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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. Hepatic Artery Infusion Chemotherapy

    PubMed Central

    Schüller, J.; Kroiss, A.; Dinstl, K.

    1990-01-01

    Hepatic artery chemotherapy was given to 36 patients, using totally implantable devices consisting of a port and external pump. Twenty-seven patients had inoperable liver metastases of colorectal origin. The infusion system was inserted by laparotomy into the hepatic artery via the gastroduodenal artery. There was no operative mortality. Thirteen infusion systems could not be used for chemotherapy due to dislodgement, early death and lack of follow-up. FUdR was infused every two weeks. There were minor local complications like thrombosis of the system and dislodgement of the port. Toxic effects could be managed by reducing the dose. Response to chemotherapy was evaluated by survival, clinical condition, CEA, ultrasound and CT six months after onset of arterial chemotherapy. Ten/twenty-three patients (43%) responded to therapy, eight of them died on the average 19 months after initial chemotherapy. Six patients were non-responders, seven had stable disease. Five/ten patients developed extrahepatic metastases. Mean survival time was 13.1 months, mean interval until relapse 10.6 months. PMID:2149279

  3. [Distribution of recombinant pro-urokinase in the rabbit blocked carotid artery].

    PubMed

    Matveev, M Iu; Mukhina, S A; Golubykh, V L; Domogatskiĭ, S P

    1999-07-01

    Distribution of recombinant pro-urokinase (PRU) in segments of blocked carotid arteries of rabbits was measured in 10, 20 and 30 minutes after i.v. administration of the RPU. Concentration of the latter in the bloodstream taken as 100% on the 3rd minute, after the infusion decreased to 42% in 10 min., 24% in 20 min., and 13% in 30 min. The RPU concentration decreased to 2% at the artery clamp point, to 20% at 10-15 cm from the clamp point, and remained constant for 10-30 min. A thrombolytic agent accumulated at the dead-end of the blocked artery, was not subject to rapid clearance in contrast to circulating pro-urokinase.

  4. 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.

  5. Anterograde Intra-Arterial Urokinase Injection for Salvaging Fibular Free Flap

    PubMed Central

    Lee, Dae-Sung; Jung, Sun-Il; Kim, Deok-Woo

    2013-01-01

    We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis. PMID:23730603

  6. Anterograde intra-arterial urokinase injection for salvaging fibular free flap.

    PubMed

    Lee, Dae-Sung; Jung, Sun-Il; Kim, Deok-Woo; Dhong, Eun-Sang

    2013-05-01

    We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis.

  7. [The fibrinolytic treatment with urokinase of acute arterial thrombosis].

    PubMed

    Ballester, A; Donato di Paola, M; Saccà, A; Cappello, I; D'Addato, M

    1993-01-01

    We present our experiences on 86 patients with acute arterial thrombosis of the legs, undergoing a fibrinolytic treatment with urokinase. Results from the treatment are analyzed according to: the administration way (systemic, locoregional, intrathrombotic), the level of thrombosis (upper or lower legs), the associated morbidity and mortality.

  8. 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

  9. The use of a volumetric infusion pump for the intra-arterial infusion of drugs.

    PubMed

    Cooper, A M; Lilliman, M

    1985-01-01

    Volumetric infusion pumps are widely used for intravenous infusions. We have extended their use to the intra-arterial infusion of drugs. An in vitro evaluation of the performance of such devices, under experimental conditions comparable to an intra-arterial infusion, was carried out. The results obtained confirmed the accuracy of volumetric infusion pumps for intra-arterial infusions. The system was found to be safe, reliable and simple in clinical practice.

  10. Intra-arterial urokinase for treatment of retrograde thrombosis following resection of an arteriovenous malformation. Case report.

    PubMed

    Sipos, E P; Kirsch, J R; Nauta, H J; Debrun, G; Ulatowski, J A; Bell, W R

    1992-06-01

    Retrograde thrombosis of feeding arteries is a potentially catastrophic complication occasionally reported following resection of arteriovenous malformations (AVM's). No successful therapy for this condition, which causes postoperative stroke, has previously been reported. A case of retrograde thrombosis of the left middle cerebral artery immediately following resection of a parietal AVM is reported in a patient with a retained intra-arterial catheter from preoperative embolization. The administration of urokinase within 4 hours of surgery resulted in dramatic clinical and angiographic improvement without hemorrhagic complications. While urokinase is considered highly experimental in this setting, this case demonstrates that thrombolytic agents should be viewed as therapeutic options worthy of further investigation.

  11. Combined Low-Frequency Ultrasound and Urokinase-Containing Microbubbles in Treatment of Femoral Artery Thrombosis in a Rabbit Model

    PubMed Central

    Mu, Yuming

    2016-01-01

    This paper aims to study the thrombolytic effect of low-frequency ultrasound combined with targeted urokinase-containing microbubble contrast agents on treatment of thrombosis in rabbit femoral artery; and to determine the optimal combination of parameters for achieving thrombolysis in this model. A biotinylated-avidin method was used to prepare microbubble contrast agents carrying urokinase and Arg-Gly-Asp-Ser (RGDS) peptides. Following femoral artery thrombosis in New Zealand white rabbits, microbubble contrast agents were injected intravenously, and ultrasonic exposure was applied. A 3 × 2 × 2 factorial table was applied to categorize the experimental animals based on different levels of combination of ultrasonic frequencies (Factor A: 1.6 MHz, 2.2 MHz, 2.8 MHz), doses of urokinase (Factor B: 90,000 IU/Kg, 180,000 IU/Kg) and ultrasound exposure time (Factor C: 30 min, 60 min). A total of 72 experimental animals were randomly divided into 12 groups (n = 6/group). Doppler techniques were used to assess blood flow in the distal end of the thrombotic femoral artery during the 120 minutes thrombolysis experiment. The rate of recanalization following thrombolysis was calculated, and thrombolytic efficacy was evaluated and compared. The thrombolytic recanalization rate for all experimental subjects after thrombolytic therapy was 68.1%. The optimal parameters for thrombolysis were determined to be 1) an ultrasound frequency of 2.2 MHz and 2) a 90,000 IU/kg dose of urokinase. Ultrasound exposure time (30 min vs. 60 min) had no significant effect on the thrombolytic effects. The combination of local low-frequency ultrasound radiation, targeted microbubbles, and thrombolytic urokinase induced thrombolysis of femoral artery thrombosis in a rabbit model. The ultrasonic frequency of 2.2 MHz and urokinase dose of 90,000 IU/kg induced optimal thrombolytic effects, while the application of either 30 min or 60 min of ultrasound exposure had similar effects. PMID:28033371

  12. Combined Low-Frequency Ultrasound and Urokinase-Containing Microbubbles in Treatment of Femoral Artery Thrombosis in a Rabbit Model.

    PubMed

    Zhu, Yanping; Guan, Lina; Mu, Yuming

    2016-01-01

    This paper aims to study the thrombolytic effect of low-frequency ultrasound combined with targeted urokinase-containing microbubble contrast agents on treatment of thrombosis in rabbit femoral artery; and to determine the optimal combination of parameters for achieving thrombolysis in this model. A biotinylated-avidin method was used to prepare microbubble contrast agents carrying urokinase and Arg-Gly-Asp-Ser (RGDS) peptides. Following femoral artery thrombosis in New Zealand white rabbits, microbubble contrast agents were injected intravenously, and ultrasonic exposure was applied. A 3 × 2 × 2 factorial table was applied to categorize the experimental animals based on different levels of combination of ultrasonic frequencies (Factor A: 1.6 MHz, 2.2 MHz, 2.8 MHz), doses of urokinase (Factor B: 90,000 IU/Kg, 180,000 IU/Kg) and ultrasound exposure time (Factor C: 30 min, 60 min). A total of 72 experimental animals were randomly divided into 12 groups (n = 6/group). Doppler techniques were used to assess blood flow in the distal end of the thrombotic femoral artery during the 120 minutes thrombolysis experiment. The rate of recanalization following thrombolysis was calculated, and thrombolytic efficacy was evaluated and compared. The thrombolytic recanalization rate for all experimental subjects after thrombolytic therapy was 68.1%. The optimal parameters for thrombolysis were determined to be 1) an ultrasound frequency of 2.2 MHz and 2) a 90,000 IU/kg dose of urokinase. Ultrasound exposure time (30 min vs. 60 min) had no significant effect on the thrombolytic effects. The combination of local low-frequency ultrasound radiation, targeted microbubbles, and thrombolytic urokinase induced thrombolysis of femoral artery thrombosis in a rabbit model. The ultrasonic frequency of 2.2 MHz and urokinase dose of 90,000 IU/kg induced optimal thrombolytic effects, while the application of either 30 min or 60 min of ultrasound exposure had similar effects.

  13. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease.

    PubMed

    Persson, Margaretha; Östling, Gerd; Smith, Gustav; Hamrefors, Viktor; Melander, Olle; Hedblad, Bo; Engström, Gunnar

    2014-01-01

    Recent studies indicate that the urokinase system could have an important role in atherogenesis and plaque rupture. The relationships among the soluble urokinase plasminogen activator receptor (suPAR), carotid plaque, and incidence of ischemic stroke and coronary artery disease (CAD) events were studied in a prospective cohort. Occurrence of carotid plaque and plasma levels of suPAR were assessed in 5166 men and women, aged 45 to 68 years, participating in the Malmö Diet and Cancer study. Incidences of ischemic stroke and CAD were monitored during a mean follow-up of 15 years. Subjects with carotid plaque had significantly higher levels of suPAR compared with those without carotid plaque. suPAR was associated with increased incidence of ischemic stroke (hazard ratio [HR] for third versus first tertile, 1.50; 95% confidence interval [CI], 1.06-2.11) and CAD (HR, 1.55; 95% CI, 1.13-2.13) after adjustment for risk factors. The risk factor-adjusted HR for ischemic stroke was 2.21 (95% CI, 1.52-3.22) in subjects with carotid plaque and high suPAR (ie, third tertile) and 1.51 (95% CI, 1.05-2.17) in subjects with carotid plaque and low suPAR compared with those without carotid plaque and low suPAR (reference). High levels of suPAR significantly increased the risk of ischemic stroke and CAD in subjects with carotid plaque. suPAR is associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke and CAD. Presence of both elevated levels of suPAR and carotid plaque increases the risk of ischemic stroke in an additive way.

  14. Intracarotid artery infusion of DTIC for invasive maxillofacial melanoma.

    PubMed

    Lejeune, F J; Jortay, A M; Dor, P

    1983-01-01

    Five inoperable invasive cases of malignant melanoma of the maxillofacial region were treated with seven intracarotid artery infusions of DTIC. Total doses of 3.5-9.5 g of DTIC were continuously administered for 15-25 days. Two of the five patients experienced transient objective regression after the first DTIC infusion but not after the second. Three patients were operated on after infusion and only one had recurrence. However, all patients died with disseminated disease within 3 years after DTIC infusion. Toxicity was encountered in two of seven infusions; it consisted in reversible leukopenia plus thrombopenia and leukopenia alone. These patients had received the highest doses, 9.5 g/25 days and 8 g/20 days respectively. It is concluded that intra-arterial infusion of DTIC can be temporarily effective in the polydisciplinary treatment of invasive head and neck melanomas.

  15. 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.

  16. Stabilization of a Percutaneously Implanted Port Catheter System for Hepatic Artery Chemotherapy Infusion

    SciTech Connect

    Shindoh, Noboru; Ozaki, Yutaka; Kyogoku, Shinsuke; Yamana, Daigo; Sumi, Yukiharu; Katayama, Hitoshi

    1999-07-15

    A port catheter system for hepatic artery infusion chemotherapy was implanted percutaneously via the left subclavian artery in 41 patients for treatment of unresectable liver metastases. The catheter tip was inserted into the gastroduodenal artery (GDA), the end hole was occluded with a guidewire fragment, and a side-hole for infusion was positioned at the bifurcation of the proper hepatic artery and the GDA. The GDA was embolized with steel coils around the infusion catheter tip via a transfemoral catheter. This procedure is designed to reduce the incidence of hepatic artery occlusion and infusion catheter dislocation.

  17. 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.

  18. [Experimental and clinical study of arterial damage induced by anti-cancer drug infusion].

    PubMed

    Ueda, E; Sako, M; Hirota, S

    1992-07-25

    In order to reduce the arterial damage following arterial chemo-infusion, arterial reaction to anti-cancer drugs and Corticosteroid were studied experimentally and clinically. In experiment, chemo-infusions (Mitomycin C, Adriamycin, Cisplatin) with or without Corticosteroid were carried out into the auricular and femoral arteries of rabbits, and the arterial changes were examined angiographically and histopathologically. The histologic examination showed the damages of various degrees characterized by intimal edema with pyknosis of endothelial cells, thrombus formation and detachment of intimal layer. The degree and frequency of the damage increased as the drug dose and concentration increased. However, higher blood flow and Corticosteroid could reduce the damages in some degrees. Clinically, bronchial arterial infusion of Cisplatin with or without Corticosteroid were studied. In conclusion, when angiography following ACI reveals narrowing and/or irregularity of the target artery, reduction of drug concentration and dose as well as elongation of infusion intervals are advised.

  19. Feeding Arteries of Primary Tongue Cancers on Intra-arterial Infusion Chemotherapy

    SciTech Connect

    Kamitani, Takeshi; Kawanami, Satoshi; Asayama, Yoshiki Matsuo, Yoshio Yonezawa, Masato Yamasaki, Yuzo; Nagao, Michinobu; Yamanouchi, Torahiko; Yabuuchi, Hidetake; Nakamura, Katsumasa; Nakashima, Torahiko; Honda, Hiroshi

    2016-02-15

    PurposeTo evaluate the frequency and the predictive factor of each feeding artery on intra-arterial infusion chemotherapy (IAIC) in primary tongue cancer.Materials and MethodsWe retrospectively evaluated 20 patients who received IAIC for primary tongue cancer. The main and accompanying feeding arteries were identified on super-selective angiography of the branches of the external carotid artery. Tumor diameter, and extension to the contralateral side, tongue extrinsic muscles (TEMs), and lateral mesopharyngeal wall were determined based on magnetic resonance imaging or computed tomography findings.ResultsThe main feeding artery was the ipsilateral lingual artery (LA) in 15 of the 20 examined tumors and the contralateral LA in the other 5. Ten cancers had only one feeding artery, and multiple feeding arteries were detected in the remaining 10. Tumors >4 cm (n = 9), those with extension to the contralateral side (n = 13), and those with extension to TEMs (n = 15) were supplied by significantly larger numbers of feeding arteries compared to tumors without these features (P = 0.01, 0.049, and 0.02, respectively). The frequency of feeding from the contralateral LA was 64 % (9/14) and 17 % (1/6) in tumors with and without extension to the contralateral side, respectively. Feeding from a facial artery (FA) was not detected in tumors ≤4 cm, while 5 of the 9 (56 %) tumors >4 cm were supplied by a FA (P = 0.01).ConclusionA careful search for feeding arteries is required, especially in large tumors with extension to the contralateral side or to TEMs.

  20. Feeding Arteries of Primary Tongue Cancers on Intra-arterial Infusion Chemotherapy.

    PubMed

    Kamitani, Takeshi; Kawanami, Satoshi; Asayama, Yoshiki; Matsuo, Yoshio; Yonezawa, Masato; Yamasaki, Yuzo; Nagao, Michinobu; Yamanouchi, Torahiko; Yabuuchi, Hidetake; Nakamura, Katsumasa; Nakashima, Torahiko; Honda, Hiroshi

    2016-02-01

    To evaluate the frequency and the predictive factor of each feeding artery on intra-arterial infusion chemotherapy (IAIC) in primary tongue cancer. We retrospectively evaluated 20 patients who received IAIC for primary tongue cancer. The main and accompanying feeding arteries were identified on super-selective angiography of the branches of the external carotid artery. Tumor diameter, and extension to the contralateral side, tongue extrinsic muscles (TEMs), and lateral mesopharyngeal wall were determined based on magnetic resonance imaging or computed tomography findings. The main feeding artery was the ipsilateral lingual artery (LA) in 15 of the 20 examined tumors and the contralateral LA in the other 5. Ten cancers had only one feeding artery, and multiple feeding arteries were detected in the remaining 10. Tumors >4 cm (n = 9), those with extension to the contralateral side (n = 13), and those with extension to TEMs (n = 15) were supplied by significantly larger numbers of feeding arteries compared to tumors without these features (P = 0.01, 0.049, and 0.02, respectively). The frequency of feeding from the contralateral LA was 64 % (9/14) and 17 % (1/6) in tumors with and without extension to the contralateral side, respectively. Feeding from a facial artery (FA) was not detected in tumors ≤4 cm, while 5 of the 9 (56 %) tumors >4 cm were supplied by a FA (P = 0.01). A careful search for feeding arteries is required, especially in large tumors with extension to the contralateral side or to TEMs.

