0.242) and multivariate (β=0.226) analyses. Even after excluding patients with renal dysfunction, no significant difference in the suPAR levels was detected among the groups. Receiver operating characteristic analysis and measures of the diagnostic test performance showed that suPAR was not a useful parameter for differentiating FSGS from the other glomerular diseases (AUC-ROC: 0.621), although a small subgroup analysis showed that patients with FSGS, treated with steroids and/or immunosuppressants, had significantly lower suPAR levels. Patients with ANCA-associated glomerulonephritis had significantly higher levels of suPAR compared with the other disease groups, which may be owing to their lower renal function and systemic inflammation. Thus, suPAR levels are significantly affected by renal function and have little diagnostic value even in patients with normal renal function. PMID:24429394

  15. [Liver abscess formation after treatment of liver cancer by arterial injection using adriamycin/mitomycin C oil suspension (ADMOS)].

    PubMed

    Inoue, H; Hori, A; Satake, M; Kanetsuki, I; Ueno, K; Nishida, H; Ikeda, K; Kobayashi, H; Nakajo, M

    1992-02-25

    Of 210 patients with hepatocellular carcinoma (n = 135), metastatic liver cancer (n = 71) and cholangiocarcinoma (n = 4) who underwent intra-arterial infusion of adriamycin and/or mitomycin C oil suspension (ADMOS) and cisplatin, and both regimens, pyogenic liver abscess occurred in seven (3.3%). The percentages of abscess formation in the respective types of liver cancer were 0.8, 7.0 and 25%. These differences among the three types of liver cancer were attributed to the volume of the tumor vascular beds to be embolized, which might determine the relative amount or regional Lipiodol retention in the tumor and normal liver tissue. Four of seven patients with hepatic abscess had received the intra-arterial infusion of ADMOS, and their angiographic findings showed sequential decreases in the vascular beds of the tumor in comparison with those of previous infusion procedures; all had hypovascular liver tumors angiographically. We have never experienced this complication in other treatments such as embolization of the hepatic arteries and intra-arterial infusion of water-soluble anticancer drugs alone. These results suggest that the most important factor leading to abscess formation is the ischemic destruction of the intrahepatic ducts secondary to occlusion of the peribiliary arterial plexus by Lipiodol and/or the direct effects of anticancer drugs on these vessels. To avoid this complication, the volume of Lipiodol used for intraarterial infusion therapy should be carefully determined, especially when the patient has hypovascular tumors of the liver and a history of multiple previous intraarterial infusion procedures of anticancer drug. The use of ADMOS should be avoided in patients with hypovascular tumors of the liver such as secondary deposits and cholangiocarcinoma. PMID:1313961

  16. Jet pump assisted artery

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A procedure for priming an arterial heat pump is reported; the procedure also has a means for maintaining the pump in a primed state. This concept utilizes a capillary driven jet pump to create the necessary suction to fill the artery. Basically, the jet pump consists of a venturi or nozzle-diffuser type constriction in the vapor passage. The throat of this venturi is connected to the artery. Thus vapor, gas, liquid, or a combination of the above is pumped continuously out of the artery. As a result, the artery is always filled with liquid and an adequate supply of working fluid is provided to the evaporator of the heat pipe.

  17. External artery heat pipe

    NASA Technical Reports Server (NTRS)

    Gernert, Nelson J. (Inventor); Ernst, Donald M. (Inventor); Shaubach, Robert M. (Inventor)

    1989-01-01

    An improved heat pipe with an external artery. The longitudinal slot in the heat pipe wall which interconnects the heat pipe vapor space with the external artery is completely filled with sintered wick material and the wall of the external artery is also covered with sintered wick material. This added wick structure assures that the external artery will continue to feed liquid to the heat pipe evaporator even if a vapor bubble forms within and would otherwise block the liquid transport function of the external artery.

  18. Acute Arterial Emergencies

    PubMed Central

    Dagnone, L. E.; Brown, P. M.

    1983-01-01

    The response of the primary care physician in the initial assessment and management of acute arterial injuries will often be the deciding factor in survival of life, limb or organ system. Most arterial emergencies occur as a result of trauma, disruption of vessel wall and/or occlusion of flow. The common clinical syndromes of acute arterial emergencies are injuries to and beyond the aorta, acute aortic dissection, ruptured aortic aneurysm, and thromboembolic occlusive arterial disease. The role of arteriography and the urgency of definitive surgical repair in acute arterial emergencies is summarized. PMID:21283323

  19. Combined hormonal infusion simulates the metabolic response to injury.

    PubMed Central

    Bessey, P Q; Watters, J M; Aoki, T T; Wilmore, D W

    1984-01-01

    To investigate the role of hormones as mediators of the metabolic response to injury, nine normal male volunteers received a continuous 74-hour infusion of the three 'stress' hormones: cortisol, glucagon, and epinephrine. As a control, each subject received a saline infusion during another 4-day period. Diets were constant and matched on both occasions. Hormonal infusion achieved hormone concentrations similar to those seen following mild-moderate injury. With this alteration in the endocrine environment significant hypermetabolism, negative nitrogen and potassium balances, glucose intolerance, hyperinsulinemia, insulin resistance, sodium retention, and peripheral leukocytosis were observed. Additional studies with single hormone infusions indicated that these responses resulted from both additive and synergistic interactions of the hormones. Triple hormone infusion simulated many of the metabolic responses observed following mild-moderate injury and other catabolic illnesses. PMID:6431917

  20. Splanchnic net balance of oxygen and metabolites in response to a discontinuous mesenteric vein infusion of ammonium in sheep.

    PubMed

    Recavarren, M I; Milano, G D

    2013-12-01

    To simulate daily episodes of high absorption associated with the intake of diets with high N content, four wethers (42 ± 3.4 kg body weight), fitted with permanent catheters in the femoral artery and splanchnic vessels, were infused with 340 μmol into the mesenteric vein for 3 h, during the morning meal, over seven consecutive days. On the 7th day, mass transfers of , urea, glucose, lactate, ß-OH-butyrate and O2 were measured across portal-drained viscera (PDV), liver and splanchnic tissues during the last 90 min of the infusion. Measurements were repeated on the following day, at the same time, without the infusion. Plasma concentration in the portal vein (+332 μm; p = 0.006), portal absorption (+424 μmol/min; p < 0.001), liver uptake (+375 μmol/min; p = 0.003) and urea N production (+338 μmol/min; p = 0.059) were higher during infusion. Mass transfers of urea, glucose, lactate, ß-OH-butyrate and O2 across the PDV, and glucose, lactate, ß-OH-butyrate and O2 across the liver, were not altered by the infusion. Results suggest that a daily, discontinuous increase in portal flow during a meal stimulates liver removal and urea N production but does not significantly affect liver glucose production and O2 consumption in sheep. PMID:23005900

  1. Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion

    PubMed Central

    Heinemann, Lutz; Krinelke, Lars

    2012-01-01

    Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient. PMID:22920824

  2. Multiple Intravenous Infusions Phase 2b: Laboratory Study

    PubMed Central

    Pinkney, Sonia; Fan, Mark; Chan, Katherine; Koczmara, Christine; Colvin, Christopher; Sasangohar, Farzan; Masino, Caterina; Easty, Anthony; Trbovich, Patricia

    2014-01-01

    Background Administering multiple intravenous (IV) infusions to a single patient via infusion pump occurs routinely in health care, but there has been little empirical research examining the risks associated with this practice or ways to mitigate those risks. Objectives To identify the risks associated with multiple IV infusions and assess the impact of interventions on nurses’ ability to safely administer them. Data Sources and Review Methods Forty nurses completed infusion-related tasks in a simulated adult intensive care unit, with and without interventions (i.e., repeated-measures design). Results Errors were observed in completing common tasks associated with the administration of multiple IV infusions, including the following (all values from baseline, which was current practice): setting up and programming multiple primary continuous IV infusions (e.g., 11.7% programming errors) identifying IV infusions (e.g., 7.7% line-tracing errors) managing dead volume (e.g., 96.0% flush rate errors following IV syringe dose administration) setting up a secondary intermittent IV infusion (e.g., 11.3% secondary clamp errors) administering an IV pump bolus (e.g., 11.5% programming errors) Of 10 interventions tested, 6 (1 practice, 3 technology, and 2 educational) significantly decreased or even eliminated errors compared to baseline. Limitations The simulation of an adult intensive care unit at 1 hospital limited the ability to generalize results. The study results were representative of nurses who received training in the interventions but had little experience using them. The longitudinal effects of the interventions were not studied. Conclusions Administering and managing multiple IV infusions is a complex and risk-prone activity. However, when a patient requires multiple IV infusions, targeted interventions can reduce identified risks. A combination of standardized practice, technology improvements, and targeted education is required. PMID:26316919

  3. Multiple Intravenous Infusions Phase 2a: Ontario Survey

    PubMed Central

    Fan, Mark; Koczmara, Christine; Masino, Caterina; Cassano-Piché, Andrea; Trbovich, Patricia; Easty, Anthony

    2014-01-01

    Background Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. Objective To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. Data Sources and Review Methods Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). Results Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions administration of secondary infusions with/as high-alert continuous IV medications potential confusion about how IV tubing should be labelled to reflect replacement date and time interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units coadministration of continuous or intermittent infusions on central venous pressure monitoring ports variability in respondents’ awareness of the infusion pump's bolus capabilities Limitations Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. Conclusions The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID

  4. Avoiding Infusion Confusion Kindergarten through 3rd Grade. A Practical Handbook for Infusing Environmental Activities into Your Classroom.