  1. 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.

  2. Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).

    PubMed Central

    Wilson, J; Silverton, N P; Baig, M W; Perrins, E J; Smith, D R; Davies, J A; Prentice, C R

    1988-01-01

    Because epoprostenol (prostacyclin) is a prostaglandin that causes vasodilatation and inhibits platelet function it may be of benefit during coronary artery angioplasty. The safety and capacity of intracoronary epoprostenol to dilate coronary arteries were assessed in 16 patients undergoing routine coronary angiography. The view that best displayed the left epicardial coronary arteries was selected as a control for each patient. Intracoronary epoprostenol was then given and the angiogram was repeated in the chosen view. The procedure was repeated twice: once with a higher dose of epoprostenol and once after intracoronary isosorbide dinitrate. Angiograms were coded and analysed by an observer who was unaware of the treatment. The calibre of the arteries was measured from traced projections of the angiograms. The blood pressure, heart rate, and electrocardiogram were recorded throughout. The first two patients were given epoprostenol infusions of 2.5 and 5.0 ng/kg per minute to assess safety, and there were no untoward reactions. The next ten patients had epoprostenol infusions of 5.0 and 7.5 ng/kg per minute followed by intracoronary isosorbide dinitrate. No haemodynamic disturbances occurred and coronary luminal calibre did not change with epoprostenol (mean (SD) luminal diameter: 2.85 (0.62) mm control, 2.80 (0.61) mm at 5.0 ng/kg, and 2.80 (0.54) mm at 7.5 ng/kg), but it did increase significantly with isosorbide dinitrate (to 3.17 (0.36) mm). The last four patients had epoprostenol infusions of 7.5 and 10 ng/kg followed by intracoronary isosorbide dinitrate and two of them became hypotensive (one after epoprostenol and one after isosorbide dinitrate). Coronary luminal calibre did not change significantly (3.5 (0.45) mm control, 2.96 (0.81) mm at 7.5 ng/kg, 3.45 (0.96) mm at 10 ng/kg, and 3.20 (0.61) mm with isosorbide dinitrate). Eight patients developed tall T waves on the electrocardiogram during epoprostenol infusion but none had arrhythmias. The results

  3. 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

  4. 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.

  5. [The intra-arterial infusion. II. Its use in the treatment of septic gangrene].

    PubMed

    Hugeneck, J; Gottlob, R

    1982-11-15

    The local toxicity of Cefazolin was evaluated for the arterial endothelium. 37 patients with septic gangrena were treated by intraarterial infusions of standardized Cefazolin infusions into the arteries of the involved legs. In the average 11.6 infusions were applied for one leg. The bacteriology of the infected gangrenous legs is discussed as well as the sensitivity of antibiotics of the germs found. A progression of the gangrena could be prevented in 78% of the cases, only minor surgical measures, such as borderline amputations or plastic interventions were necessary. No side effects due to the local application of the drug were observed. The intraarterial continuous infusion of broad band antibiotics for septic gangrena is recommended.

  6. Boundary layer infusion of basic fibroblast growth factor accelerates intimal hyperplasia in endarterectomized canine artery.

    PubMed

    Chen, C; Li, J; Mattar, S G; Pierce, G F; Aukerman, L; Hanson, S R; Lumsden, A B

    1997-05-01

    We examined the effects of human recombinant basic fibroblast growth factor (bFGF) on the proliferation and migration of cultured dog smooth muscle cells (SMCs) and endothelial cells (ECs) and the effect of continuous local boundary layer infusion of bFGF on intimal hyperplasia in endarterectomized dog artery. In vitro proliferation and migration of dog SMCs or ECs were performed using direct counting and Boyden's chamber, respectively. At a dose of 10 ng/mL, bFGF significantly promoted both SMC and EC proliferation (7- and 4-fold, respectively) and migration (2.3- and 1.9-fold, respectively). Six dogs underwent bilateral carotid endarterectomies. A newly designed local infusion device with an osmotic pump continuously delivered bFGF to one artery or vehicle solution to the contralateral artery for 14 days. The intimal thickness and area in the bFGF-treated vessels were increased by 72 and 81%, respectively, compared with control arteries (P < 0.05). As assessed by the bromodeoxyuridine index, the proliferative activity was increased by 73% in bFGF-treated arteries (P = 0.03). Furthermore, cell proliferation at the distal anastomoses of local infusion device was significantly increased in the bFGF-infused grafts compared with distal anastomoses in the control grafts (13.24 +/- 1.24% versus 5.24 +/- 1.01%, P < 0.01). These data demonstrate that human recombinant bFGF has a potent effect on dog SMC and EC proliferation and migration, and that local infusion of exogenous bFGF significantly enhances the intimal hyperplasia formation and cell proliferation to vascular injury. We conclude that the bFGF pathway may contribute to the development of intimal hyperplastic lesions.

  7. Renal function in sheep during infusion of alkali metal ions into the renal artery.

    PubMed Central

    Beal, A M; Harrison, F A

    1975-01-01

    1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron. PMID:236381

  8. Ascorbic acid improves postischemic vasodilatation impaired by infusion of soybean oil into canine iliac artery.

    PubMed

    Osanai, H; Okumura, K; Hayakawa, M; Harada, M; Numaguchi, Y; Mokuno, S; Murase, K; Matsui, H; Toki, Y; Ito, T; Hayakawa, T

    2000-12-01

    This study was conducted to (a) assess postischemic vasodilatation by changes in the vascular cross-sectional area using simultaneous intravascular two-dimensional and Doppler ultrasound before and after the infusion of Intralipid (Pharmacia & Upjohn, Peapack, NJ, U.S.A.); (b) evaluate how antioxidant ascorbic acid modifies the effects of Intralipid on postischemic vasodilatation: and (c) clarify the changes in plasma nitrite and nitrate (NOx-) levels after the infusion of Intralipid with and without ascorbic acid. Twenty-eight mongrel dogs were used to measure for vascular cross-sectional area and average instantaneous peak velocity in the iliac arteries after the 5-min occlusion of the arteries. Postischemic vasodilatation was impaired after the infusion of Intralipid (20%, 2 ml/kg) and this impaired response was reversed by the co-administration of ascorbic acid (30 mg/kg). NG-monomethyl-L-arginine completely abolished postischemic vasodilatation. Plasma NOx levels were significantly reduced after the infusion of Intralipid compared with baseline (11.6+/-0.4 vs. 12.9+/-0.3 microM, p = 0.025) and after infusion of Intralipid with ascorbic acid compared with baseline (11.8+/-0.5 vs. 13.1+/-0.4 microM, p = 0.047). We concluded that ascorbic acid reverses the endothelial dysfunction induced by Intralipid without increasing plasma NOx- levels and that deactivation of nitric oxide by oxidative stress is a primary contributor to Intralipid-induced impaired vasodilation.

  9. Unchanged plasma levels of the soluble urokinase plasminogen activator receptor in elective coronary artery bypass graft surgery patients and cardiopulmonary bypass use.

    PubMed

    Gozdzik, Waldemar; Adamik, Barbara; Gozdzik, Anna; Rachwalik, Maciej; Kustrzycki, Wojciech; Kübler, Andrzej

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) has been recently recognized as a potential biological marker of various disease states, but the impact of a major surgical intervention on the suPAR level has not yet been established. The aim of our study was to investigate if the induction of a systemic inflammatory reaction in response to cardiopulmonary bypass would be accompanied by an increase in the plasma suPAR level. Patients undergoing coronary artery bypass grafting under cardiopulmonary bypass (CPB) were added. Based on the baseline suPAR level, patients were divided into group 1 (suPAR within normal range) or group 2 (suPAR above range). Blood was collected before the induction of anesthesia and 6 and 24 hours after surgery. Plasma suPAR, IL-6, IL-8, TNF-α, troponin I, NT-proBNP, and NGAL were quantified to assess the impact of surgical trauma on these markers. The baseline suPAR level was within the normal range in 31 patients (3.3 ng/mL), and elevated in 29 (5.1 ng/mL) (p<0.001). Baseline mediators of systemic inflammatory reaction concentrations (IL-6, TNF-α, and IL-8) and organ injury indices (troponin I, NT-proBNP, and NGAL) were low and increased after surgery in all patients (p<0.05). The surgery did not cause significant changes in the suPAR level either at 6 or 24 hours after, however the difference between groups observed at baseline remained substantial during the postoperative period. There was no change in the suPAR level observed in patients subjected to elective cardiac coronary artery bypass surgery and CPB, despite activation of a systemic inflammatory reaction.

  10. Bronchial artery infusion of mitomycin C in carcinoma of the lung

    SciTech Connect

    Ekholm, S.; Albrechtsson, U.; Tylen, U.

    1983-06-01

    Fifteen patients with bronchial carcinoma were treated with infusions of 10 mg Mitomycin C (MMC) in the bronchial artery feeding the tumor. The treatment was repeated three times with 2-3 weeks interval between treatments. Half of the patients then received radiation to the tumor area and mediastinum. All tumors decreased in size, complete remission occurred in two and partial remission in five patients. Survival time, however, was not prolonged and esophageal complications occurred in several patients.

  11. Visual recovery and OCT evolution following central retinal artery occlusion treated with intra-arterial verapamil and alteplase infusion.

    PubMed

    Kovach, Jaclyn L; Mason, Brian

    2015-01-01

    A 69-year-old woman presented with a "veil" over the left eye. Clinical examination demonstrated signs of central retinal artery occlusion. Visual acuity was compromised to 1/200 E in the left eye. Ocular massage and anterior chamber paracentesis failed to improve vision. An emergent intra-arterial catheterization with verapamil and alteplase infusion was performed less than 12 hours following symptom onset. Initial optical coherence tomography (OCT) showed inner retinal edema. One year later, OCT revealed relatively minor thinning, which could explain the patient's visual recovery to 20/40. This may be the first article to report OCT changes following this treatment for central retinal artery occlusion. Copyright 2015, SLACK Incorporated.

  12. [Radiofrequency ablation therapy combined with intrahepatic arterial infusion chemotherapy for liver metastasis of colorectal cancer].

    PubMed

    Otsuka, Shinya; Inagaki, Masaru; Miyoshi, Kazuya; Takahashi, Masahiko; Oosaki, Toshihide; Fuchimoto, Sadanori; Sakata, Tatsuhiko

    2003-10-01

    We performed radiofrequency ablation (RFA) therapy combined with intrahepatic arterial infusion chemotherapy for 7 patients with liver metastasis from colorectal cancer. Synchronous metastasis accounted for 5 cases and metachronous for 2 cases. Two cases were H1, 2 cases H2, and 3 cases H3. Following the resection of colorectal primary lesion, we performed RFA for liver metastasis, using a Cool-tip electrode purchased from Radionics (Burlington, MA, USA). The mean number of sessions per patient was 5.1 (1-10). Ablation time of each session was changed according to tumor size, as follows: less than 1 cm in diameter: 2 min, 2 cm: 5 min, 2.5 cm: 10 min. By using intra-operative catheterization, weekly intrahepatic arterial infusion chemotherapy was performed for liver metastasis. Excellent ablation was achieved in all cases by CT evaluation and no significant side-effect was observed. Average observation period was 15 months (maximal survival period was 31 months) and 6 patients are alive. RFA therapy combined with intrahepatic arterial infusion chemotherapy achieved excellent therapeutic effect, and maintained good quality of life in patients.

  13. Pharmacokinetic evaluation of pancreatic arterial infusion chemotherapy after unification of the blood supply in an animal model.

    PubMed

    Tanaka, Toshihiro; Yamamoto, Kiyosei; Sho, Masayuki; Nishiofuku, Hideyuki; Inoue, Masayoshi; Sueyoshi, Satoru; Anai, Hiroshi; Sakaguchi, Hiroshi; Nakajima, Yoshiyuki; Kichikawa, Kimihiko

    2010-01-01

    The purpose of this study was to investigate the potential pharmacokinetic advantage of pancreatic arterial infusion chemotherapy of 5-fluorouracil (5-FU) with temporary unification of the pancreatic blood supply for advanced pancreatic cancer in an animal model. Nine pigs were divided into three groups of three pigs each. 5-FU (20 mg/kg) was infused via jugular vein (group I), celiac artery (group II), and celiac artery with balloon occlusion of the superior mesenteric artery (SMA; group III). At 0, 10, 30, and 60 minutes after drug infusion, the concentrations of 5-FU were measured in plasma and tissues including the liver, pancreatic head, pancreatic uncinate process, and duodenum. Areas under the concentration-time curve (AUCs) were calculated and statistically compared. The temporary unification of the pancreatic blood supply by converting from dual blood supply through the celiac artery and SMA into a single celiac arterial supply was confirmed by dye injection. Mean AUCs in the pancreas head and liver were significantly higher for groups II and III compared with group I (P < .05). In contrast, there were no significant differences in plasma 5-FU concentrations between groups. In addition, the AUC in the pancreatic uncinate process was significantly higher for group III compared with groups I and II (P < .05). Pancreatic arterial infusion chemotherapy allows efficient regional drug delivery into the pancreas and liver. Importantly, the unification of the pancreatic blood supply may be required to induce maximum efficacy of arterial infusion chemotherapy for the tumor in the pancreatic uncinate process.

  14. 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

  15. Improved arterial blood oxygenation following intravenous infusion of cold supersaturated dissolved oxygen solution.

    PubMed

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

    2014-01-01

    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. 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. 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. 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.

  16. 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.

  17. Impact of multislice CT angiography on planning of radiological catheter placement for hepatic arterial infusion chemotherapy.

    PubMed

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

    2008-01-01

    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.