    ERIC Educational Resources Information Center

    Hayden, Harvey; And Others

    To some educators, infusing environmental education into different subject areas at different levels may seem like an insurmountable task. This handbook was developed to take the guesswork out of this process and alleviate the fear and confusion that may result. It was designed to assist with infusing awareness and attitude activities into the…

  5. Avoiding Infusion Confusion 4th through 6th Grades. A Practical Handbook for Infusing Environmental Activities into Your Classroom.

    ERIC Educational Resources Information Center

    Hayden, Harvey; And Others

    To some educators, infusing environmental education into different subject areas at different levels may seem like an insurmountable task. This handbook was developed to take the guesswork out of this process and alleviate the fear and confusion that may result. It was designed to assist with infusing knowledge and attitude activities into the…

  6. Avoiding Infusion Confusion 7th through 9th Grades. A Practical Handbook for Infusing Environmental Activities into Your Classroom.

    ERIC Educational Resources Information Center

    Hayden, Harvey; And Others

    To some educators, infusing environmental education into different subject areas at different levels may seem like an insurmountable task. This handbook was developed to take the guesswork out of this process and alleviate the fear and confusion that may result. It was designed to assist with infusing knowledge, skill and attitude activities into…

  7. A CLINICAL TRIAL COMBINING DONOR BONE MARROW INFUSION AND HEART TRANSPLANTATION: INTERMEDIATE-TERM RESULTS

    PubMed Central

    Pham, Si M.; Rao, Abdul S.; Zeevi, Adriana; Kormos, Robert L.; McCurry, Kenneth R.; Hattler, Brack G.; Fung, John J.; Starzl, Thomas E.; Griffith, Bartley P.

    2010-01-01

    Background Donor chimerism (the presence of donor cells of bone marrow origin) is present for years after transplantation in recipients of solid organs. In lung recipients, chimerism is associated with a lower incidence of chronic rejection. To augment donor chimerism with the aim to enhance graft acceptance and to reduce immunosuppression, we initiated a trial combining infusion of donor bone marrow with heart transplantation. Reported herein are the intermediate-term results of this ongoing trial. Methods Between September 1993 and August 1998, 28 patients received concurrent heart transplantation and infusion of donor bone marrow at 3.0 × 108 cells/kg (study group). Twenty-four contemporaneous heart recipients who did not receive bone marrow served as controls. All patients received an immunosuppressive regimen consisting of tacrolimus and steroids. Results Patient survival was similar between the study and control groups (86% and 87% at 3 years, respectively). However, the proportion of patients free from grade 3A rejection was higher in the study group (64% at 6 months) than in the control group (40%; P = .03). The prevalence of coronary artery disease was similar between the two groups (freedom from disease at 3 years was 78% in study patients and 69% in controls). Similar proportions of study (18%) and control (15%) patients exhibited in vitro evidence of donor-specific hyporesponsiveness. Conclusions The infusion of donor bone marrow reduces the rate of acute rejection in heart recipients. Donor bone marrow may play an important role in strategies aiming to enhance the graft acceptance. PMID:10733755

  8. Stimulation of muscle protein synthesis by long-term insulin infusion in severely burned patients.

    PubMed Central

    Sakurai, Y; Aarsland, A; Herndon, D N; Chinkes, D L; Pierre, E; Nguyen, T T; Patterson, B W; Wolfe, R R

    1995-01-01

    OBJECTIVE: To determine if long-term (7 days) infusion of insulin can ameliorate altered protein kinetics in skeletal muscle of severely burned patients and to investigate the hypothesis that changes in protein kinetics during insulin infusion are associated with an increased rate of transmembrane amino acid transport from plasma into the intracellular free amino acid pool. SUMMARY BACKGROUND DATA: In critically ill patients, vigorous nutritional support alone may often fail to entirely curtail muscle catabolism; insulin stimulates muscle protein synthesis in normal volunteers. METHODS: Nine patients with severe burns were studied once during enteral feeding alone (control period), and once after 7 days of high-dose insulin. The order of treatment with insulin was randomized. Data were derived from a model based on a primed-continuous infusion of L-[15N]phenylalanine, sampling of blood from the femoral artery and vein, and biopsies of the vastus lateralis muscle. RESULTS: Net leg muscle protein balance was significantly (p < 0.05) negative during the control period. Exogenous insulin eliminated this negative balance by stimulating protein synthesis approximately 350% (p < 0.01). This was made possible in part by a sixfold increase in the inward transport of amino acids from blood (p < 0.01). There was also a significant increase in leg muscle protein breakdown. The new rates of synthesis, breakdown, and inward transport during insulin were in balance, such that there was no difference in the intracellular phenylalanine concentration from the control period. The fractional synthetic rate of protein in the wound was also stimulated by insulin by approximately 50%, but the response was variable and did not reach significance. CONCLUSIONS: Exogenous insulin may be useful in promoting muscle protein synthesis in severely catabolic patients. PMID:7677459

  9. Heterogeneous responses of human limbs to infused adrenergic agonists: a gravitational effect?

    NASA Technical Reports Server (NTRS)

    Pawelczyk, James A.; Levine, Benjamin D.

    2002-01-01

    Unlike quadrupeds, the legs of humans are regularly exposed to elevated pressures relative to the arms. We hypothesized that this "dependent hypertension" would be associated with altered adrenergic responsiveness. Isoproterenol (0.75-24 ng x 100 ml limb volume-1 x min-1) and phenylephrine (0.025-0.8 microg x 100 ml limb volume-1 x min-1) were infused incrementally in the brachial and femoral arteries of 12 normal volunteers; changes in limb blood flow were quantified by using strain-gauge plethysmography. Compared with the forearm, baseline calf vascular resistance was greater (38.8 +/- 2.5 vs. 26.9 +/- 2.0 mmHg x 100 ml x min x ml-1; P < 0.001) and maximal conductance was lower (46.1 +/- 11.9 vs. 59.4 +/- 13.4 ml x ml-1 x min-1 x mmHg-1; P < 0.03). Vascular conductance did not differ between the two limbs during isoproterenol infusions, whereas decreases in vascular conductance were greater in the calf than the forearm during phenylephrine infusions (P < 0.001). With responses normalized to maximal conductance, the half-maximal response for phenylephrine was significantly less for the calf than the forearm (P < 0.001), whereas the half-maximal response for isoproterenol did not differ between limbs. We conclude that alpha1- but not beta-adrenergic-receptor responsiveness in human limbs is nonuniform. The relatively greater response to alpha1-adrenergic-receptor stimulation in the calf may represent an adaptive mechanism that limits blood pooling and capillary filtration in the legs during standing.

  10. Constant infusion transpulmonary thermodilution for the assessment of cardiac output in exercising humans.

    PubMed

    Calbet, J A L; Mortensen, S P; Munch, G D W; Curtelin, D; Boushel, R

    2016-05-01

    To determine the accuracy and precision of constant infusion transpulmonary thermodilution cardiac output (CITT-Q) assessment during exercise in humans, using indocyanine green (ICG) dilution and bolus transpulmonary thermodilution (BTD) as reference methods, cardiac output (Q) was determined at rest and during incremental one- and two-legged pedaling on a cycle ergometer, and combined arm cranking with leg pedaling to exhaustion in 15 healthy men. Continuous infusions of iced saline in the femoral vein (n = 41) or simultaneously in the femoral and axillary (n = 66) veins with determination of temperature in the femoral artery were used for CITT-Q assessment. CITT-Q was linearly related to ICG-Q (r = 0.82, CITT-Q = 0.876 × ICG-Q + 3.638, P < 0.001; limits of agreement ranging from -1.43 to 3.07 L/min) and BTD-Q (r = 0.91, CITT-Q = 0.822 × BTD + 4.481 L/min, P < 0.001; limits of agreement ranging from -1.01 to 2.63 L/min). Compared with ICG-Q and BTD-Q, CITT-Q overestimated cardiac output by 1.6 L/min (≈ 10% of the mean ICG and BTD-Q values, P < 0.05). For Q between 20 and 28 L/min, we estimated an overestimation < 5%. The coefficient of variation of 23 repeated CITT-Q measurements was 6.0% (CI: 6.1-11.1%). In conclusion, cardiac output can be precisely and accurately determined with constant infusion transpulmonary thermodilution in exercising humans. PMID:25919489