  18. Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III colorectal cancer: a retrospective study

    PubMed Central

    Wang, Yao; Sun, Xin Rong; Feng, Wen Ming; Bao, Ying; Zheng, Yin Yuan

    2016-01-01

    Background Radical resection is the main treatment for colorectal cancer (CRC), but metastasis or recurrence is common in which liver metastasis accounted for 83% of the cases. Therefore, the prognosis of patients with advanced CRC may be improved if liver metastasis is prevented. This study aims to investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of stage III CRC patients after curative resection. Methods Between 2002 and 2008, 287 stage III CRC patients who had undergone radical resection were included in this study. According to postoperative adjuvant chemotherapy modality, these patients were divided into two groups. Patients in the combined therapy group received two cycles of HAIC plus four cycles of systemic chemotherapy, while patients in the monotherapy group received six cycles of systemic chemotherapy alone. The HAIC regimen consisted of hepatic arterial infusion of oxaliplatin (OXA, 85 mg/m2) on day 1 and 5-fluorouracil (5-FU, 2,400 mg/m2) on days 2 and 3 followed by a vein infusion of folinic acid (FA, 200 mg/m2) as a 2-hour infusion on days 2 and 3. The systemic chemotherapy regimen consisted of a 2-hour infusion of OXA (85 mg/m2) on day 1 followed by FA (200 mg/m2) as a 2-hour infusion on days 2 and 3, and by 5-FU (2,400 mg/m2) as a 48-hour infusion. This was repeated every 4 weeks. All cases were followed up for 5 years or until death. The 5-year overall survival, disease-free survival, liver metastases-free survival, and the overall liver metastases rates were retrospectively compared. Results Significant differences were found in the 5-year overall survival (combined therapy, 70.71%; monotherapy, 57.14%; P=0.014), disease-free survival (combined therapy, 69.29%; monotherapy, 55.78%; P=0.021), and liver metastases-free survival rates (combined therapy, 70%; monotherapy, 56.46%; P=0.019). Conclusion Prophylactic adjuvant HAIC can prevent metachronous liver metastases and improve the prognosis of patients

  19. Comparison of dose regimens for the administration of recombinant pro-urokinase in a canine thrombosis model.

    PubMed

    Burke, S E; Lubbers, N L; Nelson, R A; Henkin, J

    1997-05-01

    Pro-urokinase represents an important addition to the array of thrombolytic drugs currently available for clinical use because of its high clot specificity but distinctly different mechanism compared with that of t-PA. Recombinant pro-urokinase (r-proUK) is a single-chain precursor of high molecular weight urokinase which has been expressed in a mouse myeloma cell line. The present study was conducted to determine the dosing regimen which would produce optimal clot lysis and restoration of blood flow 2 h after treatment with r-proUK, using a dog model of arterial thrombosis. Efficacy was indicated by lysis of a radio-labelled clot which was formed in the heat-damaged femoral arteries of 39 male beagle dogs. The animals were divided into six heparinized treatment groups, each receiving one of five dosing regimens or the vehicle for r-proUK. The total dose (80,000 U/kg) was divided into an initial loading bolus, followed by either a second bolus or by infusions for various time periods, as shown below: Group Treatment Regimen % Lysis 1 r-proUK Bolus/bolus, 50%/50% at 0 and 15 min 52 +/- 7 2 r-proUK Bolus/bolus, 50%/50% at 0 and 30 min 62 +/- 7 3 r-proUK Bolus/infusion, 20%/80% infused to 30 min 41 +/- 8 4 r-proUK Bolus/infusion, 20%/80% infused to 60 min 66 +/- 5 5 r-proUK Bolus/infusion, 50%/50% infused to 30 min 73 +/- 4 6 Vehicle Bolus/infusion, 50%/50% infused to 30 min 12 +/- 6 It was concluded that optimal clot lysis and restoration of femoral flow was accomplished using a regimen in which 50% of the dose was given as a bolus, followed immediately by the remaining 50% given as a 30 min intravenous infusion (Group 5). At the dose used in this study, r-proUK did not produce degradation of fibrinolytic or hemostatic plasma proteins.

  20. Clinical Variables Correlated with Numbers of Intra-arterial Nimodipine Infusion in Patients with Medically Refractory Cerebral Vasospasm

    PubMed Central

    Kim, Sang-Young; Kim, Ki-Hong; Cho, Jae-Hoon

    2015-01-01

    Objective The objective of this study was to find out the clinical variables correlated with repeated intra-arterial (IA) nimodipine infusions in patients with medically refractory cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH). Materials and Methods During the 36 months between January 2011 and December 2013, 275 patients were treated at our institute for SAH due to a ruptured intracranial aneurysm. Of the 275 patients, 26 patients (9.5%) met the inclusion criteria. For each patient, a retrospective review of their medical records was conducted. Results Eleven patients underwent a single IA nimodipine infusion and 15 patients underwent more than two IA nimodipine infusions. Multiple IA nimodipine infusion patients had poor improvement (2 of 15 patients, 13.3%) in Glasgow coma scale (GCS) scores after the first IA nimodipine infusion compared to patients of single IA nimodipine infusion (6 of 11 patients, 54.6%) (p = 0.038). The mean middle cerebral artery (MCA) Lindegaard ratio of multiple IA nimodipine infusion patients was 4.3 ± 1.1 after the first IA nimodipine infusion (p = 0.039). In multiple IA nimodipine infusion patients, CV occurred more often bilaterally (p = 0.035) and distally (p = 0.001). More vessel segments were affected in multiple IA nimodipine infusion patients (3.1 ± 1.0) (p < 0.001). Conclusion The following factors correlated with multiple IA nimodipine infusions: 1) no improvement in GCS after the IA nimodipine infusion; 2) no decrease of MCA velocity on transcranial doppler over 50 cm/s or Lindegaard ratio over 4.3 after the IA nimodipine infusion; 3) distal, bilateral, or diffuse involvement of CV. PMID:26523251

  1. Convulsion during intra-arterial infusion of fasudil hydrochloride for the treatment of cerebral vasospasm following subarachnoid hemorrhage.

    PubMed

    Enomoto, Yukiko; Yoshimura, Shinichi; Yamada, Kiyofumi; Iwama, Toru

    2010-01-01

    The incidence of convulsion and associated factors were retrospectively analyzed in 23 patients with symptomatic cerebral vasospasm following subarachnoid hemorrhage (SAH) who underwent a total of 31 intra-arterial infusion of fasudil hydrochloride (IAFH) procedures in 49 vessels. Fasudil hydrochloride was administered by superselective infusion via a microcatheter positioned at the proximal portion of the affected artery. Thirteen procedures were performed by manually controlled infusion of 30-75 mg fasudil hydrochloride (1.2-3.75 mg/ml) for approximately 10 minutes. Eighteen procedures were performed by continuous infusion of 60 mg fasudil hydrochloride (1.2 mg/ml) by infusion pump at a constant rate of 3 mg/min. Neurological improvement was observed after 18 of 22 procedures in patients with neurological deterioration due to vasospasm. Convulsion during IAFH developed in 4 patients, all treated by manual infusion (p < 0.05). The manual infusion method (p < 0.05) and infusion rate greater than 3 mg/min (p < 0.01) were significantly associated with the incidence of convulsion during IAFH. IAFH was effective for treating cerebral vasospasm following aneurysmal SAH. IAFH at a constant rate of 3 mg/min delivered by infusion pump improved the symptoms of cerebral vasospasm and prevented convulsions during IAFH.

  2. The effect of intrafetal infusion of metyrapone on arterial blood pressure and on the arterial blood pressure response to angiotensin II in the sheep fetus during late gestation

    PubMed Central

    Warnes, K E; Coulter, C L; Robinson, J S; McMillen, I C

    2003-01-01

    While the impact of exogenous glucocorticoids on the fetal cardiovascular system has been well defined, relatively few studies have characterised the role of endogenous fetal glucocorticoids in the regulation of arterial blood pressure (BP) during late gestation. We have therefore infused metyrapone, an inhibitor of cortisol biosynthesis, into fetal sheep from 125 days gestation (when fetal cortisol concentrations are low) and from 137 days gestation (when fetal cortisol concentrations are increasing) and measured fetal plasma cortisol, 11-desoxycortisol and ACTH, fetal systolic, diastolic and mean arterial BP, heart rate, and the fetal BP responses to increasing doses of angiotensin II (AII). At 125 days gestation, there was a significant increase in fetal plasma ACTH and 11-desoxycortisol by 24 h after (+24 h) the start of the metyrapone infusion, and plasma cortisol concentrations were not different at +24 h when compared with pre-infusion values. Whilst the initial fall in circulating cortisol concentrations may have been transient, systolic, diastolic and mean arterial BP were ∼5–6 mmHg lower (P < 0.05) in metyrapone- than in vehicle-infused fetuses at 24–48 h after the start of the infusion. When metyrapone was infused from 137/138 days gestation, there was a significant decrease in plasma cortisol concentrations by +6 h, which was followed by an increase back to pre-infusion values. While cortisol concentrations decreased, there was no change in fetal mean arterial BP during the first 24 h after the start of metyrapone infusion. Mean fetal arterial BP values at 137–139 days gestation were not different in fetuses that had been infused with either vehicle or metyrapone from 125 days gestation or with metyrapone from 137–138 days gestation. At 137–139 days gestation, however, arterial BP responses to increasing doses of AII were significantly blunted in fetuses that had been infused with metyrapone from 125 days gestation, when compared with

  3. Radiation dose reduction in intra-arterial chemotherapy infusion for intraocular retinoblastoma.

    PubMed

    Cooke, Daniel L; Stout, Charles E; Kim, Warren T; Hetts, Steven W; Higashida, Randall T; Halbach, Van V; Dowd, Christopher F; Gould, Robert G

    2014-12-01

    Retinoblastoma (RB) is a rare malignancy affecting the pediatric population. Intravenous chemotherapy is the longstanding delivery method, although intra-arterial (IA) chemotherapy is gaining popularity given the reduced side effects compared with systemic chemotherapy administration. Given the sensitivity of the target organ, patient age, and secondary tumor susceptibility, a premium has been placed on minimizing procedural related radiation exposure. To reduce patient x-ray dose during the IA infusion procedure, customized surgical methods and fluoroscopic techniques were employed. The routine fluoroscopic settings were changed from the standard 7.5 pulses/s and dose level to the detector of 36 nGy/pulse, to a pulse rate of 4 pulses/s and detector dose to 23 nGy/pulse. The angiographic dose indicators (reference point air kerma (Ka) and fluoroscopy time) for a cohort of 10 consecutive patients (12 eyes, 30 infusions) were analyzed. An additional four cases (five eyes, five infusions) were analyzed using dosimeters placed at anatomic locations to reflect scalp, eye, and thyroid dose. The mean Ka per treated eye was 20.1±11.9 mGy with a mean fluoroscopic time of 8.5±4.6 min. Dosimetric measurements demonstrated minimal dose to the lens (0.18±0.10 mGy). Measured entrance skin doses varied from 0.7 to 7.0 mGy and were 73.4±19.7% less than the indicated Ka value. Ophthalmic arterial melphalan infusion is a safe and effective means to treat RB. Modification to contemporary fluoroscopic systems combined with parsimonious fluoroscopy can minimize radiation exposure. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Efficacy of chemotherapy combined with targeted arterial infusion of verapamil in patients with advanced gastric cancer.

    PubMed

    Ning, Zhongliang; Chen, Dong; Liu, Aiguo; Fan, Pingsheng; Duan, Qiaohong; Zhang, Tengyue; Fan, Gaofei

    2014-01-01

    The present study evaluated the efficacy of chemotherapy combined with targeted arterial infusion of verapamil in patients with advanced gastric cancer. Forty patients were enrolled. Targeted arterial infusion of verapamil was done once a month, 3-5 times per patient, along with chemotherapy. After 2 bouts of combined treatment, the efficacy was evaluated. Primary gastric tumor was confirmed in 38/40 patients, and unconfirmed in 2/40 patients due to adhesion of tumors to surrounding tissue. Combined treatment was administered in 38 patients with defined tumors. Complete response to the treatment was in 5/38 (13.1 %) patients, partial response in 27/38 (71.1 %) patients, stable disease in 4/38 (10.5 %) patients, and progressive disease in 2/38 (5.26 %) patients. The effective rate (i.e., complete + partial response) comprised 84.2 %. There were 31 patients with liver metastases; 10/31 (32.3 %) patients showed complete response, 16/31 (51.6 %) patients showed partial response, 3/31 (9.7 %) patients had stable disease, and 2/31 (6.5 %) patients had progressive disease. The effective rate in these patients was 83.8 %. Thirty-seven patients were followed up, and 27/37 (73.0 %) patients were alive for 6 months or longer, 19/37 (51.3 %) for 12 months, 8 (35.1 %) for 18 months, and 8/37 (21.6 %) for 24 months. In conclusion, in patients with advanced gastric cancer, chemotherapy is more effective when combined with targeted arterial infusion of verapamil, leading to extended patients' survival and improved quality of life.

  5. Iloprost infusion in diabetic patients with peripheral arterial occlusive disease and foot ulcers.

    PubMed

    Mirenda, Francesco; La Spada, Michele; Baccellieri, Domenico; Stilo, Francesco; Benedetto, Filippo; Spinelli, Francesco

    2005-01-01

    The aim of the study was to evaluate iloprost infusion as an alternative to open surgical revascularisation in diabetic patients with foot ulcers, also as a support measure in conjunction with endovascular procedures. We studied 244 patients with critical ischaemia of the lower limbs, 146 of whom (59.8%) affected by diabetes. A femoro-distal bypass was performed in 175 patients. In the 69 nonsurgical diabetic patients (47.3% of the diabetics) an iloprost infusion was started. These diabetics presented foot ulcers, a palpable or slightly hypo-sphygmic popliteal pulse and high distal arterial flow at the ankle. In 55 of these patients (79.7% of those not operated on and 37.6% of the diabetics) who were non-responders to medical therapy, an endovascular procedure was also performed. The results of the iloprost infusion (69 pts.) were evaluated after one week. In 14 responders treated only with iloprost infusion, complete healing of the lesions occurred during the 3 weeks following the end of the 4-week course of therapy. No severe ischaemia recurrences were reported in the follow-up of these 69 patients. In the 47.3% of subjects with diabetic arteriopathy presenting foot ulcers and high distal flow, it proved possible to avoid an open surgical revascularisation procedure and to resort to medical therapy with iloprost, completed in 79.7% of cases with endovascular procedures. Iloprost infusion improves limb perfusion and, in selected cases may be an important therapeutic tool for the care of ulcerative lesions of the diabetic foot, also as a support measure in conjunction with endovascular procedures.

  6. Overexpression of endothelial nitric oxide synthase improves endothelium-dependent vasodilation in arteries infused with helper-dependent adenovirus.

    PubMed

    Jiang, Bo; Du, Liang; Flynn, Rowan; Dronadula, Nagadhara; Zhang, Jingwan; Kim, Francis; Dichek, David

    2012-11-01

    Adenoviral vectors (Ad) are useful tools for in vivo gene transfer into endothelial cells. However, endothelium-dependent vasodilation is impaired after Ad infusion, and this impairment is not prevented by use of advanced-generation "helper-dependent" (HD) Ad that lack all viral genes. We hypothesized that endothelium-dependent vasodilation could be improved in Ad-infused arteries by overexpression of endothelial nitric oxide synthase (eNOS). We tested this hypothesis in hyperlipidemic, atherosclerosis-prone rabbits because HDAd will likely be used for treating and preventing atherosclerosis. Moreover, the consequences of eNOS overexpression might differ in normal and atherosclerosis-prone arteries and could include atherogenic effects, as reported in transgenic mice. We cloned rabbit eNOS and constructed an HDAd that expresses it. HDAdeNOS increased NO production by cultured endothelial cells and increased arterial eNOS mRNA in vivo by ∼10-fold. Compared to arteries infused with a control HDAd, HDAdeNOS-infused arteries of hyperlipidemic rabbits had significantly improved endothelium-dependent vasodilation, and similar responses to phenylephrine and nitroprusside. Moreover, infusion of HDAdeNOS had local atheroprotective effects including large, significant decreases in intimal lipid accumulation and arterial tumor necrosis factor (TNF)-α expression (p≤0.04 for both). HDAdeNOS infusion yields a durable (≥2 weeks) increase in arterial eNOS expression, improves vasomotor function, and reduces artery wall inflammation and lipid accumulation. Addition of an eNOS expression cassette improves the performance of HDAd, has no harmful effects, and may reduce atherosclerotic lesion growth.