  11. The analgesic efficacy of continuous presternal bupivacaine infusion through a single catheter after cardiac surgery

    PubMed Central

    Nasr, Dalia Abdelhamid; Abdelhamid, Hadeel Magdy; Mohsen, Mai; Aly, Ahmad Helmy

    2015-01-01

    Background: Median sternotomy, sternal spreading, and sternal wiring are the main causes of pain during the early recovery phase following cardiac surgery. Aim: This study was designed to evaluate the analgesic efficacy of continuous presternal bupivacaine infusion through a single catheter after parasternal block following cardiac surgery. Materials and Methods: The total of 40 patients (American Society of Anesthesiologist status II, III), 45–60 years old, undergoing coronary – artery bypass grafting were enrolled in this prospective, randomized, double-blind study. A presternal catheter was inserted with continuous infusion of 5 mL/h bupivacaine 0.25% (Group B) or normal saline (Group C) during the first 48 postoperative hrs. Primary outcomes were postoperative morphine requirements and pain scores, secondary outcomes were extubation time, postoperative respiratory parameters, incidence of wound infection, Intensive Care Unit (ICU) and hospital stay duration, and bupivacaine level in blood. Statistical Methods: Student's t-test was used to analyze the parametric data and Chi-square test for categorical variables. Results: During the postoperative 48 h, there was marked reduction in morphine requirements in Group B compared to Group C, (8.6 ± 0.94 mg vs. 18.83 ± 3.4 mg respectively, P = 0.2), lower postoperative pain scores, shorter extubation time (117 ± 10 min vs. 195 ± 19 min, respectively, P = 0.03), better respiratory parameters (PaO2/FiO2, PaCO2 and pH), with no incidence of wound infection, no differences in ICU or hospital stay duration. The plasma concentration of bupivacaine remained below the toxic threshold (at T24, 1.2 ug/ml ± 0.3 and T48 h 1.7 ± 0.3 ug/ml). Conclusion: Continuous presternal bupivacaine infusion has resulted in better postoperative analgesia, reduction in morphine requirements, shorter time to extubation, and better postoperative respiratory parameters than the control group. PMID:25566704

  12. Renal macro- and microcirculation autoregulatory capacity during early sepsis and norepinephrine infusion in rats

    PubMed Central

    2013-01-01

    Introduction The relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity. Methods Ventilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions. Results Positive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion. Conclusion In our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion. PMID:23849307

  13. Chronic ANG II infusion and reflex control of norepinephrine and corticosterone in conscious rabbits.

    PubMed

    Brooks, V L; Hatton, D C

    1997-02-01

    The hypothesis that long-term increases in angiotensin II (ANG II) produce pressure-independent resetting of baroreflex control of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis was tested in rabbits by determining the effect of chronic ANG II infusion on reflex relationships between mean arterial pressure (MAP) and plasma concentrations of norepinephrine (NE) and corticosterone (CS). After 2 wk, ANG II increased MAP from 61 +/- 1 to 99 +/- 2 mmHg (P < 0.05) without altering heart rate or plasma NE concentration, but increased CS from 9.8 +/- 1.3 to 29.5 +/- 13.7 ng/ml (P < 0.05). Heart rate, NE, and CS baroreflex curves were all reset to a higher pressure level (P < 0.05) after 24 h, 1 wk, and 2 wk of ANG II. Forty minutes after stopping ANG II on the same days, MAP decreased, and curves were shifted back toward control (P < 0.05), indicating that ANG II was required for the resetting. Two findings suggest that the resetting action ofANG II is distinct from the pressor effect. First, although stopping ANG II reversed the hypertension as it reversed the resetting, reversal of the hypertension instead by prolonged infusion of nitroprusside along with ANG II did not have the same effect. Second, NE and heart rate baroreflex curves returned toward preinfusion positions after stopping ANG II (P < 0.05), even when the hypertension was nearly maintained by phenylephrine infusion. In conclusion, chronic increases in ANG II may have a global baroreflex resetting effect by a mechanism that is in part independent of the hypertension. PMID:9124469

  14. [Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs.

    PubMed

    Martins, Luiz Cláudio; Sabha, Maricene; Paganelli, Maria Ondina; Coelho, Otávio Rizzi; Ferreira-Melo, Silvia Elaine; Moreira, Marcos Mello; Cavalho, Adriana Camargo de; Araujo, Sebastião; Moreno Junior, Heitor

    2010-01-15

    BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al. PMID:20084333

  15. Intra-arterial chemoradiation therapy with weekly low-dose cisplatin for squamous cell carcinoma of the maxillary sinus.

    PubMed

    Kaneko, T; Tada, Y; Maruya, S; Takeishi, E; Miura, K; Masubuchi, T; Fushimi, C; Hasegawa, H; Kamata, S

    2015-06-01

    A new intra-arterial chemoradiation regimen that involves infusing low-dose cisplatin in combination with definitive irradiation was used in 36 patients diagnosed with squamous cell carcinoma of the maxillary sinus. The safety and therapeutic efficacy of this regimen were reviewed retrospectively. An intra-arterial catheter was inserted in a retrograde manner into the target artery via the superficial temporal artery or occipital artery. Intra-arterial infusion was performed using cisplatin at a dose of 20-50mg/m(2) per week for 6-8 weeks. At the same time, sodium thiosulphate was infused as a neutralizing agent. Irradiation was performed at 60Gy in 30 fractions. All 36 patients completed treatment. Grade 3 adverse events occurred in only seven patients (19.4%) and no grade 4 events were noted. As a primary therapy, the complete response rate was 83.3%, the partial response rate was 16.7%, and the overall response rate was 100%. The 2-year local control rate was 63.0%, and the 2-year overall survival rate was 75.5%. The 2-year preservation rate of the hard palate was 97.1%, that of the eyeball was 97.2%, and that of visual function was 94.4%. This treatment regimen can contribute to improving the quality of life of patients without reducing the curability of the therapy. PMID:25843537

  16. False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion

    SciTech Connect

    Smits, P.; Corstens, F.H.; Aengevaeren, W.R.; Wackers, F.J.; Thien, T. )

    1991-08-01

    The vasodilator effect of intravenously administered dipyridamole may be caused by an increase in endogenous plasma adenosine levels. The authors evaluated the effect of caffeine, an adenosine receptor antagonist, on the diagnostic results of dipyridamole-201Tl myocardial imaging in eight patients with coronary artery disease. Caffeine infusion significantly attenuated the dipyridamole-induced fall in blood pressure and the accompanied increase in heart rate. The infusion of dipyridamole alone resulted in chest pain and ST-segment depressions on the electrocardiogram in four patients, whereas none of these problems occurred when the tests were repeated after caffeine. In six of eight patients, caffeine was responsible for false-negative dipyridamole-201Tl tests. Semiquantitive scores of the dipyridamole-induced 201Tl perfusion defects were decreased by caffeine from 9.0 {plus minus} 0.9 to 2.0 {plus minus} 1.1 points (p less than 0.05). Computerized analysis revealed a caffeine-mediated reduction in the percent reversibility of the images from 46% {plus minus} 16% to 6% {plus minus} 10% (p less than 0.05). They conclude that the use of caffeinated products prior to dipyridamole-201Tl testing may be responsible for false-negative findings.

  17. Thallium scintigraphy during dobutamine infusion: nonexercise-dependent screening test for coronary disease

    SciTech Connect

    Mason, J.R.; Palac, R.T.; Freeman, M.L.; Virupannavar, S.; Loeb, H.S.; Kaplan, E.; Gunnar, R.M.

    1984-03-01

    Exercise thallium scintigraphy has proven to be a sensitive method for detecting coronary artery disease (CAD). However, early redistribution of thallium and inadequate exercise can reduce its sensitivity. In this study, dobutamine was infused in incremental doses (5, 10, 15, and 20 micrograms/kg/min) in 24 patients being evaluated for chest pain. Thallium scintigraphy was completed during the maximum dose of dobutamine tolerated and repeated 4 hours later. Significant CAD was present in 16 patients; the remaining eight had normal coronaries. Exercise ECG was obtained in 23 patients. During dobutamine thallium scintigraphy, reversible perfusion defects occurred in 15 of 16 CAD and in one of eight non-CAD patients, resulting in a sensitivity of 94% and a specificity of 87%. Exercise ECG had a sensitivity of 60% and a specificity of 63%. We conclude that: (1) dobutamine thallium scintigraphy appears to be a sensitive method for detecting significant CAD and provided a more sensitive screening test than exercise ECG; (2) dobutamine thallium scintigraphy is especially useful in patients who cannot exercise; and (3) because imaging occurs during dobutamine infusion, the problem of early redistribution may be mitigated.

  18. Local cerebral glucose utilization in monkeys with hemiparkinsonism induced by intracarotid infusion of the neurotoxin MPTP.

    PubMed

    Palombo, E; Porrino, L J; Bankiewicz, K S; Crane, A M; Sokoloff, L; Kopin, I J

    1990-03-01

    Quantitative 2-[14C]deoxyglucose autoradiography was used to map the pattern of alterations in local cerebral glucose utilization associated with unilateral lesions of the substantia nigra pars compacta produced by the infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into one internal carotid artery of rhesus monkeys. These monkeys become hemiparkinsonian, displaying rigidity, bradykinesia, and tremor of the limbs contralateral to the side of MPTP infusion; during spontaneous activity they turn toward the side of the lesion. Eighty-two brain areas were examined, and statistically significant metabolic changes were confined mainly to basal ganglia structures ipsilateral to the side of the lesion. Glucose utilization was reduced in the substantia nigra pars compacta and ventral tegmental area, i.e., in the areas of cell loss. Increases in glucose utilization in regions normally innervated by the lesioned area were observed in the post-commissural portions of the putamen and dorsolateral caudate. Other structures showing statistically significant metabolic changes were the external segment of the globus pallidus (+40%), subthalamic nucleus (-17%), and pedunculopontine nucleus (+15%). There were also smaller changes in portions of the thalamus (ventral anterior nucleus, parafascicular nucleus) and premotor cortex. All significant metabolic changes were confined to the side of the substantia nigra lesion and were essentially restricted to regions involved in the production of movement or maintenance of posture. PMID:2319306

  19. Optimizing the Concentration and Bolus of a Drug Delivered by Continuous Infusion

    PubMed Central

    Thall, Peter F.; Szabo, Aniko; Nguyen, Hoang Q.; Amlie-Lefond, Catherine M.; Zaidat, Osama O.

    2011-01-01

    Summary We consider treatment regimes in which an agent is administered continuously at a specified concentration until either a response is achieved or a predetermined maximum infusion time is reached. Response is an event defined to characterize therapeutic efficacy. A portion of the maximum planned total amount administered is given as an initial bolus. For such regimes, the amount of the agent received by the patient depends on the time to response. An additional complication when response is evaluated periodically rather than continuously is that the response time is interval censored. We address the problem of designing a clinical trial in which such response time data and a binary indicator of toxicity are used together to jointly optimize the concentration and the size of the bolus. We propose a sequentially adaptive Bayesian design that chooses the optimal treatment for successive patients by maximizing the posterior mean utility of the joint efficacy-toxicity outcome. The methodology is illustrated by a trial in which tissue plasminogen activator is infused intra-arterially as rapid treatment for acute ischemic stroke. PMID:21401568

  20. On-line dialysate infusion to estimate absolute blood volume in dialysis patients.

    PubMed

    Schneditz, Daniel; Schilcher, Gernot; Ribitsch, Werner; Krisper, Peter; Haditsch, Bernd; Kron, Joachim

    2014-01-01

    It was the aim to measure the distribution volume and the elimination of ultra-pure dialysate in stable hemodialysis patients during on-line hemodiafiltration (HDF). Dialysate was automatically infused as a volume indicator using standard on-line HDF equipment. Indicator concentration was noninvasively measured in the arterial blood-line (using the blood volume monitor, Fresenius Medical Care, Bad Homburg vor der Höhe, Germany), and its time course was analyzed to obtain the elimination rate and the distribution volume V(t) at the time of dilution. Blood volume at treatment start (V0) was calculated accounting for the degree of intradialytic hemoconcentration. Five patients (two females) were studied during 15 treatments. Two to six measurements using indicator volumes ranging from 60 to 210 ml were done in each treatment. V0 was 4.59 ± 1.15 L and larger than the volume of 4.08 ± 0.48 L estimated from anthropometric relationships. The mean half-life of infused volume was 17.2 ± 29.7 min. Given predialysis volume expansion V0 was consistent with blood volume determined from anthropometric measurements. Information on blood volume could substantially improve volume management in hemodialysis patients and fluid therapy in intensive care patients undergoing extracorporeal blood treatment. The system has the potential for complete automation using proper control inputs for BVM and HDF modules of the dialysis machine. PMID:24814842

  1. Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

    PubMed Central

    de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.

    2015-01-01

    Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552

  2. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  3. Isolated limb infusion chemotherapy for melanoma: an overview of early experience at the Adelaide Melanoma Unit

    PubMed Central

    Giles, Mitchell H; Coventry, Brendon J

    2013-01-01

    Background Isolated limb infusion (ILI) using cytotoxic agents has been demonstrated to be an effective and less invasive alternative modality than isolated limb perfusion for the treatment of melanoma localized to a limb. Percutaneous catheters were inserted into the axial artery and vein of the affected limb while using a pneumatic cuff to restrict limb vascular flow proximally to “isolate” the limb from the body and enable delivery of high-dose intra-arterial chemotherapy selectively to the limb. The ILI technique was developed at the Sydney Melanoma Unit (now renamed the Melanoma Institute Australia), and only a few other centers have reported separate results. We report our early results using the ILI technique for management of locally recurrent surgically nonresectable melanoma. Methods and results Twenty-eight ILI procedures were performed in 20 patients treated with one or more procedures between 1997 and 2007. Patient parameters and clinical responses were evaluated. The median follow-up duration was 15.9 months after the first ILI, with an overall response rate after one or more infusions of 70%, of which 35% were complete responders and 35% were partial responders, with a further 20% showing stable disease, giving a “clinically significant” response rate of 90%. After one ILI (n = 20), the overall response rate was 70%, with 20% complete responders and 50% partial responders, and 20% with stable disease. Low limb toxicities were generally observed, and no amputations were required. Conclusion ILI chemotherapy is a useful technique, which can be readily repeated for control of melanoma in the limb. It is generally well tolerated, and is capable of achieving a cure, delayed progression, or effective palliation in selected cases. The longest survivors in this series were 8 and 10 years from the last ILI. PMID:23990731

  4. Needle infusion avoids using sutures and prevents hypotony in the 23 gauge sutureless vitrectomy

    PubMed Central

    Zhang, Yingjie; Zhu, Dongqing; Zhou, Jibo

    2015-01-01

    Objective: To investigate the effects of needle infusion on preventing wound leakage and hypotony in sutureless vitrectomy. Methods: We retrospectively reviewed 230 consecutive eyes of 23-gauge pars plana vitrectomy with or without needle infusion, and further measured the wound leakage and intraocular pressure (IOP) without using a suture. Results: In the eyes with primary needle infusion inserted before infusion cannula removal, IOP was stable during and after infusion cannula removal. No suture was needed in the procedure. Postoperative hypotony did not occurred in all eyes with needle infusion either. Conclusion: Needle infusion inserted before infusion cannula removal can avoid using sutures and prevent hypotony intraoperatively and postoperatively. PMID:26770552

  5. Pre-rigor infusion with kiwifruit juice improves lamb tenderness.

    PubMed

    Han, J; Morton, J D; Bekhit, A E D; Sedcole, J R

    2009-07-01

    The ability of pre-rigor infusion of kiwifruit juice to improve the tenderness of lamb was investigated. Lamb carcasses were infused (10% body weight) with fresh kiwifruit juice (Ac), water (W) and a non-infusion control (C) treatment. Infusion treatment had no effect on lamb hot carcass weight, cold carcass weight and chilling evaporative losses. The infused treatment carcasses of Ac and W had lower (P<0.05) pH values than C carcasses during the initial 12h post-mortem. The LD muscles from Ac carcasses were more tender with significantly lower shear force (P<0.001) compared with C and W carcasses during the six days following infusion with the kiwifruit juice. The enhanced proteolytic activity (P=0.002) resulting from the infused kiwifruit juice in Ac carcasses was associated with significant degradation of the myofibrillar proteins, appearance of new peptides and activation of m-calpain during post-mortem ageing. Thus, kiwifruit juice is powerful and easily prepared meat tenderizer, which could contribute efficiently and effectively to the meat tenderization process. PMID:20416722

  6. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism.

    PubMed

    Galindo, C; Larsen, M; Ouellet, D R; Maxin, G; Pellerin, D; Lapierre, H

    2015-11-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate (BHBA) in postpartum dairy cows according to a generalized randomized incomplete block design with repeated measures in time. At calving, cows were blocked according to parity (second and third or greater) and were allocated to 2 treatments: abomasal infusion of water (n=4) or abomasal infusion of free AA with casein profile (AA-CN; n=5) in addition to the same basal diet. The AA-CN infusion started with half the maximal dose at 1 d in milk (DIM) and then steadily decreased from 791 to 226 g/d from DIM 2 to 29 to cover the estimated essential AA deficit. On DIM 5, 15, and 29, D[6,6-(2)H2]-glucose (23.7 mmol/h) was infused into a jugular vein for 5h, and 6 blood samples were taken from arterial, portal, hepatic, and mammary sources at 45-min intervals, starting 1h after the initiation of the D[6,6-(2)H2]glucose infusion. Trans-organ fluxes were calculated as veno-arterial differences times plasma flow (splanchnic: downstream dilution of deacetylated para-aminohippurate; mammary: Fick principle using Phe+Tyr). Energy-corrected milk and lactose yields increased on average with AA-CN by 6.4 kg/d and 353 g/d, respectively, with no DIM × treatment interaction. Despite increased AA supply and increased demand for lactose secretion with AA-CN, net hepatic release of glucose remained unchanged, but WB-Ra of glucose tended to increase with AA-CN. Portal true flux of glucose increased with AA-CN and represented, on average, 17% of WB-Ra. Splanchnic true flux of glucose was unaltered by treatments and was numerically equivalent to WB-Ra, averaging 729 and 741 mmol/h, respectively. Mammary glucose utilization increased with AA-CN infusion, averaging 78% of WB-Ra, and increased