  7. Overexpression of Endothelial Nitric Oxide Synthase Improves Endothelium-Dependent Vasodilation in Arteries Infused with Helper-Dependent Adenovirus

    PubMed Central

    Jiang, Bo; Du, Liang; Flynn, Rowan; Dronadula, Nagadhara; Zhang, Jingwan; Kim, Francis

    2012-01-01

    Abstract Adenoviral vectors (Ad) are useful tools for in vivo gene transfer into endothelial cells. However, endothelium-dependent vasodilation is impaired after Ad infusion, and this impairment is not prevented by use of advanced-generation “helper-dependent” (HD) Ad that lack all viral genes. We hypothesized that endothelium-dependent vasodilation could be improved in Ad-infused arteries by overexpression of endothelial nitric oxide synthase (eNOS). We tested this hypothesis in hyperlipidemic, atherosclerosis-prone rabbits because HDAd will likely be used for treating and preventing atherosclerosis. Moreover, the consequences of eNOS overexpression might differ in normal and atherosclerosis-prone arteries and could include atherogenic effects, as reported in transgenic mice. We cloned rabbit eNOS and constructed an HDAd that expresses it. HDAdeNOS increased NO production by cultured endothelial cells and increased arterial eNOS mRNA in vivo by ∼10-fold. Compared to arteries infused with a control HDAd, HDAdeNOS-infused arteries of hyperlipidemic rabbits had significantly improved endothelium-dependent vasodilation, and similar responses to phenylephrine and nitroprusside. Moreover, infusion of HDAdeNOS had local atheroprotective effects including large, significant decreases in intimal lipid accumulation and arterial tumor necrosis factor (TNF)-α expression (p≤0.04 for both). HDAdeNOS infusion yields a durable (≥2 weeks) increase in arterial eNOS expression, improves vasomotor function, and reduces artery wall inflammation and lipid accumulation. Addition of an eNOS expression cassette improves the performance of HDAd, has no harmful effects, and may reduce atherosclerotic lesion growth. PMID:22906141

  8. Delivery of anti-platelet-endothelial cell adhesion molecule single-chain variable fragment-urokinase fusion protein to the cerebral vasculature lyses arterial clots and attenuates postischemic brain edema.

    PubMed

    Danielyan, Kristina; Ding, Bi-Sen; Gottstein, Claudia; Cines, Douglas B; Muzykantov, Vladimir R

    2007-06-01

    Efficacy and safety of current means to prevent cerebrovascular thrombosis in patients at high risk of stroke are suboptimal. In theory, anchoring fibrinolytic plasminogen activators to the luminal surface of the cerebral endothelium might arrest formation of occlusive clots in this setting. We tested this approach using the recombinant construct antiplatelet-endothelial cell adhesion molecule (PECAM) single-chain variable fragment (scFv)-urokinase-type plasminogen activator (uPA), fusing low-molecular-weight single-chain urokinase-type plasminogen activator with a scFv of an antibody directed to the stably expressed endothelial surface determinant PECAM-1, implicated in inflammation and thrombosis. Studies in mice showed that scFv-uPA, but not unconjugated uPA 1) accumulates in the brain after intravascular injection, 2) lyses clots lodged in the cerebral arterial vasculature without hemorrhagic complications, 3) provides rapid and stable cerebral reperfusion, and 4) alleviates post-thrombotic brain edema. Effective and safe thromboprophylaxis in the cerebral arterial circulation by anti-PECAM scFv-uPA represents a prototype of a new paradigm to prevent recurrent cerebrovascular thrombosis.

  9. Hepatic artery infusion therapy is effective for chemotherapy-resistant liver metastatic colorectal cancer.

    PubMed

    Goi, Takanori; Naruse, Takayuki; Kimura, Youhei; Fujimoto, Daisuke; Morikawa, Mitsuhiro; Koneri, Kenji; Yamaguchi, Akio

    2015-10-09

    Systemic FOLFOX (folinic acid (leucovorin (LV)), 5-fluorouracil (5-FU), and oxaliplatin), FOLFIRI (LV, 5-FU, and irinotecan), or FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) chemotherapy regimens and additional molecular-target treatments, including anti-vascular endothelial growth factor, anti-epidermal growth factor receptor, and anti-multi-kinase antibodies, have been recommended for unresectable recurrent colorectal cancers. However, no effective treatments are currently available for cases refractory to these therapies. Therefore, the development of alternative therapies is desired. In the present study, we administered and observed the effectiveness of hepatic artery infusion therapy (HAIC) in patients with unresectable liver metastatic colorectal cancers refractory to systemic chemotherapy. In addition, we observed that in an experimental system with anticancer drug-resistant colorectal cancer lines, apoptosis and cell death could be induced by increasing anticancer drug concentrations. The subjects had liver metastatic colorectal cancers that were unresponsive to systemic chemotherapy (FOLFOX/FOLFIRI) or to additional molecular-target therapies for progressive disease. Hepatic infusion tube placement was conducted according to the Seldinger method to insert a catheter with a side hole via the right femoral artery. A coiling procedure was performed to prevent drug influx into the gastroduodenal artery. Ten subjects were selected, and the results were evaluated after HAIC (5-FU and LV administered once weekly). Moreover, anticancer drug-resistant colorectal cancer lines were subsequently prepared to investigate whether increased anticancer drug concentrations could induce apoptosis or cell death. Of the 10 subjects, 3 (30 %) showed partial response and 4 (40 %) showed no change according to computed tomography imaging findings obtained after hepatic artery infusion. The disease control rate was 70 %. Eight subjects had improved quality of life

  10. Improving the visual field in coronary artery by with non-obstructive angioscopy: dual infusion method.

    PubMed

    Komatsu, Sei; Ohara, Tomoki; Takahashi, Satoru; Takewa, Mitsuhiko; Yutani, Chikao; Kodama, Kazuhisa

    2017-02-07

    Non-obstructive angioscopy (NOA) is used to visualize the surface of the coronary artery, and a clear visual field is obtained by injecting transparent fluid into the gap between the probing catheter and the fiber. This study examines visual field expansion by a dual infusion method, which involves an infusion from the probing and guiding catheters, and the relationships between visual grade and vessel characteristics. Thirty-two patients and thirty patients performed coronary plaque analysis with NOA using the conventional method and the novel dual infusion method, respectively. Images were blindly analyzed retrospectively. Visual fields were assessed from image slices using a 5-point scale (0 = invisible, 1 = poor, 2 = adequate, 3 = good, 4 = excellent) at 5-s intervals. The relationships between visual grade and vessel characteristics were analyzed using multiple stepwise linear regression analysis. The mean visual grade, "excellent" ratio, and "adequate" ratio were significantly higher using the dual infusion method than those obtained using the conventional method (p = 0.003, p = 0.004, and p = 0.005 respectively). The "invisible" ratio was significantly lower using the dual infusion method than the conventional method (p = 0.027). The visual field was negatively associated with the conventional method (β  = -0.154, p < 0.001), large vessels (β = -0.004, p < 0.49), bifurcation (β  = -0.205, p < 0.001), vessels with a sharp angle (β  = -0.106, p < 0.001), in-stent (β = -0.180, p < 0.001), and distal border of stent (β  = -0.075, p < 0.001); and positively associated with significant stenosis (β  = 0.072, p < 0.001) and significantly covered stents (β  = 0.050, p = 0.018). The visual field with NOA can be effectively expanded by the dual infusion method.

  11. 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.

  12. Intra-arterial and Intravenous Tirofiban Infusion for Thromboembolism during Endovascular Coil Embolization of Cerebral Aneurysm.

    PubMed

    Kim, Sang Heum; Kim, Tae Gon; Kong, Min Ho

    2017-09-01

    Thromboembolism is the one of the most serious complications that can occur during endovascular coil embolization of cerebral aneurysm. We report on the effectiveness and safety of intra-arterial/intravenous (IA/IV) glycoprotein IIb/IIIa inhibitor (tirofiban) infusion for treating thromboembolism during endovascular coil embolization of cerebral aneurysm. We performed a retrospective analysis of 242 patients with ruptured or unruptured cerebral aneurysms (n=264) who underwent endovascular coil embolization from January 2011 to June 2014. Thromboembolism occurred in 20 patients (7.4%), including 14 cases of ruptured aneurysms and 6 cases of unruptured aneurysms. The most common site of aneurysms was the anterior communicating artery (n=8), followed by middle cerebral artery (n=6). When we found an enlarged thromboembolism during coil embolization, we tried to dissolve it using tirofiban administered via IA and IV loading (5 μg/kg, respectively) for 3-5 minutes followed by IV maintenance (0.08 μg/kg/min) for approximately 4-24 hours. In 4 of 5 patients with total vessel occlusion, the vessel was recanalized to Thrombolysis in Cerebral Infarction Perfusion Scale (TICI) grade 3, and in 1 patient to TICI grade 2a. In 2 patients with partial vessel occlusion and 13 patients with minimal occlusion, the vessel recanalized to TICI grade 3. Irrelevant intracerebral hemorrhage was noted in 1 patient (5%), and thromboemboli-related cerebral infarction developed in 5 patients (25%), of which only 1 (5%) was symptomatic. IA/IV infusion and IV maintenance with tirofiban appear to be an effective rescue treatment for thromboembolism during endovascular coil embolization in patients with ruptured or unruptured cerebral aneurysms.

  13. 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

  14. Intravenous treprostinil infusion via a fully implantable pump for pulmonary arterial hypertension.

    PubMed

    Ewert, Ralf; Richter, Manuel J; Steringer-Mascherbauer, Regina; Grünig, Ekkehard; Lange, Tobias J; Opitz, Christian F; Warnke, Christian; Ghofrani, Hossein-Ardeschir

    2017-04-20

    Parenteral prostanoids infused via external pumps are well-established pulmonary arterial hypertension (PAH) treatments. However, local side-effects and systemic infections restrict their use. The purpose of this study was to investigate the safety of a fully implantable treprostinil infusion pump (LENUS Pro(®)) in patients with PAH. Thirty patients with PAH undergoing pump implantation (with stable PAH therapy for ≥3 weeks pre-implantation) were included in this prospective, multicenter, observational study (NCT01979822). Primary endpoints were predefined adverse events (AEs) during implantation, in-hospital and/or during 6-month follow-up. Refill-related AEs were a secondary endpoint. Twenty-nine patients completed 6-month follow-up (one underwent lung transplantation). During implantation, one pneumothorax (not requiring drainage) occurred. Four patients had an in-hospital AE (including one catheter revision). During 6-month follow-up, AEs were most frequent at the first refill (10); the most common AE was seroma around the pump. No infections occurred. One pump required replacement because of a defective septum caused by use of a non-approved refill needle (associated with extravasation). Apart from the extravasation, no refill-related AEs were recorded. Post hoc efficacy analyses showed significant improvements in functional class [number in functional class I/II/III/IV: 0/5/21/2 (baseline) versus 3/8/17/0 (6 months); p = 0.012] and 6-min walk distance (mean ± standard deviation: 407 ± 122 m versus 445 ± 127 m; n = 17; p = 0.014). This study supports use of a fully implantable treprostinil infusion pump in patients with PAH requiring parenteral prostanoids. Refills should be performed by specialized healthcare professionals at patients' homes or at experienced centers using approved equipment.

  15. A safe and effective dose of cisplatin in hepatic arterial infusion chemotherapy for hepatocellular carcinoma

    PubMed Central

    Osaki, Akihiko; Suda, Takeshi; Kamimura, Kenya; Tsuchiya, Atsunori; Tamura, Yasushi; Takamura, Masaaki; Igarashi, Masato; Kawai, Hirokazu; Yamagiwa, Satoshi; Aoyagi, Yutaka

    2013-01-01

    Cisplatin (CDDP) is an anticancer agent that is commonly used in hepatic arterial infusion (HAI) chemotherapy for hepatocellular carcinoma (HCC). This study aimed to clarify the safe and effective dose of CDDP in HAI for HCC. The hypervascular area was measured in 42 HCCs before and after HAI with CDDP. Serum platinum concentration was quantified in the peripheral and/or middle hepatic veins by atomic absorption spectrometry. The relation between the HCC response and CDDP dose was statistically analyzed. The multiple HCC nodules in an individual case generally demonstrated the same response to CDDP. The free-platinum concentration stayed relatively constant in the hepatic vein during HAI followed by a rapid decline, while total-platinum gradually increased then slowly disappeared over several days. After CDDP-HAI, 15 HCCs shrunk and 27 HCCs grew. The reduction rate in the shrunken nodules was tended to be correlated with CDDP dose after standardization with the target liver volume. On the other hand, the growth rate of the enlarged HCCs was significantly correlated with CDDP dose after normalization with creatinine clearance. These data support a recommendation of CDDP-HAI infusion where the amount of CDDP (mg) administered is less than patient creatinine clearance (mL/min/1.73 m2) upon an assumption of HCC doubling time of 90 days, and the targeted liver is smaller than 200 times the CDDP dose (mg). A further analysis is required to define appropriate injection speeds. PMID:24133631

  16. 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.

  17. Hepatic Arterial Infusion Chemotherapy Combined with Venous Embolization in a Patient with Hepatic Metastases with an Arteriovenous Shunt

    SciTech Connect

    Nishiofuku, Hideyuki; Tanaka, Toshihiro; Sakaguchi, Hiroshi; Yamamoto, Kiyosei; Inoue, Masayoshi; Sueyoshi, Satoru; Shinnkai, Takayuki; Hasegawa, Masatoshi; Kichikawa, Kimihiko

    2009-07-15

    We describe herein a patient who had hepatic metastases with an arteriovenous shunt and was treated by hepatic arterial infusion chemotherapy. The arteriovenous shunt was diagnosed by {sup 99m}Tc-macroaggregated albumin scintigraphy and hepatic venous embolization was performed to reduce shunt flow.

  18. 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.

  19. Hepatic arterial infusion chemotherapy for patients with huge unresectable hepatocellular carcinoma.

    PubMed

    Tsai, Wei-Lun; Lai, Kwok-Hung; Liang, Huei-Lung; Hsu, Ping-I; Chan, Hoi-Hung; Chen, Wen-Chi; Yu, Hsien-Chung; Tsay, Feng-Woei; Wang, Huay-Min; Tsai, Hung-Chih; Cheng, Jin-Shiung

    2014-01-01

    The optimal treatment for huge unresectable hepatocellular carcinoma (HCC) remains controversial. The outcome of transcatheter arterial chemoembolization (TACE) for patients huge unresectable HCC is generally poor and the survival benefit of TACE in these patients is unclear. The aim of the study is to compare the effect of hepatic arterial infusion chemotherapy (HAIC) versus symptomatic treatment in patients with huge unresectable HCC. Since 2000 to 2005, patients with huge (size >8 cm) unresectable HCC were enrolled. Fifty-eight patients received HAIC and 44 patients received symptomatic treatment. In the HAIC group, each patient received 2.4+1.4 (range: 1-6) courses of HAIC. Baseline characteristics and survival were compared between the HAIC and symptomatic treatment groups. The HAIC group and the symptomatic treatment group were similar in baseline characteristics and tumor stages. The overall survival rates at one and two years were 29% and 14% in the HAIC group and 7% and 5% in the symptomatic treatment group, respectively. The patients in the HAIC group had significantly better overall survival than the symptomatic treatment group (P<0.001). Multivariate analysis revealed that HAIC was the significant factor associated with the overall survival (relative risk: 0.321, 95% confidence interval: 0.200-0.515, P<0.001). None of the patients died due to immediate complications of HAIC. HAIC is a safe procedure and provides better survival than symptomatic treatment in patients with huge unresectable HCC.

  20. Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era.

    PubMed

    Ko, Y J; Karanicolas, P J

    2014-02-01

    Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy. In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.

  1. Comparison of Outcome of Hepatic Arterial Infusion Chemotherapy and Sorafenib in Patients with Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization.

    PubMed

    Hatooka, Masahiro; Kawaoka, Tomokazu; Aikata, Hiroshi; Morio, Kei; Kobayashi, Tomoki; Hiramatsu, Akira; Imamura, Michio; Kawakami, Yoshiiku; Murakami, Eisuke; Waki, Koji; Honda, Yoji; Mori, Nami; Takaki, Shintaro; Tsuji, Keiji; Kohno, Hirotaka; Kohno, Hiroshi; Moriya, Takashi; Nonaka, Michihiro; Hyogo, Hideyuki; Aisaka, Yasuyuki; Chayama, Kazuaki

    2016-07-01

    To compare the outcome of 5-fluorouracil (FU)-based hepatic arterial infusion chemotherapy (HAIC) with sorafenib monotherapy in patients with hepatocellular carcinoma (HCC) refractory to transcatheter arterial chemoembolization (TACE). In this retrospective cohort study, 123 patients with HCC refractory to TACE, with Child-Pugh A and free of extrahepatic metastasis, were divided into two groups: 65 received HAIC and 58 received sorafenib. Since the size of main tumor and portal vein invasion were significantly different between the HAIC and sorafenib groups, we selected 48 patients from the 65 patients of the HAIC group and 48 from the 58 patients of the sorafenib group. The model used one-to-one matching between the two groups using the case-control method matching method. The clinical characteristics of patients of the case-control HAIC (n=48) and sorafenib groups (n=48) were similar. Overall survival, time to progression and time to treatment failure (TTTF) were compared between the two groups. The median survival time and TTTF were significantly longer in the sorafenib group than in the HAIC group (15 and 12.2 months versus 8 and 4.4 months, respectively; p=0.021 and p=0.002, respectively). Multivariate analysis identified male gender (p=0.008), relative tumor size <50% (p=0.012), α-fetoprotein <400 ng/ml (p=0.005), and treatment with sorafenib (p=0.001) as significant and independent determinants of better overall survival. In patients with HCC refractory to TACE, overall survival was favorable in those treated with sorafenib rather than HAIC. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  2. 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.