  7. Effects of cholic acid infusion in fetal lambs.

    PubMed

    Campos, G A; Guerra, F A; Israel, E J

    1986-01-01

    The effects of prolonged intravenous infusions of cholic acid into fetal lambs are described in this study. The ewes (n = 10, 11 fetuses) were operated on at 114 days of gestation (term = 150 days) by placing plastic catheters in maternal and fetal vessels and in the amniotic cavity. Gestational ages were confirmed after delivery by radiographic examination of the ossification centers of the fetal legs. Infusions of cholic acid (1.6 mumoles/min-1) started 8 to 10 days after surgery in 5 fetuses (including one twin). The remaining 6 fetuses (also including one twin) were infused with 5% dextrose in water. Total plasma bile acids at the beginning of the experiment were similar in both groups (23.8 +/- 6.6 vs. 24.3 +/- 5.7 microM). No significant changes in fetal heart rate, blood pressure, blood gases or pH were detected during the infusion. Meconium-stained amniotic fluid was observed during the third day of infusion in all the fetuses infused with cholic acid and in one control fetus. Fetuses infused with cholic acid were delivered alive 19-26 days before term. The concentration of plasma bile acids in the experimental group at delivery was 829 +/- 305 microM, i.e. significantly higher than that of the control group (24.4 +/- 5.7 microM). Control fetuses (except one twin) were delivered at term. We concluded that cholic acid, even at the high dose infused, is neither lethal nor severely harmful for the fetus. Meconium passage of the fetuses infused with cholic acid, in our experiment, appeared to be related to the stimulatory effect of cholic acid on fetal colonic motility rather than to fetal hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3716776

  8. Radiofrequency ablation during continuous saline infusion can extend ablation margins

    PubMed Central

    Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

    2013-01-01

    AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area. METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment. RESULTS: No liquid infusion was 17.3 ± 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 ± 3.3 mL) than with 5% glucose (21.4 ± 2.2 mL), 50% glucose (16.5 ± 0.9 mL) or no liquid infusion (17.3 ± 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose. CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence. PMID:23483097

  9. In vivo effects of urease-producing bacteria involved with the pathogenesis of infection-induced urolithiasis on renal urokinase and sialidase activity.

    PubMed

    du Toit, P J; van Aswegen, C H; Nel, J A; Steyn, P L; Ligthelm, A J; du Plessis, D J

    1995-01-01

    Many hypotheses have been proposed for renal stone formation. It has been argued that with infection-induced renal stones the hydrolysis of urea by bacterial urease increases urinary pH, with consequent stone formation. Unfortunately, this theory is not applicable to the micro-organisms that do not produce urease (e.g. Escherichia coli). It has been recently reported that E. coli reduces the urinary urokinase activity of male rats, but does not influence the urinary sialidase activity. This study has now been expanded to the urease-producing bacteria Proteus mirabilis, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa and Micrococcus luteus. Subcutaneous injections with these bacteria were found to significantly (P < 0.003) reduce the UK activity of extrarenally obstructed kidneys. The urease-producing mammalian skin bacterium, M. luteus, was, however, the exception (P = 0.1079). In contrast to S. epidermidis, P. aeruginosa and M. luteus (P < 0.0213), P. mirabilis and S. aureus had no effect on renal sialidase activity (P < 0.4047). These results may explain why Proteus species are predominant in infection-induced renal stones. According to the urokinase-sialidase hypothesis, a decrease in urinary urokinase activity should increase the uromucoid levels, whilst no effect on the urinary sialidase activity should favour conversion of urinary uromucoid to mineralizable matrix. These conditions may lead to renal stone formation. An increase in urinary pH resulting from urease-producing micro-organisms will increase salt precipitation on the uromucoid. It is thus concluded that urease-producing bacteria may play a double role in renal stone formation. PMID:8839391

  10. Single ketamine infusion and neurocognitive performance in bipolar depression.

    PubMed

    Permoda-Osip, A; Kisielewski, J; Bartkowska-Sniatkowska, A; Rybakowski, J K

    2015-03-01

    We estimated neurocognitive performance using the trail making test (TMT) and the Stroop color-word interference test before, and on the 3(rd) day after a single infusion of ketamine, in 18 bipolar depressed patients receiving mood-stabilizing drugs. The performance on all tests significantly improved on the 3(rd) day after ketamine infusion which correlated positively with baseline intensity of neuropsychological impairment and was not associated either with baseline intensity of depression or reduction of depressive symptoms after 3 or 7 days. The results suggest that in such population of patients, single ketamine infusion may improve neuropsychological performance independently of antidepressant effect. PMID:25347227

  11. [The development of multifunction intravenous infusion quantitative packaging device].

    PubMed

    Zhao, Shufang; Li, Ruihua; Shen, Lianhong

    2012-11-01

    Aimed at tackling the compatibility issues arising from the drug reaction in intravenous infusion tube, we developed a simple, suitable and multi-function intravenous infusion tube for the special use for rescuing critical patients, the elderly, children etc. Each drug in a transfusion process can be filtered to realize quantitative packet and packet delivery. Thus, the drugs in the infusion tube are prevented from meeting with each other. No overlap, no particle pollution occurred. Stable performance and accurate dosage are maintained. As a result safety is ensured during drug delivery. PMID:23461118

  12. Acid-Base Homeostasis: Overview for Infusion Nurses.

    PubMed

    Masco, Natalie A

    2016-01-01

    Acid-base homeostasis is essential to normal function of the human body. Even slight alterations can significantly alter physiologic processes at the tissue and cellular levels. To optimally care for patients, nurses must be able to recognize signs and symptoms that indicate deviations from normal. Nurses who provide infusions to patients-whether in acute care, home care, or infusion center settings-have a responsibility to be able to recognize the laboratory value changes that occur with the imbalance and appreciate the treatment options, including intravenous infusions. PMID:27598068

  13. Pain and Gaps in IT Infusion

    NASA Astrophysics Data System (ADS)

    Fatland, D. R.; van Ingen, C.; Beran, B.; Heavner, M.; Habermann, M.; Berner, L.

    2008-12-01

    The process of adopting a new information technology 'X' within geoscience research projects is hindered by two strong barriers: The pain associated with learning about, adopting and adapting to X, and corresponding gaps in the 'ease-of-adoption' process left by the builders of X. As builders and providers of two such X's we discuss several lessons learned from two distinct points along the data pipeline (data acquisition, storage, retrieval, archival, cleaning, provenance, browsing and analysis). We begin with work at Microsoft Research to generalize the CUAHSI Observations Data Model to a "next generation" Environmental Data Model (EDM) with the idea of supporting trans-disciplinary information across remote sensing, in situ, sample analysis, archival, and model data spaces. We then turn to an in situ sensor network microserver developed through NASA support for harsh environment data acquisition. The primary 'IT infusion' candidate research project here is SEAMONSTER, the Southeast Alaska Monitoring Network for Science, Telecommunications, Education and Research. We trace the adoption pathway, including gaps and pain, from deployment through to data registration on an EDM data catalog server. We discuss architecture, documentation and technical support in terms of an end-result success metric: How easily can this project's open data results be discovered and used?

  14. [Clinical experimental studies of postoperative infusion analgesia].

    PubMed

    Dick, W; Knoche, E; Grundlach, G; Klein, I

    1983-06-01

    30 postoperative patients, who had undergone abdominal gynaecological surgery with standard general anaesthesia were randomly divided into three groups and received, in the recovery ward, a continuous infusion of either pentazocine, piritramid, or ketamine. The patients rated their pain on a 15 cm pain analogue score. Group I pentazocine: Mean dosage on the day of operation 0.12 mg/kg/h, 0.1 mg/kg/h on the first and only 0.07 mg/kg/h on the second postoperative day. Pentazocine blood levels were on average 50 micrograms/l. Group II piritramid: Mean dosage on the day of operation 0.038 mg/kg/h, 0.024 mg/kg/h on the first and 0.019 mg/kg/h on the second postoperative day. Blood levels of piritramid were not determined because there is no satisfactory assay available. Group III ketamine: mean dosage on the day of operation 0.32 mg/kg/h, 0.28 mg/kg/h on the first and 0.29 mg/kg/h on the second postoperative day. Ketamine blood levels lay between 120 and 180 micrograms/l. The three analgesics did not cause any important haemodynamic or respiratory side effects. Pentazocine and piritramid were the most effective analgesics, ketamine was the least effective with a high incidence of side effects. PMID:6412586

  15. Clinical experimental studies of postoperative infusion analgesia.

    PubMed

    Knoche, E; Dick, W; Bowdler, I; Gundlach, G

    1983-01-01

    Thirty postoperative patients, after undergoing abdominal hysterectomy and standard general anesthesia, were randomly allocated to three groups and received, in the recovery ward, a continuous infusion of either pentazocine, piritramide, or ketamine. The patients rated their pain on a 15-cm visual analog scale. Patients in group 1 received pentazocine. Mean dosage was 0.12 mg/kg/hr on the day of operation, 0.1 mg/kg/hr on the first postoperative day, and only 0.07 mg/kg/hr on the second postoperative day. Pentazocine blood levels averaged 50 micrograms/L. Patients in group 2 received piritramide. Mean dosage was 0.038 mg/kg/hr on the day of operation, 0.024 mg/kg/hr on the first postoperative day, and 0.019 mg/kg/hr on the second postoperative day. Blood levels of piritramide were not determined because no satisfactory assay is available. Patients in group 3 received ketamine. Mean dosage was 0.32 mg/kg/hr on the day of operation, 0.28 mg/kg/hr on the first postoperative day, and 0.29 mg/kg/hr on the second postoperative day. Ketamine blood levels ranged between 120 and 180 micrograms/L. None of the three analgesics caused any important hemodynamic or respiratory side effects. Pentazocine and piritramide were more effective analgesics than ketamine was. Ketamine also had a higher incidence of side effects. PMID:6627285

  16. Drag reduction on liquid infused superhydrophobic surfaces

    NASA Astrophysics Data System (ADS)

    Kim, Jeong-Hyun; Rothstein, Jonathan

    2014-11-01

    The drag reduction on liquid infused superhydrophobic surfaces was measured through a microchannel. The microfluidic device consisted of two halves, a superhydrophobic surface and a microchannel, respectively. The superhydrophobic surface was created from a silicon wafer with ridge patterns 30 to 60 microns in width and spacing generated by a standard photolithography. A low viscosity, immiscible, incompressible silicone oil was filled to the gaps of the superhydrophobic surfaces. Several microchannels varying in size from 100 to 200 microns were fabricated from PDMS with an inlet, outlet and two pressure ports. After flow coating the superhydrophobic surface with a uniform film of oil, the two halves were aligned and clamped together and the pressure drop measured. A systematic study on drag reduction and slip length was performed by varying the viscosity ratio between the water and oil phase between 0 to 50. Several aqueous glycerin solutions with different viscosity were prepared. The slip length, pressure drop, and longevity of the oil phase were studied as a function of surface geometry, capillary number and the dispense volume. NSF CBET-1334962.

  17. The Variable Rate Intravenous Insulin Infusion Protocol.

    PubMed

    Collard, Benjamin; Sturgeon, Jonathan; Patel, Natasha; Asharia, Shabbar

    2014-01-01

    Insulin use among inpatients is high and associated with severe and regular medication errors. An initial baseline audit showed a wide variation in the prescription of intravenous insulin within the trust. These included variation in the choice of fluid prescribed, electrolyte levels not consistently checked, handwritten illegible prescriptions, and varying parameters set for adjustment of the prescription. A Variable Rate Intravenous Insulin Infusion protocol (VRIII)) was introduced to standardize intravenous insulin prescription throughout the trust by all members of the clinical team. We looked at and measured uptake and effects of the VRIII protocol in improving standardization of insulin prescription for inpatients on insulin at St George's NHS trust. The protocol was uploaded to the intranet to allow access 24 hours a day and the staff educated about it. The VRIII protocol was routinely used successfully throughout the trust. Any initial problems were addressed through education of clinical staff. The protocol has shown decreased prescribing and administrative errors, whilst demonstrating good glucose and electrolyte control. Use of a standardized protocol helps reduce medication errors and demonstrates good glycaemic control. Regular and continued education of clinical staff is necessary to maintain its efficacy. PMID:26734228

  18. Intraosseous infusions in the emergency department.

    PubMed

    Parrish, G A; Turkewitz, D; Skiendzielewski, J J

    1986-01-01

    For most emergency physicians and pediatricians, the frustrations encountered when obtaining intravenous access in infants involved in traumatic or medical emergencies are well known. Although it is rare that parenteral access is absolutely unobtainable in a pediatric patient, minutes and sometimes hours are often lost as futile attempts are made to cannulate a collapsed vein of such a patient. Many alternatives to such a crisis situation, including the intratracheal, intracardiac, and sublingual routes of administration, have been proposed and efficaciously used. Disadvantages to these alternatives, however, include the inability to administer volume-expanding colloids or crystalloids, and a relatively narrow spectrum of useful medications. One relatively safe, well-proven, and technically easy method for giving replacement fluids, blood products, and numerous resuscitative drugs is infusion by the intraosseous route. Although not recommended as a replacement for current modes of intravascular access, we feel it has definite utility in selected situations and warrants the awareness of emergency physicians. The value, historical aspects, technique, and complications of this procedure are discussed. PMID:3947434

  19. Continuous subcutaneous insulin infusion: practical issues

    PubMed Central

    Saboo, Banshi D.; Talaviya, Praful A.

    2012-01-01

    The growing number of individuals with diabetes mellitus has prompted new way of treating these patients, continuous subcutaneous insulin infusion (CSII) or insulin pump therapy is an increasingly form of intensive insulin therapy. An increasing number of individuals with diabetes mellitus individuals of all ages have started using insulin pump therapy. Not everyone is a good candidate for insulin pump therapy, and the clinician needs to be able to determine which patients are able to master the techniques required and to watch for the adverse reactions that may develop. Insulin pump increases quality of life of patient with diabetes mellitus with increasing satisfaction with treatment and decrease impact of diabetes mellitus. Manual errors by insulin pump users may lead to hypo or hyperglycemia, resulting into diabetic ketoacidosis (DKA) sometimes. Some of practical aspect is associated with insulin pump therapy such as selection of candidates, handling of pump and selection of site, and pump setting, henceforth this review is prepared to explore and solve the practical problems or issues associated with pump therapy. PMID:23565394

  20. Use of adenosine echocardiography for diagnosis of coronary artery disease

    SciTech Connect

    Zoghbi, W.A. )

    1991-07-01

    Two-dimensional echocardiography combined with exercise is sensitive and specific in the detection of coronary artery disease (CAD) by demonstrating transient abnormalities in wall motion. Frequently, however, patients cannot achieve maximal exercise because of various factors. Pharmacologic stress testing with intravenous adenosine was evaluated as a means of detecting CAD in a noninvasive manner. Patients with suspected CAD underwent echocardiographic imaging and simultaneous thallium 201 single-photon emission computed tomography during the intravenous administration of 140 micrograms/kg/min of adenosine. An increase in heart rate, decrease in blood pressure, and increase in double product were observed during adenosine administration. Initial observations revealed that wall motion abnormalities were induced by adenosine in areas of perfusion defects. The adenosine infusion was well tolerated, and symptoms disappeared within 1 to 2 minutes after termination of the infusion. Therefore preliminary observations suggest that adenosine echocardiography appears to be useful in the assessment of CAD.

  1. Serum Soluble Urokinase-Type Plasminogen Activator Receptor Levels and Idiopathic FSGS in Children: A Single-Center Report

    PubMed Central

    Price, Heather E.; Gallon, Lorenzo; Langman, Craig B.

    2013-01-01

    Summary Background and objectives FSGS is the primary cause of childhood nephrotic syndrome leading to ESRD. Permeability factors, including circulating serum soluble urokinase-type plasminogen activator receptor (suPAR), have been postulated as putative causes in adults with primary FSGS. Similar results have yet to be proven in children. Design, setting, participants, & measurements This cross-sectional single-center study assessed the association of serum suPAR in children with FSGS or other glomerular and nonglomerular kidney diseases. Results This study examined 110 samples retrieved from 99 individuals (between January 2011 and April 2012), aged 1–21 years; of these individuals, 20 had primary FSGS, 24 had non-FSGS glomerular disease, 26 had nonglomerular kidney disease, and 29 were healthy controls. suPAR levels were not significantly different in children with FSGS, non-FSGS glomerular disease, and healthy controls (P>0.05). However, suPAR levels (median [25%–75%]) were higher in children with nonglomerular kidney disease (3385 pg/ml [2695–4392]) versus FSGS (2487 pg/ml [2191–3351]; P<0.05). Female patients with nephrotic-range proteinuria (U-Pr/Cr >2) had lower suPAR levels than those without proteinuria (2380 pg/ml [2116–2571] versus 3125 pg/ml [2516–4198], respectively; P<0.001). This trend was not seen among male participants; suPAR levels in all female participants were lower than in male participants (P=0.03). Thirty-four patients studied were kidney transplant recipients; transplant status was not associated with suPAR levels in patients with FSGS or non-FSGS diagnoses, independent of proteinuria, race, or sex (P>0.05). Conclusions On the basis of these results, circulating suPAR is unlikely the leading cause for childhood idiopathic FSGS. PMID:23620441

  2. Cytokines induce urokinase-dependent adhesion of human myeloid cells. A regulatory role for plasminogen activator inhibitors.

    PubMed Central

    Waltz, D A; Sailor, L Z; Chapman, H A

    1993-01-01

    Differentiation of monocytic precursors often results in adhesive properties thought to be important in migration. In this study, the influence of cytokines, known to induce macrophage differentiation, on the adhesiveness of the monocytic cell line U937 was examined in vitro. Despite development of a macrophage morphology, < 5% of cytokine-stimulated U937 cells were adherent at 24 h. Addition of 1-10 nM urokinase-type plasminogen activator (uPA) induced adherence in the presence of transforming growth factor type beta-1, 1,25-(OH)2 vitamin D3, granulocyte macrophage colony-stimulating factor, or tumor necrosis factor alpha. uPA-dependent adhesiveness was reversible after 24 h of stimulation with cytokines and uPA as adherence was prevented by the subsequent addition of anti-uPA antibodies. Adherence induced by diisopropylfluorophosphate-inactivated uPA was severalfold greater than that seen with active uPA. This difference was largely due to cell-surface turnover of active uPA complexed with plasminogen activator inhibitor (PAI). These data indicate that cytokines prime monocyte progenitors for uPA receptor-mediated signals leading to adherence, continued uPA receptor occupancy is required for adherence, and PAI decreases adherence by promoting clearance of uPA/PAI complexes. Thus the interaction of uPA and PAI at the cell surface, known to affect extracellular matrix proteolysis and hence myeloid cell migration, also regulates adhesion. The coordinated regulation of these two uPA functions by PAI may enhance the migratory potential of monocytic cells. Images PMID:8386190

  3. Thrombosis recanalization by paeoniflorin through the upregulation of urokinase-type plasminogen activator via the MAPK signaling pathway