  3. Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise thallium testing in the diagnosis of coronary artery disease

    SciTech Connect

    Coyne, E.P.; Belvedere, D.A.; Vande Streek, P.R.; Weiland, F.L.; Evans, R.B.; Spaccavento, L.J. )

    1991-05-01

    Adenosine is an endogenously produced compound that has significant effects as a coronary and systemic vasodilator. Previous studies suggest that intravenous infusion of adenosine, coupled with thallium-201 scintigraphy, may have specific value as a noninvasive means of evaluating coronary artery disease. The purpose of this study was to compare the diagnostic value of adenosine thallium testing with that of standard exercise thallium testing. One hundred subjects were studied with exercise thallium imaging and thallium imaging after adenosine infusion, including 47 with angiographically proved coronary artery disease and 53 control subjects. The overall sensitivity of the thallium procedures was 81% for the exercise study and 83% for the adenosine study (p = NS); the specificity was 74% for the exercise study and 75% for the adenosine study (p = NS). The diagnostic accuracy of the exercise study was 77% and that of the adenosine study was 79%. Ninety-four percent of subjects had an adverse effect due to the adenosine infusion; however, most of these effects were mild and well tolerated. All adverse effects abated within 30 to 45 s of the termination of the study, consistent with the very brief half-life of the agent. Thus, thallium-201 scintigraphy after intravenous infusion of adenosine has a diagnostic value similar to that of exercise thallium testing for evaluation of coronary artery disease. Adenosine thallium testing may be particularly useful in evaluating patients unable to perform treadmill exercise testing.

  4. Intra-carotid cold magnesium sulfate infusion induces selective cerebral hypothermia and neuroprotection in rats with transient middle cerebral artery occlusion.

    PubMed

    Song, Wei; Wu, Yong-Ming; Ji, Zhong; Ji, Ya-Bin; Wang, Sheng-Nan; Pan, Su-Yue

    2013-04-01

    Local hypothermia induced by intra-arterial infusion of cold saline reduces brain injury in ischemic stroke. Administration of magnesium sulfate through the internal carotid artery is also known to reduce ischemic brain damage. The neuroprotective effects of combination therapy with local endovascular hypothermia and intra-carotid magnesium sulfate infusion has not been evaluated. The aim of the study was to determine whether infusion of intra-carotid cold magnesium offers neuroprotective efficacy superior to cold saline infusion alone. Sixty-eight Sprague-Dawley rats were subjected to 3 h of middle cerebral artery occlusion and were randomly divided into six groups: sham-operated group; stroke control group; local cold magnesium infusion group; local cold saline infusion group; local normothermic magnesium infusion group; and local normothermic saline infusion group. Before reperfusion, ischemic rats received local infusion or no treatment. Infarct volume, neurological deficit, and brain water content were evaluated at 48 h after reperfusion. Selective brain hypothermia (33-34 °C) was successfully induced by intra-carotid cold infusion. Local cold saline infusion and local cold magnesium infusion reduced the infarct volumes by 48 % (p < 0.001) and 65 % (p < 0.001), respectively, compared with stroke controls. Brain water content was decreased significantly in animals treated with local cold magnesium infusion. Furthermore, the rats given a local cold magnesium infusion had the best neurological outcome. Local normothermic infusion failed to improve ischemic brain damage. These data suggest that local hypothermia induced by intra-carotid administration of cold magnesium is more effective in reducing acute ischemic damage than infusion of cold saline alone.

  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. Chemoembolization alone vs combined chemoembolization and hepatic arterial infusion chemotherapy in inoperable hepatocellular carcinoma patients

    PubMed Central

    Gao, Song; Zhang, Peng-Jun; Guo, Jian-Hai; Chen, Hui; Xu, Hai-Feng; Liu, Peng; Yang, Ren-Jie; Zhu, Xu

    2015-01-01

    AIM: To compare the efficacy and safety of chemoembolization alone or chemoembolization combined with hepatic arterial infusion chemotherapy (HAIC), including oxaliplatin (OXA), 5-fluorouracil (5-FU) and folinic acid (CF), in inoperable hepatocellular carcinoma (HCC) without distant metastasis. METHODS: Eighty-four inoperable HCC patients were enrolled. Thirty-nine patients underwent chemoembolization alone, and the other 45 patients underwent chemoembolization + HAIC (OXA/5-FU/CF) treatment non-randomly. The progression free survival (PFS), objective response rate (ORR), disease control rate (DCR) and adverse reactions were compared between the two groups. RESULTS: A significant difference in the ORR was observed between the chemoembolization alone and chemoembolization + HAIC groups. There was no statistically significant difference in DCR between the two groups. The median PFS (mPFS) showed a significant difference between the two groups. For patients with BCLC stage A/B disease, with or without vessel invasion, the chemoembolization + HAIC group showed better mPFS when compared to chemoembolization alone, but no significant difference was found in patients with BCLC stage C disease. The parameter of pain (grade III-IV) in the chemoembolization + HAIC group was increased statistically. CONCLUSION: Chemoembolization combined with HAIC with OXA/5-FU/CF may be safe and more effective than chemoembolization alone for inoperable HCC patients without distant metastasis. PMID:26420971

  8. Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement.

    PubMed

    Karanicolas, P J; Metrakos, P; Chan, K; Asmis, T; Chen, E; Kingham, T P; Kemeny, N; Porter, G; Fields, R C; Pingpank, J; Dixon, E; Wei, A; Cleary, S; Zogopoulos, G; Dey, C; D'Angelica, M; Fong, Y; Dowden, S; Ko, Y J

    2014-02-01

    Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip.

  9. Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement

    PubMed Central

    Karanicolas, P.J.; Metrakos, P.; Chan, K.; Asmis, T.; Chen, E.; Kingham, T.P.; Kemeny, N.; Porter, G.; Fields, R.C.; Pingpank, J.; Dixon, E.; Wei, A.; Cleary, S.; Zogopoulos, G.; Dey, C.; D’Angelica, M.; Fong, Y.; Dowden, S.; Ko, Y.J.

    2014-01-01

    Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip PMID:24523610

  10. 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.

  11. Combined therapy of transcatheter hepatic arterial embolization with intratumoral dendritic cell infusion for hepatocellular carcinoma: clinical safety

    PubMed Central

    Nakamoto, Y; Mizukoshi, E; Tsuji, H; Sakai, Y; Kitahara, M; Arai, K; Yamashita, T; Yokoyama, K; Mukaida, N; Matsushima, K; Matsui, O; Kaneko, S

    2007-01-01

    The curative treatments for hepatocellular carcinoma (HCC), including surgical resection and radiofrequency ablation (RFA), do not prevent tumour recurrence effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute to the eradication of the residual and recurrent tumour cells. The current study was designed to assess the safety and bioactivity of DC infusion into tumour tissues following transcatheter hepatic arterial embolization (TAE) for patients with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were differentiated into phenotypically confirmed DCs. Ten patients were administered autologous DCs through an arterial catheter during TAE treatment. Shortly thereafter, some HCC nodules were treated additionally to achieve the curative local therapeutic effects. There was no clinical or serological evidence of adverse events, including hepatic failure or autoimmune responses in any patients, in addition to those due to TAE. Following the infusion of 111Indium-labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17 days, and were associated with lymphocyte and monocyte infiltration. Interestingly, T lymphocyte responses were induced against peptides derived from the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion in some patients. The cumulative survival rates were not significantly changed by this strategy. These results demonstrate that transcatheter arterial DC infusion into tumour tissues following TAE treatment is feasible and safe for patients with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC infusion may induce immune responses to unprimed tumour antigens, providing a plausible strategy to enhance tumour immunity. PMID:17223971

  12. 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

  13. Clinical interrogation and application of super-selective intracranial artery infusion chemotherapy for lung cancer patients with brain metastases.

    PubMed

    Rong, J; Chunhua, M; Yuan, L; Ning, M; Jinduo, L; Bin, W; Liwei, S

    2015-11-01

    The purpose of this study was to evaluate the clinical efficacy of super-selective intracranial artery infusion chemotherapy and to determine correlated prognostic parameters for advanced lung cancer patients with brain metastases. Fifty-four lung cancer patients with brain metastasis who had no previous treatment were enrolled for the study. These patients received super-selective intracranial artery infusion chemotherapy, as well as arterial infusion chemotherapy for primary and metastatic lesions. The procedure was performed once every 4 weeks. Patients were monitored to evaluate short-term clinical outcomes 4 weeks after the first 2 treatments, and follow-up visits performed every 4 weeks after the first 4 treatments until the appearance of disease progression or intolerable toxicity. All 54 cases were treated at least 4 times. The overall response rate was 55.56% (30/54), and the disease control rate was 85.19% (46/54). The median overall survival was 7 months, with a 95% confidence interval (CI) of 5.87-8.13 months, and the median progression-free survival was 4 months, with a 95% CI of 3.20-4.80 months. The 6-month survival rate and 1-year survival rate were 81.48% (44/54) and 18.52% (10/54), respectively. Super-selective intracranial artery infusion chemotherapy provides a clinically efficacious avenue of treatment for lung cancer patients with brain metastases. Pathological classification, Karnofsky performance status, and extracranial metastases may serve as reliable prognostic parameters in determining the clinical outcomes for lung cancer patients with brain metastases.

  14. [Maxillary Cancer with Metastasis to the Rouviere Nodes -- Complete Response to Chemoradiotherapy Using a Selective Intra-Arterial Infusion Technique].

    PubMed

    Yamashiro, Keita; Heianna, Joichi; Azama, Kimei; Iraha, Yuko; Yamashiro, Tsuneo; Kinoshita, Ryo; Toita, Takafumi; Toyama, Masatomo; Agena, Shinya; Maeda, Hiroyuki; Suzuki, Mikio; Murayama, Sadayuki

    2016-02-01

    We report a case of advanced maxillary cancer with multiple lymph node metastases, including metastasis to the Rouviere nodes, which were successfully treated with chemoradiotherapy using a selective intra-arterial infusion technique.A 71-yearold man presented to our hospital with complaints of a staggering gait and epistaxis.He was diagnosed with maxillary cancer (squamous cell carcinoma)classified as T4a disease.Because multiple lymph node metastases were detected, including metastasis to the Rouviere nodes, radical surgical treatment was considered inadequate.Thus, the patient was treated with concurrent chemoradiotherapy with selective intra-arterial infusion of nedaplatin and docetaxel.After chemoradiotherapy, the maxillary cancer and lymph metastasis nearly resolved and the patient achieved a complete response.No additional surgery was needed, and the patient was discharged.We suggest that chemoradiotherapy using a selective intra-arterial infusion technique is a highly effective treatment option for patients with maxillary cancer and metastasis to the Rouviere nodes.

  15. Hepatic Arterial Infusion Chemotherapy for Unresectable Liver Metastases of Colorectal Cancer: A Multicenter Retrospective Study.

    PubMed

    Lim, Annie; Le Sourd, Samuel; Senellart, Hélène; Luet, Dominique; Douane, Frédéric; Perret, Christophe; Bouvier, Antoine; Métairie, Sylvie; Cauchin, Estelle; Rougier, Philippe; Matysiak-Budnik, Tamara; Touchefeu, Yann

    2017-03-14

    Hepatic arterial infusion chemotherapy (HAIC) is a treatment used for liver metastases (LM) of colorectal cancer (CRC). Because of its technical conditions, it has been used in only a few experienced centers in France. Our aim was to evaluate its feasibility, efficacy and tolerance in 4 centers. Clinical, biological, and radiological data of patients treated with HAIC for unresectable LM from CRC in 4 institutions from October 2011 to January 2016 were retrospectively analyzed. Sixty-one patients with unresectable LM from CRC were included. Patients had previously received systemic chemotherapy in 95% of patients and 82.8% had previous oxaliplatin treatment. Oxaliplatin was administered using an intra-arterial route combined with intravenous (I.V.) Five-fluorouracil (5-FU) with leucovorin alone in 43.3% of patients, or combined with other I.V. chemotherapies or monoclonal antibodies in 56.7% of patients. Grade 3 to 4 clinical toxicities were reported in 16% of patients, including 9.8% of neurotoxicity, and Grade 3 to 4 biological toxicities were reported in 24.6% of patients including 22.2% with neutropenia. Catheter-related complications were observed in 31.1%. Tumor response rate in first- and second-line was 26.5% and third- and fourth-line was 11%. Median overall survival (OS) in first- and second-line was 13.5 months and third- and fourth-line was 8.3 months (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.39-1.12; P = .1729). Median progression-free survival (PFS) in first- and second-line was 9 months and third- and fourth-line were 6 months (HR, 0.53; 95% CI, 0.18-0.659; P = .0037). A secondary R0 resection was possible in 10 cases (16.4%) allowing a 2-year survival of 80%. These data confirm that in centers that recently developed HAIC using oxaliplatin, this treatment is feasible and has acceptable tolerance. The results, in terms of hepatic PFS, PFS, OS, and the rate of secondary resections of LM, are in the range of published data, and they

  16. Intra-arterial Tirofiban Infusion for Partial Recanalization with Stagnant Flow in Hyperacute Cerebral Ischemic Stroke

    PubMed Central

    Baik, S.K.; Oh, S.J.; Park, K-P.; Lee, J-H.