    PubMed Central

    YE, SONGSHAN; MAO, BINGYU; YANG, LEI; FU, WEIYUN; HOU, JUNRAN

    2016-01-01

    Paeoniflorin, the major component of Paeonia lactiflora pall, has previously been reported to prevent thrombosis. Plasminogen activator urokinase (uPA) is a serine protease that markedly facilitates normal thrombosis resolution. Paeoniflorin and uPA have been linked to the mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, the influence of paeoniflorin on the expression of uPA was investigated and the underlying regulatory mechanism was preliminarily determined. The prothrombotic state of the model animals treated with paeoniflorin were assessed by enzyme-linked immunosorbent assay (ELISA). Additionally, the cytotoxicity of paeoniflorin on human umbilical vein endothelial cell (HUVEC) cultures was estimated using a methyl thiazolyl tetrazolium assay and the possible pathways involved in the interaction between paeoniflorin and uPA were evaluated using western blot analysis. The ELISA results demonstrated that the levels of 6-keto prostaglandin F1a, fibronectin and uPA were significantly upregulated by treatment with paeoniflorin compared with control (P<0.05). By contrast, the expression of fibrinogen, D-dimer and thromboxane B2 were inhibited. With an increase in the concentration of paeoniflorin the cell viability of HUVECs decreased gradually. The results of western blot analysis demonstrated that paeoniflorin increased the phosphorylation of MAPK 14 (p38) and MAPK 8 (JNK). The present study demonstrated that paeoniflorin has the potential to improve the prethrombotic state and recanalize thrombosis by increasing the expression of uPA, which may be mediated via regulation of the p38 and JNK MAPK signaling pathways. However, this treatment effect was dependent on the concentration of paeoniflorin used, an unsuitable concentration of the agent would result in a negative effect on the anti-thrombosis pathways. PMID:27082639

  4. Overexpression of urokinase receptor increases matrix invasion without altering cell migration in a human osteosarcoma cell line.

    PubMed

    Karikó, K; Kuo, A; Boyd, D; Okada, S S; Cines, D B; Barnathan, E S

    1993-07-01

    Proteolysis triggered by receptor-bound urokinase-type plasminogen activator (uPA) involves a cascade of species-specific molecular interactions. To study the role of the uPA receptor (uPAR) in such interactions, a human osteosarcoma cell line (HOS), which normally expresses low levels of uPAR, was transfected with human uPAR complementary DNA. One of several stably transformed clonal cells lines, designated 2A2, was characterized and compared to the parental HOS, revealing the following: (a) stable incorporation of uPAR complementary DNA into the genome demonstrated by Southern blot analysis; (b) a 10-fold increase in steady state mRNA levels of uPAR assessed by Northern blot analysis; (c) a 2-fold increase in the surface expression of glycosylphosphatidylinositol anchored uPAR protein determined by enzyme-linked immunosorbent assay and by the specific binding of radiolabeled single chain uPA; (d) a 2-fold increase in internalization and degradation of radiolabeled uPA/PAI-1 complexes; and (e) a 2-fold increase in receptor-bound uPA-mediated plasmin generation measured by the cleavage of a chromogenic substrate and degradation of 125I-labeled laminin. The involvement of uPAR in cellular processes was determined by comparing 2A2 and HOS cells in in vitro migration and invasion assays. The migration of 2A2 cells were slower on fibronectin-coated surfaces in a linear under-agarose assay, but both cell lines migrated at the same rate on uncoated polycarbonate filters in Boyden chamber assays. In the invasion experiments, 4 times more 2A2 than HOS cells penetrated through the barrier of reconstituted basement membrane Matrigel. These data suggest that uPAR does not potentiate random cell migration but facilitates matrix degradation and subsequent cell invasion. PMID:8391387

  5. Cigarette Smoke and the Induction of Urokinase Plasminogen Activator Receptor In Vivo: Selective Contribution of Isoforms to Bronchial Epithelial Phenotype.

    PubMed

    Portelli, Michael A; Stewart, Ceri E; Hall, Ian P; Brightling, Christopher E; Sayers, Ian

    2015-08-01

    The urokinase plasminogen activator receptor (uPAR) gene (PLAUR) has been identified as an asthma susceptibility gene, with polymorphisms within that gene being associated with baseline lung function, lung function decline, and lung function in a smoking population. Soluble cleaved uPAR (scuPAR), a molecule identified as a marker of increased morbidity and mortality in a number of diseases, has been shown to be elevated in the airways of patients with asthma and in patients with chronic obstructive pulmonary disease. However, the functionality of soluble receptor isoforms and their relationship with an important initiator for obstructive lung disease, cigarette smoke, remains undefined. In this study, we set out to determine the effect of cigarette smoke on soluble uPAR isoforms, its regulatory pathway and the resultant effect on bronchial epithelial cell function. We identified a positive association between cigarette pack-years and uPAR expression in the airway bronchial epithelium of biopsies from patients with asthma (n = 27; P = 0.0485). In vitro, cigarette smoke promoted cleavage of uPAR from the surface of bronchial epithelial cells (1.5× induction; P < 0.0001) and induced the soluble spliced isoform through changes in messenger RNA expression (∼2× change; P < 0.001), driven by loss of endogenous 3' untranslated region suppression. Elevated expression of the soluble isoforms resulted in a proremodeling cell phenotype, characterized by increased proliferation and matrix metalloproteinase-9 expression in primary bronchial epithelial cells. This suggests that cigarette smoke elevates soluble receptor isoforms in bronchial epithelial cells through direct (cleavage) and indirect (messenger RNA expression) means. These findings provide further insight into how cigarette smoke may influence changes in the airways of importance to airway remodeling and obstructive lung disease progression. PMID:25490122

  6. Prognostic relevance of urokinase plasminogen activator detection in micrometastatic cells in the bone marrow of patients with primary breast cancer.

    PubMed Central

    Solomayer, E. F.; Diel, I. J.; Wallwiener, D.; Bode, S.; Meyberg, G.; Sillem, M.; Gollan, C.; Kramer, M. D.; Krainick, U.; Bastert, G.

    1997-01-01

    Patients with an elevated level of urokinase plasminogen activator (uPA) in breast cancer tissue have an adverse prognosis. This study evaluated the prognostic relevance of uPA detection in disseminated tumour cells in bone marrow. Bone marrow was sampled intraoperatively from both iliac crests in 280 patients with primary breast cancer. Interphase cells were enhanced and stained immunocytologically with two antibodies: 2E11, which detects TAG 12--a tumour-associated glycoprotein typically expressed by almost all breast cancer cells--and the anti-uPA antibody HD-UK9. Thirty-five of the 2E11-positive women (n = 132, 47%) developed metastatic disease (median follow-up time 44 months). Of these, most were uPA positive (n = 23, 65%) and only 12 were uPA negative. Patients with uPA-positive cells in bone marrow (n = 98, 35%) had a significantly shorter metastasis-free interval (36 months) than women who were uPA negative (44.5 months). The worst prognosis was seen in patients positive for both markers (29.5 months), followed by those who were uPA negative and 2E11 positive (37 months). The detection of uPA on disseminated tumour cells characterizes a subgroup of patients with an even worse prognosis, who should undergo more aggressive adjuvant systemic therapy. For the first time, it was possible to evaluate an important qualitative parameter involved in the process of breast cancer metastases. Images Figure 1 PMID:9310251

  7. CFTR suppresses tumor progression through miR-193b targeting urokinase plasminogen activator (uPA) in prostate cancer.

    PubMed

    Xie, C; Jiang, X H; Zhang, J T; Sun, T T; Dong, J D; Sanders, A J; Diao, R Y; Wang, Y; Fok, K L; Tsang, L L; Yu, M K; Zhang, X H; Chung, Y W; Ye, L; Zhao, M Y; Guo, J H; Xiao, Z J; Lan, H Y; Ng, C F; Lau, K M; Cai, Z M; Jiang, W G; Chan, H C

    2013-05-01

    Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development. PMID:22797075

  8. Peripheral artery disease - legs

    MedlinePlus

    ... if they have a history of: Abnormal cholesterol Diabetes Heart disease (coronary artery disease) High blood pressure ( hypertension ) Kidney disease involving hemodialysis Smoking Stroke ( cerebrovascular disease )

  9. Necessity and risks of arterial blood sampling in healthy volunteer studies.

    PubMed

    Oertel, Bruno Georg; Vermehren, Johannes; Zimmermann, Michael; Huynh, Thomas Tao; Doehring, Alexandra; Ferreiros, Nerea; Senzel, Stephan; Schmitz-Rixen, Thomas; Erbe, Matthias; Geisslinger, Gerd; Harder, Sebastian; Angst, Martin S; Lötsch, Jörn

    2012-10-01

    Arterial blood sampling is necessary when drugs such as the fast-acting opioid analgesic remifentanil exhibit relevant differences between arterial and venous blood concentrations. Arterial cannulation is generally considered to be clinically safe and has thus become a standard procedure in pharmacokinetic-pharmacodynamic assessments. However, rare cases of arterial occlusions have to be considered in risk-benefit assessments of arterial sampling in pharmacokinetic studies, especially when including healthy volunteers. In an actual case, arterial occlusion requiring surgical repair was caused by a factor V Leiden thrombophilia associated genetic variant F5 1691G>A (rs6025) and aggravated by a hypoplastic radial artery. Neither risk factor had been identified prior to enrolment by routine laboratory tests such as the prothrombin time (international normalized ratio), partial thromboplastin time and the clinical Allen's test of arterial function. Re-assessment of the necessity of arterial sampling showed that none of the potential alternatives, target concentrations of computerized infusions or venous concentrations during non-steady-state and steady-state conditions could provide the arterial concentrations. Relying on venous concentrations may result in erroneous pharmacodynamic parameters. Accurate pharmacokinetic-pharmacodynamic studies relying on precisely measured blood concentrations require serial sampling techniques during both steady-state and non-steady-state conditions. However, as illustrated by the presented case, incidents involving the generally safe procedure of arterial sampling are possible, although rare. To further minimize the risks, screening of subjects for prothrombotic risks and careful assessment of the suitability of the artery should be considered in pharmacokinetic studies requiring arterial cannulation. PMID:23018527

  10. Infusing Personal Responsibility into the Curriculum and Cocurriculum: Campus Examples

    ERIC Educational Resources Information Center

    O'Neill, Nancy

    2013-01-01

    This chapter highlights good practices and lessons learned for infusing personal responsibility--striving for excellence, cultivating academic integrity, and developing competence in ethical and moral reasoning and action--as outcomes of college.

  11. The selection and infusion of autonomy for Mars rovers

    NASA Technical Reports Server (NTRS)

    Woerner, D. F.

    2002-01-01

    This paper describes the process MSL in using to infuse autonomy into a rover, and describes attributes, and evaluation criteria and their use pertinent to autonomy technologies for Mars rovers in general.

  12. The Infusion of Multicultural Teaching in the Classroom.

    ERIC Educational Resources Information Center

    Yao, Esther Lee

    1984-01-01

    Multicultural education can be infused into the existing curriculum to help students become less ethnocentric and more cosmopolitan. Multicultural lessons dealing with numerals, abacus, calendars, and money exchange that were implemented successfully into a mathematics unit are discussed. (DF)

  13. Robust liquid-infused surfaces through patterned wettability

    NASA Astrophysics Data System (ADS)

    Wexer, Jason; Grosskopf, Abigail; Chow, Melissa; Fan, Yuyang; Jacobi, Ian; Stone, Howard

    2015-11-01

    Liquid-infused surfaces display advantageous properties that are normally associated with conventional gas-cushioned superhydrophobic surfaces. However, the surfaces can lose their novel properties if the infused liquid drains from the surface. We explore how drainage due to gravity or due to an external flow can be prevented through the use of chemical patterning. A small area of the overall surface is chemically treated to be preferentially wetted by the external fluid rather than the infused liquid. These sacrificial regions disrupt the continuity of the infused liquid, thereby preventing the liquid from draining from the texture. If the regions are patterned with the correct periodicity, drainage can be prevented entirely. The chemical patterns are created using spray-coating or deep-UV exposure, two economical techniques that are scalable to generate large-scale failure-resistant surfaces.

  14. Robust liquid-infused surfaces through patterned wettability.

    PubMed

    Wexler, Jason S; Grosskopf, Abigail; Chow, Melissa; Fan, Yuyang; Jacobi, Ian; Stone, Howard A

    2015-07-01

    Liquid-infused surfaces display advantageous properties that are normally associated with conventional gas-cushioned superhydrophobic surfaces. However, the surfaces can lose their novel properties if the infused liquid drains from the surface. We explore how drainage due to gravity or due to an external flow can be prevented through the use of chemical patterning. A small area of the overall surface is chemically treated to be preferentially wetted by the external fluid rather than the infused liquid. These sacrificial regions disrupt the continuity of the infused liquid, thereby preventing the liquid from draining from the texture. If the regions are patterned with the correct periodicity, drainage can be prevented entirely. The chemical patterns are created using spray-coating or deep-UV exposure, two facile techniques that are scalable to generate large-scale failure-resistant surfaces. PMID:26014378

  15. Infusing Social Responsibility into the Curriculum and Cocurriculum: Campus Examples

    ERIC Educational Resources Information Center

    Reason, Robert D.

    2013-01-01

    This chapter highlights good practices and lessons learned for infusing social responsibility--contributing to the larger community and taking seriously the perspectives of others--as outcomes of college.

  16. Metabolic and antioxidant profiles of herbal infusions and decoctions.

    PubMed

    Fotakis, Charalambos; Tsigrimani, Diamantina; Tsiaka, Thalia; Lantzouraki, Dimitra Z; Strati, Irini F; Makris, Constantinos; Tagkouli, Dimitra; Proestos, Charalampos; Sinanoglou, Vassilia J; Zoumpoulakis, Panagiotis

    2016-11-15

    This study implements NMR metabolomics and spectrophotometric studies (Folin-Ciocalteu, FRAP, ABTS) to infusions and decoctions of ten plant species in order to assess and compare the metabolic and antioxidant profiles for each botanical family. Multivariate and univariate data analyses highlighted the differences among the samples and pinpointed specific classes of compounds for each plant species as well as infusions and decoctions. The identified phenolic compounds by NMR, as well as the antioxidant profile, framed a trend of increased values in infusions compared to the decoctions. Moreover, the infusion procedure positively affected the extractability of the phenolic compounds compared to decoctions. The highest total phenolic content was found in Mentha spicata, while the lowest in Matricaria chamomilla preparations, irrespective of the preparation method. The preparation time for the decoctions was examined showing that the 15min preparations were generally found richer in phenolics and of higher antioxidant capacity. PMID:27283718

  17. COMPENSATORY CHANGES IN THE HIPPOCAMPUS FOLLOWING INTRADENTATE INFUSION OF COLCHICINE

    EPA Science Inventory

    Direct infusion of colchicine into the dentate gyrus of the hippocampus kills granule cells and elicits compensatory behavioral, neurochemical and neuroanatomical changes. olchicine-treated rats are less sensitive to the behavioral effects of cholinergic muscarinic receptor antag...

  18. Infusing Multicultural Counseling Competencies into Counselor Training Curriculum.

    ERIC Educational Resources Information Center

    Hays, Danica G.

    Multicultural counseling competencies have become an increasingly important component of counselor training. This article presents rationale for infusing multicultural competencies into select CACREP course areas, which are assessment, helping relationships, professional identity, and career development. Concrete activities that encompass proposed…

  19. Shear-Driven Failure of Liquid-Infused Surfaces

    NASA Astrophysics Data System (ADS)

    Wexler, Jason S.; Jacobi, Ian; Stone, Howard A.

    2015-04-01

    Rough or patterned surfaces infused with a lubricating liquid display many of the same useful properties as conventional gas-cushioned superhydrophobic surfaces. However, liquid-infused surfaces exhibit a new failure mode: the infused liquid film may drain due to an external shear flow, causing the surface to lose its advantageous properties. We examine shear-driven drainage of liquid-infused surfaces with the goal of understanding and thereby mitigating this failure mode. On patterned surfaces exposed to a known shear stress, we find that a finite length of the surface remains wetted indefinitely, despite the fact that no physical barriers prevent drainage. We develop an analytical model to explain our experimental results, and find that the steady-state retention results from the ability of patterned surfaces to wick wetting liquids, and is thus analogous to capillary rise. We establish the geometric surface parameters governing fluid retention and show how these parameters can describe even random substrate patterns.

  20. [Brain edema treatment procedure using continuous controlled infusion of mannitol in neurosurgical patients].

    PubMed

    Taranova, I I; Kokhno, V N

    2010-01-01

    The paper evaluates the efficiency and safety of the developed osmotherapy protocol using controlled continuous infusion of 15% mannitol solution. Two hundred and nine patients with intracranial hypertension (ICH) syndrome of various etiologies had 15% mannitol infusion, the rate of which was determined by clinical criteria. The infusion rate was 50 ml/hr with midline brain structure dislocation of 8 mm or more and major depression of consciousness (a Glasgow coma scale (GCS) score of less than 8) and 25 ml/hr with brain dislocation of 7-mm or less and a GCS score of 8 or higher. The monitoring program was as follows: Block 1 comprised the clinical and instrumental data characterizing the adequacy of brain perfusion (GCS, the magnitude of focal neurological symptoms, ICH, mean blood pressure, computed tomographic dislocation); Block 2 involved the clinical and laboratory data identifying the extracerebral complications of osmotherapy (packed cell volume, plasma osmolarity, urine density, and renal ultrasonography); Block 3 consisted of cerebral oximetry (CO) and Neurotrend. The authors' early proposed integral indicators of OC, such as interhemispheric asymmetry coefficient and hemodynamic conformity index, were used to estimate the adequacy of brain perfusion. In cerebral vasospasm, a Neurotrend microsensor was implanted at 3-cm depth for the direct quantitative determination of pO2, pCO2, pH, and brain temperature. ICH was characterized by natural changes in the CO indicators. In vasospasm, the mean linear blood flow velocity was 245 +/- 14 cm/sec in the basilar arteries, which was attended by low pO2 and metabolic acidosis, as shown by readings. Optimization of artificial ventilation, stabilization of hemodynamics, and the use of postural exposures and osmo diuretics promoted ICH normalization and central perfusion pressure optimization, which was accompanied by the disappearance of tissue hypoxia and acidosis, as suggested by Neurotrend reading. The duration of