    2011-01-01

    Summary Early reocclusion is a major concern associated with poor clinical outcomes in patients with an ischemic cerebral stroke. This occurs most frequently in patients with partial initial recanalization. This study focuses on partial recanalization with stagnant antegrade flow after intravenous (IV) tPA or spontaneously, treated with the administration of intra-arterial (IA) tirofiban. Three patients with initial M1 occlusion on diagnostic studies had an occluded segment that was recanalized with stagnant flow after IV tPA or spontaneously. In all cases, IA tirofiban was administrated. We evaluated the distal blood flow and the degree of vascular narrowing in the pre and post-procedure angiography and at follow-up in addition to the clinical status. In all patients, severe vascular narrowing with stagnation of blood flow was detected in the initial M1. After infusion of IA tirofiban, improvement of the distal blood flow was achieved rapidly within 40 minutes in all patients. The severe vascular narrowing resolved rapidly in two patients without residual stenosis. In one patient, moderate vascular narrowing was still present. The median baseline National Institutes of Health Stroke Scale (NIHSS) scores were 18 and the median post-procedural NIHSS scores were 2 at two weeks. No intracerebral hemorrhage occurred in any of the patients. Treatment with IA tirofiban was safe and effective in patients with partial initial recanalization. It can be suggested that detection of any partial recanalization is time for administration of glycoprotein IIb-IIIa receptor inhibitor in hyperacute ischemic stroke. PMID:22192548

  17. Robotic assisted placement of hepatic artery infusion pump is a safe and feasible approach.

    PubMed

    Dhir, Mashaal; Zenati, Mazen S; Padussis, James C; Jones, Heather L; Perkins, Samantha; Clifford, Amber K; Steve, Jennifer; Hogg, Melissa E; Choudry, Haroon A; Holtzman, Matthew P; Zeh, Herbert J; Pingpank, James F; Bartlett, David L; Zureikat, Amer H

    2016-09-01

    Hepatic artery infusion (HAI) chemotherapy can be combined with systemic chemotherapy for the treatment of isolated unresectable colorectal liver metastases (IU-CRLM) and intrahepatic cholangiocarcinoma (U-ICC). However, HAI pump placement requires a major laparotomy that may be associated with morbidity. We hypothesized that the computer-assisted robotic platform would be well suited for this procedure and report the first single institutional case series of robotic assisted HAI pump placement for primary and secondary malignancies of the liver. A retrospective review of patients who underwent robotic assisted HAI pump placement from January 2008 to January 2016. Peri-operative outcomes were evaluated. A total of 24 consecutive patients underwent robotic assisted HAI pump placement. Median age was 61 years and 50% were females. Main indications were colorectal cancer = 17 (71%) and intrahepatic cholangiocarcinoma = 4 (17%). The majority (87.5%) of patients had bilobar disease with a median of 6 liver lesions. Concurrent procedures including ablation +/- resection and colectomies were performed in 58% of the patients. Median operative time was 282 min, with median blood loss of 100 ml and length of stay 6 days. Conversion to open was required in one (4%) case. Grade 3 or higher complications were seen in 13% of cases and pump related complications were seen in 21% of patients. All except one HAI pumps could be used for pump chemotherapy. CUSUM analysis of operative time indicated a learning curve of eight cases. Robotic assisted placement of HAI pump placement is safe, feasible, and obviates the need for major laparotomy. J. Surg. Oncol. 2016;114:342-347. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Hepatic artery infusion with raltitrexed or 5-fluorouracil for colorectal cancer liver metastasis

    PubMed Central

    Guo, Jian-Hai; Zhang, Hang-Yu; Gao, Song; Zhang, Peng-Jun; Li, Xiao-Ting; Chen, Hui; Wang, Xiao-Dong; Zhu, Xu

    2017-01-01

    AIM To evaluate the efficiency and safety of hepatic artery infusion chemotherapy (HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer (CRC) liver metastasis (CRCLM). METHODS A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed. RESULTS The median survival time (MST) from diagnosis of CRC was 40.8 mo in the oxaliplatin plus raltitrexed (TOMOX) arm and 33.5 mo in the oxaliplatin plus 5-fluorouracil (FOLFOX) arm (P = 0.802). MST from first HAIC was 20.6 mo in the TOMOX arm and 15.4 mo in the FOLFOX arm (P = 0.734). Median progression-free survival (PFS) from first HAIC was 4.9 mo and 6.6 mo, respectively, in the TOMOX arm and FOLFOX arm (P = 0.215). Leukopenia (P = 0.026) was more common in the FOLFOX arm, and hepatic disorder (P = 0.039) was more common in the TOMOX arm. There were no treatment-related deaths in the TOMOX arm and one treatment-related death in the FOLFOX arm. Analysis of prognostic factors indicated that response to HAIC was a significant factor related to survival. CONCLUSION No significant difference in survival was observed between the TOMOX and FOLFOX arms. HAIC treatment with either TOMOX or FOLFOX was demonstrated as an efficient and safe alternative choice. PMID:28293087

  19. Insulin Infusion on Postoperative Complications of Coronary Artery Bypass Graft in Patients With Diabetes Mellitus

    PubMed Central

    Masoumi, Gholamreza; Frasatkhish, Rasoul; Bigdelian, Hamid; Ziyaefard, Mohsen; Sadeghpour-Tabae, Ali; Mansouri, Mojtaba; Jalali, Alireza

    2014-01-01

    Background: Cardiovascular events are common in patients with diabetes mellitus (DM), which make coronary artery bypass graft (CABG) a highly demanded surgery in this population. Tight control of blood glucose in patients with DM is beneficial in reducing postoperative complications; however, the adequate range has not been determined yet. Objectives: This study aimed to investigate the effect of semi-tight (moderate) control of DM on complications and serum glucose levels during and after CABG. Patients and Methods: In this prospective clinical trial, 18 and 31 patients with and without DM, respectively, who were referred to Shahid Chamran Hospital, Isfahan, Iran, for elective CABG surgery, were enrolled. For DM group, patients with controlled DM (i.e. glycosylated hemoglobin levels [HgA1C] ≤ 7%) were recruited. Blood glucose level (blood sugar, BS) was measured after anesthesia, during pumping, warming, off pumping, six and 12 hours after Intensive Care Unit (ICU) admission, and at discharging from the hospital. The hemodynamic state of the patients, bleeding, need of blood transfusion, infection, and duration of hospitalization were also monitored and recorded. Results: None of the BS measurements (FBS, after anesthesia, on-pump, warming, off pump, six and 12 hours after ICU admission, and at discharge) were significantly different between study groups (P > 0.05). Frequency of surgery site bleeding and blood transfusion need were not significantly different between these groups (P > 0.05). Conclusions: Semi-tight control of DM with insulin infusion during operation did not led to any difference in the type and rate of CABG complications between patients with well-controlled and those without DM; however, BS levels in patients with well-controlled DM could be more easily controlled. PMID:25478540

  20. 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

  1. 5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved.

    PubMed

    Davis, Robert Patrick; Pattison, Jill; Thompson, Janice M; Tiniakov, Ruslan; Scrogin, Karie E; Watts, Stephanie W

    2012-05-06

    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.

  2. Main complications and results of treatment with intra-arterial infusion chemotherapy through the subclavian and thoracic arteries for locally advanced breast cancer.

    PubMed

    Wang, Xiaoyi; Gan, Changing; Li, Hongyuan; Wei, Yuxian; Zhu, Donchang; Yang, Guanglun; Su, Xinliang; Rodier, Jean-François; Ren, Guosheng

    2013-07-01

    Intra-arterial infusion chemotherapy for locally advanced breast cancer (LABC) has been previously performed. However, the main complications of this type of chemotherapy remain to be clarified. In the present study, catheterization chemotherapy was carried out for 53 LABC cases (stage IIIa-IIIc) between May, 2006 and March, 2007. For IIIB and IIIC patients, the catheters were guided to the opening of the subclavian artery. For stage IIIa patients, the catheters were placed into the thoracic artery through a subcutaneous femoral artery puncture. One to four cycles of chemotherapy (mean, 1.6 cycles) were administered for the patients using taxotere, epidoxorubicin, 5-fluorouracil and/or cyclophosphamide. The interval time between the two cycles was 21 days. Seven cases were identified as complete response (CR, 13.2%), 41 cases were partial response (PR, 77.4%) with a rate of effectiveness of (CR + PR, 90.6%), 5 cases were stable disease (SD, 9.40%) and no case was progressive. Pain of the ipsilateral upper extremity was present in 7 cases. Two cases exhibited ipsilateral upper extremity atrophy following drug administration from the opening of the subclavian artery. One case experienced neck pain and headache, while in one case necrosis of local skin was evident. Hematological toxicity over grade 3 was observed in 6 cases (11.30%). Systemic toxicity was mild and did not affect the quality of life of the patients. Overall survival was identified as 18/51 (35.3%), and free-disease survival as 10/51 (19.6%). In conclusion, intra-arterial infusion chemotherapy is an effective local control treatment for LABC. The main complications are pain of the ipsilateral upper extremity and neck as well as headache. Severe complications are ipsilateral upper extremity atrophy and necrosis of local skin. During the treatment, controlling the pressure of the tourniquet and velocity of drug administration are crucial for reducing local complications.

  3. Main complications and results of treatment with intra-arterial infusion chemotherapy through the subclavian and thoracic arteries for locally advanced breast cancer

    PubMed Central

    WANG, XIAOYI; GAN, CHANGING; LI, HONGYUAN; WEI, YUXIAN; ZHU, DONCHANG; YANG, GUANGLUN; SU, XINLIANG; RODIER, JEAN-FRANÇOIS; REN, GUOSHENG

    2013-01-01

    Intra-arterial infusion chemotherapy for locally advanced breast cancer (LABC) has been previously performed. However, the main complications of this type of chemotherapy remain to be clarified. In the present study, catheterization chemotherapy was carried out for 53 LABC cases (stage IIIa–IIIc) between May, 2006 and March, 2007. For IIIB and IIIC patients, the catheters were guided to the opening of the subclavian artery. For stage IIIa patients, the catheters were placed into the thoracic artery through a subcutaneous femoral artery puncture. One to four cycles of chemotherapy (mean, 1.6 cycles) were administered for the patients using taxotere, epidoxorubicin, 5-fluorouracil and/or cyclophosphamide. The interval time between the two cycles was 21 days. Seven cases were identified as complete response (CR, 13.2%), 41 cases were partial response (PR, 77.4%) with a rate of effectiveness of (CR + PR, 90.6%), 5 cases were stable disease (SD, 9.40%) and no case was progressive. Pain of the ipsilateral upper extremity was present in 7 cases. Two cases exhibited ipsilateral upper extremity atrophy following drug administration from the opening of the subclavian artery. One case experienced neck pain and headache, while in one case necrosis of local skin was evident. Hematological toxicity over grade 3 was observed in 6 cases (11.30%). Systemic toxicity was mild and did not affect the quality of life of the patients. Overall survival was identified as 18/51 (35.3%), and free-disease survival as 10/51 (19.6%). In conclusion, intra-arterial infusion chemotherapy is an effective local control treatment for LABC. The main complications are pain of the ipsilateral upper extremity and neck as well as headache. Severe complications are ipsilateral upper extremity atrophy and necrosis of local skin. During the treatment, controlling the pressure of the tourniquet and velocity of drug administration are crucial for reducing local complications. PMID:24649239

  4. Evaluation of myocardial viability with thallium-201 infusion MPSPECT after oral glucose application in patients with chronic coronary artery disease.

    PubMed

    Hasbek, Zekiye; Turgut, Bulent; Erselcan, Taner; Yalta, Kenan; Tandogan, Izzet; Ozer, Gurkan; Ozdemir, Umit; Turgut, Nergiz Hacer

    2009-10-01

    The aim of this study was to evaluate the myocardial viability in nondiabetic patients with chronic coronary artery disease (CCAD) or past myocardial infarction (MI), using thallium-201 infusion myocardial perfusion single-photon emission computed tomography (MPSPECT) imaging after oral glucose application (Glu+Tl-infusion). In this study, 33 nondiabetic patients (three female, 30 male, mean age: 55.24+/-11 years, range: 33-77 years) with MI history or known CCAD were included. Rest/redistribution/24 h-late-MPSPECT imaging was performed for all patients. In all patients in whom fixed perfusion defect was observed on any wall of the left ventriculi, after 24 h-late-MPSPECT imaging, 75 g oral glucose was given. Thirty minutes later, 1 mCi thallium-201 in 100 ml of physiological saline solution was applied in a period of 20 min by slow infusion. After infusion at the 10th minute, MPSPECT imaging was performed. Perfusion was evaluated visually for a total of 3432 segments with the 26-segment 5-point scoring technique. Scoring measured perfusion as 0 = no perfusion defect, 1 = mildly reduced, 2 = moderately reduced, 3 = severely reduced, and 4 = absent uptake. Scores '0 and 1' were considered normal and scores '2-4' were considered abnormal. For serum insulin levels measured after glucose application, a significant increase was determined, according to the period before glucose application (P<0.001). When compared with rest MPSPECT images, segmental perfusion improvement both in redistribution and in the 24 h-late-MPSPECT images were 16.3 and 18.3%, respectively. This ratio was found to be 27.2% for Glu+Tl-infusion images. The ratios of segments in which perfusion was worsening were calculated to be 9.4, 14.5, and 7.3%, respectively, for redistribution, 24 h-late-MPSPECT, and Glu+Tl-infusion images. When this evaluation was made for all three vessel areas, again the highest perfusion improvement and the lowest perfusion worsening were detected for Glu+Tl-infusion images

  5. 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

  6. Therapeutic time window of hypothermia is broader than cerebral artery flushing in carotid saline infusion after transient focal ischemic stroke in rats.

    PubMed

    Ji, Yabin; Hu, Yafang; Wu, Yongming; Ji, Zhong; Song, Wei; Wang, Shengnan; Pan, Suyue

    2012-09-01

    Intracarotid cold saline infusion (ICSI) protects against ischemic stroke not only due to the resulting hypothermia, but also as a result of the cerebral artery flushing. To assess the relative benefit of hypothermia and cerebral artery flushing in neuroprotection, hypothermic and normothermic saline infusions were administrated over a serial time points after the initiation of reperfusion in a rat ischemia model. Ischemic strokes were induced in Sprague-Dawley rats (n = 115) by occluding the middle cerebral artery for 2 hours using an intraluminal filament. In the hypothermic groups, the brain temperature was lowered to 33-34°C for 20 minutes by ICSI at three time points (0, 1, and 2 hours) after reperfusion. Correspondingly, in the normothermic groups, the brain temperature was maintained at normal levels during intracarotid normothermic saline infusion (INSI) for 20 minutes at the same time points. After 48-hour reperfusion, infarct sizes and brain water contents were determined using 2,3,5-triphenyltetrazolium chloride (TTC) staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100beta, and matrix metalloproteinase 9 (MMP9) in the serum were measured by enzyme-linked immunoassay (ELISA). Neurological deficits were also evaluated. Immediate infusion after the onset of reperfusion (0 hour) did not result in significant difference for reductions of infarct sizes, neurological deficits or S100beta serum levels between ICSI and INSI groups, compared with the non-infusion group. However, brain water content and NSE serum level were significantly lower in the ICSI group than the non-infusion group. When the infusions were started 1 hour after reperfusion, both ICSI and INSI infusions still reduced the infarct sizes, but only ICSI significantly decreased the brain water content, neurological deficits and S100beta serum level. All therapeutic effects of INSI disappeared when infusions were started 2 hours after reperfusion

  7. Development of a New Subclavian Arterial Infusion Chemotherapy Method for Locally or Recurrent Advanced Breast Cancer Using an Implanted Catheter-Port System After Redistribution of Arterial Tumor Supply

    SciTech Connect

    Takizawa, Kenji Shimamoto, Hiroshi Ogawa, Yukihisa Yoshimatsu, Misako Yagihashi, Kunihiro Nakajima, Yasuo; Kitanosono, Takashi

    2009-09-15

    Locally or recurrent advanced breast cancers can receive arterial blood supply from various arteries, such as the internal thoracic artery (ITA), the lateral thoracic artery, and the other small arterial branches originating from the subclavian artery. Failure to catheterize and subsequent formation of collateral arterial blood supply from various arteries are some of the reasons why the response to conventional selective transarterial infusion chemotherapy is limited and variable. To overcome this problem, we developed a new subclavian arterial infusion chemotherapy method using an implanted catheter-port system after redistribution of arterial tumor blood supply by embolizing the ITA. We named this technique ('redistributed subclavian arterial infusion chemotherapy' (RESAIC)). Using RESAIC, patients can be treated on an outpatient basis for extended periods of time. Eleven patients underwent RESAIC, and the complete remission and partial response rate in 10 evaluable patients was 90%: complete remission [CR] n = 4, partial remission n = 4, stable disease n = 1, and not evaluable n = 1. Three of four patients with CR had no distant metastasis, and modified radical mastectomy was performed 1 month after conclusion of RESAIC. The resected specimens showed no residual cancer cells, and pathologically confirmed complete remission was diagnosed in each of these cases. Although temporary grade-3 myelosuppression was seen in three patients who were previously treated by systemic chemotherapy, there was no other drug-induced toxicity or procedure-related complications. RESAIC produced a better response and showed no major complications compared with other studies despite the advanced stage of the cancers.

  8. 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.

  9. 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

  10. Urokinase therapy in neonates with catheter related central venous thrombosis.

    PubMed

    Wever, M L; Liem, K D; Geven, W B; Tanke, R B

    1995-02-01

    The results of fibrinolytic therapy with urokinase were evaluated in 26 neonates with catheter related central venous thrombosis. Complete thrombolysis could be achieved in 13 patients (50%), partial thrombolysis in 3 patients (12%). No effect was seen in 10 patients (38%). Therapy success was influenced by age, size and location of the thrombus. Coincidence of infection occurred in 16 patients (62%). Mild hemorrhagic complications were seen in 2 patients (8%), no other significant side effects were observed. Nine patients with residual thrombosis were treated with oral anticoagulants following urokinase resulting in resolution of the thrombus in 6 patients within 3 months (67%). The incidence of asymptomatic recurrent thrombosis was high (28%). Urokinase might be an effective and safe treatment for central venous thrombosis in neonates. Prophylactic antibiotic therapy during the infusion of urokinase and long-term treatment with oral anticoagulants after thrombosis are advisable. Early detection of thrombosis might enhance the success rate of fibrinolytic therapy. Therefore, we strongly recommend routine echocardiographic screening of central venous catheters.

  11. Continuous Regional Arterial Infusion of Protease Inhibitors Has No Efficacy in the Treatment of Severe Acute Pancreatitis

    PubMed Central

    Horibe, Masayasu; Sasaki, Mitsuhito; Sanui, Masamitsu; Sugiyama, Daisuke; Iwasaki, Eisuke; Yamagishi, Yoshiyuki; Sawano, Hirotaka; Goto, Takashi; Ikeura, Tsukasa; Hamada, Tsuyoshi; Oda, Takuya; Yasuda, Hideto; Shinomiya, Wataru; Miyazaki, Dai; Hirose, Kaoru; Kitamura, Katsuya; Chiba, Nobutaka; Ozaki, Tetsu; Yamashita, Takahiro; Koinuma, Toshitaka; Oshima, Taku; Yamamoto, Tomonori; Hirota, Morihisa; Moriya, Takashi; Shirai, Kunihiro; Mayumi, Toshihiko; Kanai, Takanori

    2017-01-01

    Objective The aim of this study is to assess the effectiveness of continuous regional arterial infusion (CRAI) of protease inhibitors in patients with severe acute pancreatitis (SAP) including acute necrotizing pancreatitis. Methods This retrospective study was conducted among 44 institutions in Japan from 2009 to 2013. Patients 18 years or older diagnosed with SAP according to the criteria of the Japanese Ministry of Health, Labour and Welfare study group (2008) were consecutively enrolled. We evaluated the association between CRAI of protease inhibitors and mortality, incidence of infection, and the need for surgical intervention using multivariable logistic regression analysis. Results Of 1159 patients admitted, 1097 patients with all required data were included for analysis. Three hundred and seventy-four (34.1%) patients underwent CRAI of protease inhibitors and 723 (65.9%) did not. In multivariable analysis, CRAI of protease inhibitors was not associated with a reduction in mortality, infection rate, or need for surgical intervention (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.47–1.32, P = 0.36; OR 0.97, 95% CI 0.61–1.54, P = 0.89; OR 0.76, 95% CI 0.50–1.15, P = 0.19; respectively). Conclusions Continuous regional arterial infusion of protease inhibitors was not efficacious in the treatment of patients with SAP. PMID:27977624

  12. [A case of double cancer of gastric and hepatocellular carcinoma associated with cirrhosis treated by hepatic resection after intra-hepatic arterial infusion chemotherapy].

    PubMed

    Une, Y; Nagabuchi, E; Ogasawara, K; Kamiyama, T; Sato, Y; Kawamukai, Y; Sato, N; Nakajima, Y; Uchino, J

    1990-08-01

    A case of double cancer, early gastric cancer and hepatocellular carcinoma, was reported. The patient was diabetic and had liver cirrhosis. After gastrectomy for gastric cancer which was hemorrhagic, he was treated by intra-hepatic arterial infusion chemotherapy followed by hepatic resection. Histopathologically, about half of the main tumor showed necrosis, but very viable new cancer cell nests were seen around the main nodule. The patient is in good condition without recurrence of hepatic lesion 1 year after resection. The usefulness of arterial infusion chemotherapy was demonstrated in the case of double cancer, in which it is difficult to resect both cancers simultaneously.

  13. Hepatic arterial infusion chemotherapy with a coaxial reservoir system using a non-braided spiral tip microcatheter.

    PubMed

    Koganemaru, Masamichi; Abe, Toshi; Iwamoto, Ryoji; Nonoshita, Masaaki; Yoshida, Seigo; Uchiyama, Daiji; Hayabuchi, Naofumi

    2012-01-01

    To evaluate the efficacy and safety of a coaxial reservoir system with a non-braided spiral tip microcatheter and exclusive port for hepatic arterial infusion chemotherapy. In vitro evaluation included evaluation of pressure tolerance/flow rate of the coaxial reservoir system, and the strength of connection between the 2.7-F catheter and port. Due to the difficulty of implanting conventional reservoirs, coaxial reservoirs were implanted via the femoral artery of 80 patients. We implanted a non-braided 2.7-F microcatheter with a spiral shaped tip, 5-F catheter, and a port. Clinical assessment included evaluation of technical success and complications. In vitro evaluation of the coaxial reservoir at its maximum pressure load showed that flow rates for 300 mg I/mL iopamidol contrast medium were 0.25 ± 0.04 mL/s (undiluted), 1.03 ± 0.01 mL/s (50% dilution), and 2.91 ± 0.01 mL/s (30% dilution). Connection strength between the 2.7-F catheter and port was 13.4 ± 0.57 N. Percutaneous port catheter placement was successful in all patients (100%, n = 80). Complications included hepatic arterial occlusion (10%, n = 8), catheter tip dislocation (1.3%, n = 1), and catheter occlusion (1.3%, n = 1). A coaxial reservoir system with a non-braided microcatheter and exclusive port is safe and effective for difficulty of implanting conventional reservoir.

  14. [Superselective intra-arterial infusion therapy with docetaxel, cisplatin and 5-fluorouracil for head and neck cancer--for tongue cancer patients in comparison patients with other therapies].

    PubMed

    Furusaka, Tohru

    2006-09-01

    In order to cure head and neck cancer without resection, chemotherapy (superselective intra-arterial infusion therapy with DCF) was conducted by anterograde, superselective intra-arterial infusion of 50-60 mg/m(2) of DOC and 50-60 mg/m(2) of CDDP via the femoral artery on day 1 followed by continuous intravenous instillation of 600-750 mg/m(2)/day of 5-FU for 5 days from day 2. A total of 70 patients with advanced and recurrent cancer of the head and neck have been treated since April 2000. With the median follow-up duration of 1,017 days, the survival rate was 92.7% and the organ preservation rate was 90.1%. Almost no complications associated with this therapy were observed. Due to space limitations, here we report only cases of tongue cancer. Histological CR was obtained from all 19 patients with squamous cell cancer of the tongue. With the median follow-up duration of 1,371 days (45.7 months: 471-2, 133 days), the survival rate was 94.74% and the organ preservation rate was 88.42% by the Kaplan-Meier method. For both the survival rate and organ preservation rate, extremely good results were obtained by the superselective intra-arterial infusion therapy with DCF compared to the intravenous infusion therapy using a combination of CDDP and 5-FU (five-year survival rate: 20%) as well as the superselective intra-arterial infusion of CDDP alone followed by continuous intravenous infusion of 5-FU (five year survival rate: 28.5%) that had been conducted before. Major adverse effects observed were leukopenia and alopecia. Although patients who underwent concurrent radiation therapy developed mucositis and dermatitis, both were reversible changes.

  15. [Intrathoracic washing with urokinase was effective for empyema with atelectasis].

    PubMed

    Fujiwara, Kiyohiro; Kobayashi, Shinya; Fujioka, Nobuhiro; Teramoto, Kanako; Itoh, Takefumi; Sugimura, Hiroko; Takezawa, Yuichi

    2013-05-01

    A 60-year-old man had a medical examination because of fever in the emergency hospital and had a diagnosis of pneumonia and was treated, but he was admitted to our hospital 2 days later because there was not the improvement of his symptom. The chest computed tomography(CT)image showed multilocular pleural effusions and lower lobe atelectasis with the air bronchogram on the left side. We diagnosed the case as empyema and inserted a catheter, but drainage was very few and injected 60,000 urokinase units for 3 days from the next day. We removed a drain 2 days after the 3rd infusion, and the pleural thickening became mild, and atelectasis was gradually improved in the chest CT image, and the inflammatory reaction was reduced, too. The intrathoracic washing with urokinase was thought to be effective for empyema with atelectasis.

  16. Activity of urokinase diluted in 0.9% sodium chloride injection or 5% dextrose injection and stored in glass or plastic syringes.

    PubMed

    Patel, J P; Tran, L T; Sinai, W J; Carr, L J

    1991-07-01

    The effects of the diluent, the container, the i.v. set, and the drug concentration on the adsorption of urokinase to i.v. administration systems were studied, along with the compatibility of urokinase with plastic and glass syringes. Solutions of urokinase 1500 and 5000 IU/mL in 0.9% sodium chloride injection and 5% dextrose injection in glass and polyvinyl chloride (PVC) containers were sampled at 2 and 30 minutes. Administration sets were attached to PVC containers containing the urokinase-5% dextrose injection solutions, and samples were collected at 90 and 150 minutes. Glass and polypropylene syringes containing urokinase 5000 IU/mL in 0.9% sodium chloride injection or 5% dextrose injection were sampled at 0, 4, 8, and 24 hours. Urokinase activity was measured by an in vitro clot lysis assay. No urokinase diluted in 0.9% sodium chloride injection adsorbed to glass or PVC containers. For urokinase 1500 IU/mL in 5% dextrose injection, a loss of 15% to 20% occurred almost instantaneously in PVC containers; additional losses to the infusion sets were minimal. However, for urokinase 5000 IU/mL in 5% dextrose injection, no losses were observed in the PVC systems. No drug loss to glass bottles was seen for urokinase 1500 or 5000 IU/mL in 5% dextrose injection. Urokinase potency remained constant in polypropylene and glass syringes for 24 hours. To minimize urokinase sorption to PVC containers, higher concentrations of urokinase diluted in 5% dextrose injection should be used, provided that clinical safety and efficacy are not compromised. The use of 0.9% sodium chloride injection as a diluent also prevents sorption losses.

  17. Multidisciplinary therapy consisting of minimally invasive resection, irradiation, and intra-arterial infusion of 5-fluorouracil for maxillary sinus carcinomas.

    PubMed

    Nishino, Hiroshi; Takanosawa, Minako; Kawada, Kazumi; Kanazawa, Takeharu; Ichimura, Keiichi; Takahashi, Satoru; Nakazawa, Masanori

    2013-06-01

    Current goals for the treatment of maxillary sinus carcinoma include the preservation of vision, eating, communication, and appearance, as well as the achievement of a cure. Japanese patients (n = 121) with maxillary sinus carcinoma were analyzed retrospectively. All patients underwent multidisciplinary therapy including minimally invasive resection, 20 Gy irradiation, and intra-arterial infusion of 5-fluorouracil. The 5- and 10-year overall survival rates were 73% and 68%, respectively. In 97 patients with squamous cell carcinoma (SCC), the 5- and 10-year overall survival rates were 76% and 70%, respectively. All 29 patients with orbital invasion retained the orbital contents, and 21 of these patients demonstrated adequate visual acuity. There were 16 complications, including trismus (5 patients), double vision (5 patients), fistula formation (3 patients), and cataract (3 patients). A multidisciplinary therapy, consisting of minimally invasive resection, irradiation, and regional chemotherapy, can yield good patient prognosis and quality of life after treatment. Copyright © 2012 Wiley Periodicals, Inc.

  18. Anesthetic management for clipping a giant basilar artery aneurysm with moderate hypothermia, extracorporeal circulation assistance, and propofol infusion.

    PubMed

    Yamada, Makiko; Nishikawa, Koichi; Kawahara, Fuminori; Yoshikawa, Daisuke; Saito, Shigeru; Goto, Fumio

    2003-07-01

    A 65-year-old female patient underwent surgery to clip a giant basilar artery aneurysm with closed-chest extracorporeal circulation using femorofemoral bypass. Moderate hypothermia (27 degrees C-30 degrees C), retention of spontaneous circulation, and propofol infusion (3-5 mg. kg(-1). h(-1)) were used under general anesthesia. Blood outflow via femoral vein was sufficient to maintain cardiopulmonary bypass and to induce hypothermia. Hemodynamics were controlled with dopamine and noradrenaline. In this case, extracorporeal circulation under moderate hypothermia was used to assist rather than substitute for spontaneous circulation, and spontaneous circulation was maintained at all times. We think that this method had advantages over deep hypothermic circulatory arrest with regard to intraoperative risks and postoperative complications.

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

    PubMed

    McAuliffe, John C; Qadan, Motaz; D'Angelica, Michael I

    2015-12-01

    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.

  20. 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

  1. [Two Cases of Effective Hepatic Arterial Infusion Chemotherapy for Liver Metastases of Colon Cancer Resistant to Systemic Chemotherapy].

    PubMed

    Date, Yusaku; Hisaka, Toru; Takahashi, Kenjiro; Nakayama, Goichi; Akashi, Masanori; Kawahara, Ryuichi; Sakai, Hisamune; Ishikawa, Hiroto; Yasunaga, Masafumi; Uchida, Shinji; Horiuchi, Hiroyuki; Okuda, Koji; Matsunaga, Mototsugu; Miwa, Keisuke; Akagi, Yoshito

    2015-11-01

    A 69-year-old man underwent right hemicolectomy for ascending colon cancer with liver metastases. Postoperative systemic chemotherapy did not reduce the metastases, and therefore, hepatic arterial infusion chemotherapy (HAI) was administered. The metastases decreased in size after 26 rounds of therapy, and the patient underwent resection. He is recurrence-free 63 months after the primary operation. A 57-year-old man underwent Hartmann's operation for sigmoid colon cancer with liver metastases. He underwent hepatic left lobe resection after metastases reduction by systemic chemotherapy. However, multiple liver metastases were detected 2 months later. Because the disease progressed despite the administration of systemic chemotherapy, HAI was utilized instead. The metastases decreased in size remarkably, and resection was performed. The patient is surviving 52 months after the primary operation while being continuously treated with HAI, resection, and systemic chemotherapy for re-recurrence. HAI is a potential alternative treatment for patients with colorectal liver metastases resistant to systemic chemotherapy.

  2. Robotic-Assisted Placement of an Hepatic Artery Infusion Pump and Catheter for Regional Chemotherapy of the Liver.

    PubMed

    Dhir, Mashaal; Magge, Deepa; Novak, Stephanie; Bartlett, David L; Zureikat, Amer H

    2016-12-01

    Hepatic artery infusion (HAI) chemotherapy is an effective regional therapy for unresectable colorectal liver metastases (U-CRLM).1 (,) 2 One of its limitations is the need for a laparotomy, which can delay the use of systemic therapy.3 Here, we describe a purely robotic technique for placement of an HAI pump (Fig 1). A 62-year-old male presented with a symptomatic ascending colon cancer and multiple bilobar unresectable liver metastases. He underwent laparoscopic right colectomy followed by six cycles of FOLFOXIRI and bevacizumab with stable disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and also underwent robotic HAI pump placement. The patient was placed supine on a split-leg table, and four robotic and two laparoscopic assistant ports were placed as shown. Use of the robot allowed for precise dissection of the common hepatic artery (CHA) and gastroduodenal artery (GDA), as well as a portal lymphadenectomy. A standard cholecystectomy was performed and the GDA was dissected for a distance of 2-3 cm from its takeoff from the CHA. The robotic scissors were used to create a precise transverse GDA arteriotomy, and the HAI pump catheter tip was advanced to the CHA/GDA junction and secured with two silk ties. Finally, a methylene blue dye injection test was performed to ensure uniform distribution within the liver. Operative time was 147 min, estimated blood loss was 20 ml, and the postoperative course was uneventful. The first dose of HAI with floxuridine was administered on postoperative day 4 (day of discharge) and systemic chemotherapy was administered 2 weeks later. The robotic platform allows for minimally invasive HAI pump placement. Fig. 1 Port placement for robotic-assisted hepatic artery infusion pump placement using the DaVinci Si platform. Illustration depicts a 12 mm periumbilical port for the robotic camera (upper green port), three 8 mm (purple) robotic working ports (the left MCL, right MCL, and right AAL for robotic arms

  3. Hepatic perfusion abnormalities during treatment with hepatic arterial infusion chemotherapy: Value of CT arteriography using an implantable port system

    SciTech Connect

    Seki, Hiroshi; Kimura, Motomasa; Kamura, Takeshi; Miura, Tsutomu

    1996-05-01

    The purpose of this study was to evaluate CT arteriography (CTA) using an implantable port system in the detection of perfusion abnormalities occurring during hepatic arterial infusion chemotherapy (HAIC). In 51 patients with unresectable primary and metastatic liver tumors, who had implanted port systems for HAIC, CTA examinations through the infusion pump were performed. When perfusion abnormalities were found, selective angiography and/or digital subtraction angiography using the implantable port system were performed to determine the etiology. Forty-nine perfusion abnormalities were detected in 32 patients. Intrahepatic hypoperfusion was found in 24 cases. Of 11 patients in whom correction of the hypoperfusion was attempted, it was successful in 10. Of 13 patients in whom correction was not attempted, 6 patients showed progressive disease in nonperfused areas. Intrahepatic hyperperfusion was found in 14 cases, which showed no subsequent complication. Extrahepatic perfusion was found in 11 cases. We consider CTA to be useful in detecting perfusion abnormalities that may compromise HAIC. 22 refs., 3 figs., 3 tabs.

  4. Detection of coronary artery disease using MR imaging with dipyridamole infusion

    SciTech Connect

    Pennell, D.J.; Underwood, S.R.; Longmore, D.B. )

    1990-03-01

    Exercise testing in the magnetic resonance (MR) scanner is difficult because of space restriction and movement artefact, which limit its use in the investigation of patients with suspected coronary artery disease. Pharmacological stress, however, can be used as a substitute for exercise. Therefore, a patient with angina underwent MR ventricular wall motion studies before and after intravenous dipyridamole. Reversible abnormal regional contraction of the myocardium was demonstrated and correlated with a reversible perfusion defect on subsequent thallium myocardial perfusion imaging and a blocked artery at coronary angiography. A clinically useful investigative procedure may be developed.

  5. Intra-arterial infusion of Solcoseryl: a clinical trial of a method of treatment for pre-gangrene of the lower limb.

    PubMed

    Charlesworth, D; Harris, P L; Palmer, M K

    1975-05-01

    A randomized double blind trial of the drug Solcoseryl given by intra-arterial infusion was carried out on 57 patients with pre-gangrene of the lower limb. A sequential analysis was carried out and the trial stopped when the results showed a statistically significant result in favour of the active drug.

  6. Early increase in arterial lactate concentration under epinephrine infusion is associated with a better prognosis during shock.

    PubMed

    Wutrich, Yann; Barraud, Damien; Conrad, Marie; Cravoisy-Popovic, Aurélie; Nace, Lionel; Bollaert, Pierre-Edouard; Levy, Bruno; Gibot, Sébastien

    2010-07-01

    To determine whether an epinephrine-induced early increase in arterial lactate concentration can prognosticate the outcome during shock state, we conducted a retrospective study in a 16-bed medical intensive care unit of a teaching hospital in France. One hundred consecutive patients admitted because of a shock state irrespective of etiology and treated with epinephrine were included. Patients were not enrolled if they received epinephrine administration before intensive care unit admission. Sequential arterial lactate measurements were performed at the time of epinephrine infusion (H0) and 4 h later (H4) in which Deltalactate was defined as (100 x [arterial lactate(H4)-arterial lactate(H0)]/arterial lactate(H0)) and expressed as a percentage. Etiology of shock was septic (82%), cardiogenic (10%), or hemorrhagic (8%). Twenty-eight-day mortality rate was 72%. At admission, arterial lactate concentration was elevated (4.96 +/- 3.8 mmol/L) and was further increased upon epinephrine administration, reaching a peak at H4 (8.22 +/- 3.66). When patients were stratified according to their outcome, nonsurvivors displayed the same pattern as survivors, although with a significant upward shift in values (ANOVA, P = 0.0003). The Sequential Organ Failure Assessment score and Deltalactate were the only variables associated with the 28-day risk of death, with an odds ratio of 1.32 (95% confidence interval [CI], 1.06-1.65; P = 0.01) and 0.99 (95% CI, 0.99-0.99; P = 0.03), respectively, in multivariate analysis. At a value of 100%, Deltalactate predicted death, with a 71% sensitivity (95% CI, 51%-87%) and a 67% specificity (95% CI, 43%-85%). Kaplan-Meier survival analysis confirmed this finding, with a 52.4% death rate among patients with Deltalactate greater than 100 comparatively to 84.7% when Deltalactate was less than 100 (log-rank test, P = 0.0002). An adapted response (lactate production) to a pharmacological trigger (epinephrine) is associated with better prognosis during

  7. 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.

  8. 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.

  9. Intra-arterial Infusion of Autologous Bone Marrow Mononuclear Stem Cells in Subacute Ischemic Stroke Patients.

    PubMed

    Ghali, Azza Abass; Yousef, Mohamed Khalil; Ragab, Osama AbdAllah; ElZamarany, Enas Arafa

    2016-01-01

    Based on many preclinical and small clinical trials, stem cells can help stroke patient with the possibility of replacing the cells and supporting the remaining cells. The aim of this study was to evaluate the safety and feasibility of bone marrow mononuclear (BMMN) stem cell transplantation in subacute ischemic stroke patients. Thirty-nine (n = 39) patients with subacute ischemic cerebral infarct due to large artery occlusion in the middle cerebral artery (MCA) territory were recruited. They were distributed into two groups: first group (n = 21) served as an experimental group, which received intra-arterial (IA) mononuclear stem cells (bone marrow-derived mononuclear cell), while the other group (n = 18) served as a control group. All the patients were evaluated clinically by National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel Index, modified and standardized Arabic version of the Comprehensive Aphasia Test, and radiological for 12 months. The stem cell-treated group showed better improvement, but it was not significant when compared with the non-treated group. The volume of infarction changes at the end of the study was non-significant between both the groups. There was no, or minimal, adverse reactions in stem cell-treated group. The study results suggest that autologous BMMN stem cell IA transplantation in subacute MCA ischemic stroke patients is safe with very minimal hazards, but no significant improvement of motor, language disturbance, or infarction volume was detected in stem cell-treated group compared with the non-treated group.

  10. Long-term effects of intermittent Iloprost infusion on pulmonary arterial pressure in connective tissue disease.

    PubMed

    Caravita, Sergio; Wu, Sheng Chin; Secchi, Maria Beatrice; Dadone, Viola; Bencini, Chiara; Pierini, Simona

    2011-10-01

    Intravenous periodic Iloprost is proven effective in the treatment of Raynaud phenomenon (RP) related to connective tissue disorder (CTD). It's well known that synthetic prostaglandins are effective drugs for the treatment of pulmonary arterial hypertension (PAH), and that PAH is frequently associated with CTD. The aim of the study is to evaluate in the chronic effect of cyclic intravenous Iloprost on pulmonary arterial pressure. We studied 17 consecutive patients with CTD (14 systemic sclerosis, 3 mixed CTD) and RP, at the entry and after at least 6months of treatment of RP with cyclic Iloprost. On both occasions, in all patients we performed transthoracic Doppler echocardiography and we determined NT-proBNP plasma levels, NYHA functional class, 6 Minute-Walk Distance (6MWD). At follow-up (8.2±1.9months; range 6-12) mean values of pulmonary arterial systolic pressure (PASP) significantly decreased (from 32.2±9.2 to 29.2±7.6mmHg, p<0.04) and mean values of 6MWD significantly increased (from 407.5±101.5 to 448.3±89.9m, p<0.01). Moreover, we observed a significant direct correlation between PASP and NT-proBNP values and a significant inverse correlation both between NT-proBNP and 6MWD values and between PASP and 6MWD values. Our results suggest that cyclic intravenous Iloprost may protect against the development or worsening of PAH in patients with CTD and RP. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  11. 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. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  12. 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

  13. Adjuvant Hepatic Arterial Infusion Chemotherapy After Resection for Pancreatic Cancer Using Coaxial Catheter-Port System Compared with Conventional System.

    PubMed

    Hashimoto, Aya; Tanaka, Toshihiro; Sho, Masayuki; Nishiofuku, Hideyuki; Masada, Tetsuya; Sato, Takeshi; Marugami, Nagaaki; Anai, Hiroshi; Sakaguchi, Hiroshi; Kanno, Masatoshi; Tamamoto, Tetsuro; Hasegawa, Masatoshi; Nakajima, Yoshiyuki; Kichikawa, Kimihiko

    2016-06-01

    Previous reports have shown the effectiveness of adjuvant hepatic arterial infusion chemotherapy (HAIC) in pancreatic cancer. However, percutaneous catheter placement is technically difficult after pancreatic surgery. The purpose of this study was to evaluate the feasibility and outcome of HAIC using a coaxial technique compared with conventional technique for postoperative pancreatic cancer. 93 consecutive patients who received percutaneous catheter-port system placement after pancreatectomy were enrolled. In 58 patients from March 2006 to August 2010 (Group A), a conventional technique with a 5-Fr indwelling catheter was used and in 35 patients from September 2010 to September 2012 (Group B), a coaxial technique with a 2.7-Fr coaxial catheter was used. The overall technical success rates were 97.1 % in Group B and 86.2 % in Group A. In cases with arterial tortuousness and stenosis, the success rate was significantly higher in Group B (91.7 vs. 53.8 %; P = 0.046). Fluoroscopic and total procedure times were significantly shorter in Group B: 14.7 versus 26.7 min (P = 0.001) and 64.8 versus 80.7 min (P = 0.0051), respectively. No differences were seen in the complication rate. The 1 year liver metastasis rates were 9.9 % using the conventional system and 9.1 % using the coaxial system (P = 0.678). The overall median survival time was 44 months. There was no difference in the survival period between two systems (P = 0.312). The coaxial technique is useful for catheter placement after pancreatectomy, achieving a high success rate and reducing fluoroscopic and procedure times, while maintaining the safety and efficacy for adjuvant HAIC in pancreatic cancer.

  14. Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series.

    PubMed

    Nemoto, Tomoyuki; Matsuda, Hidetaka; Nosaka, Takuto; Saito, Yasushi; Ozaki, Yoshihiko; Hayama, Ryoko; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Ohtani, Masahiro; Hiramatsu, Katsushi; Suto, Hiroyuki; Nakamoto, Yasunari

    2014-11-01

    Sorafenib and hepatic arterial infusion chemotherapy (HAIC) are both indicated for unresectable hepatocellular carcinoma (HCC). In this study, we compared the efficacy and safety of HAIC to that of sorafenib in elderly patients with HCC. Eligible patients included those aged ≥70 years, with histologically or clinically confirmed advanced HCC. A total of 12 patients received sorafenib (800 mg per day) and 8 patients received HAIC with 5-fluorouracil (300 mg/m(2) on days 1-5 and 8-12) with or without cisplatin (20 mg/m(2) on days 1 and 8), with interferon-α (3 times per week for 4 weeks). The response rate was significantly higher in patients treated with HAIC (37.5%) compared to that in patients treated with sorafenib (no response). The median overall survival (18.6 and 11.7 months) and progression-free survival (4.0 and 5.0 months) were similar between the sorafenib and HAIC groups, respectively. In the sorafenib group, 58.3% of the patients discontinued treatment compared to none in the HAIC group. The most frequent adverse event leading to discontinuation of sorafenib was anorexia. Similar to sorafenib, HAIC appears to be a feasible treatment and may also have the advantage of an adequate safety profile for elderly patients with advanced HCC. Further study of HAIC in a larger population of elderly patients is required to assess its potential as an alternative to sorafenib for HCC.

  15. Comparison of hepatic arterial infusion chemotherapy and sorafenib in elderly patients with advanced hepatocellular carcinoma: A case series

    PubMed Central

    NEMOTO, TOMOYUKI; MATSUDA, HIDETAKA; NOSAKA, TAKUTO; SAITO, YASUSHI; OZAKI, YOSHIHIKO; HAYAMA, RYOKO; NAITO, TATSUSHI; TAKAHASHI, KAZUTO; OFUJI, KAZUYA; OHTANI, MASAHIRO; HIRAMATSU, KATSUSHI; SUTO, HIROYUKI; NAKAMOTO, YASUNARI

    2014-01-01

    Sorafenib and hepatic arterial infusion chemotherapy (HAIC) are both indicated for unresectable hepatocellular carcinoma (HCC). In this study, we compared the efficacy and safety of HAIC to that of sorafenib in elderly patients with HCC. Eligible patients included those aged ≥70 years, with histologically or clinically confirmed advanced HCC. A total of 12 patients received sorafenib (800 mg per day) and 8 patients received HAIC with 5-fluorouracil (300 mg/m2 on days 1–5 and 8–12) with or without cisplatin (20 mg/m2 on days 1 and 8), with interferon-α (3 times per week for 4 weeks). The response rate was significantly higher in patients treated with HAIC (37.5%) compared to that in patients treated with sorafenib (no response). The median overall survival (18.6 and 11.7 months) and progression-free survival (4.0 and 5.0 months) were similar between the sorafenib and HAIC groups, respectively. In the sorafenib group, 58.3% of the patients discontinued treatment compared to none in the HAIC group. The most frequent adverse event leading to discontinuation of sorafenib was anorexia. Similar to sorafenib, HAIC appears to be a feasible treatment and may also have the advantage of an adequate safety profile for elderly patients with advanced HCC. Further study of HAIC in a larger population of elderly patients is required to assess its potential as an alternative to sorafenib for HCC. PMID:25279193

  16. Hepatic arterial infusion plus systemic chemotherapy as third-line or later treatment in colorectal liver metastases.

    PubMed

    Qiang, W-G; Shi, L-R; Li, X-D; Wu, Q-Q; Zhao, J-M; Chen, L-J; Yang, Y; Wu, J; Ji, M; Wu, C-P

    2015-11-01

    The present study aimed to evaluate benefit of hepatic arterial infusion chemotherapy (HAI) combined with systemic chemotherapy (SCT) for patients with colorectal liver metastases (CLMs) in a palliative setting. This was a retrospective single-center study including 43 consecutive patients with CLM after failure of standard SCT. Among them, 20 (47 %) patients underwent HAI combined with SCT (Group A) and 23 historical control patients who had received SCT with or without targeted agent treatment (Group B). The two groups had similar characteristics. Compared with SCT alone, HAI combined with SCT prolonged survival (median 19.8 vs. 9.0 months; P = 0.045). Median hepatic progression-free survival was significantly longer for HAI combined with SCT vs. SCT alone (median 8.1 vs. 4.7 months; P = 0.027), as were response rates (25 and 0 %; P = 0.038) and progression-free survival (median 5.7 vs. 3.0 months; P = 0.02). Three patients (15 %) achieved conversion to potentially curative surgery. Grade 3/4 toxicities for Group A and Group B were neutropenia (5 and 8.7 %, respectively), anemia (5 and 0 %, respectively), and hyperbilirubinemia (0 and 4.3 %, respectively). Other complications were mostly grade 1 or 2. HAI combined with SCT treatment can improve overall survival compared with SCT alone in highly advanced CLM refractory to intravenous chemotherapy.

  17. The use of micro-dose aprotinin with continuous infusion in coronary artery bypass surgery.

    PubMed

    Holmes, J H; Jones, M F; Anderson, R P; Knopes, K D; Guyton, S W; Hall, R A

    1999-10-01

    To evaluate the efficacy of aprotinin at a dose far less than standard. Retrospective, case-control study. community-based, teaching hospital one hundred one patients undergoing primary, non-emergent, coronary artery bypass during two, six-month periods were studied. during the first period aprotinin was not administered, and these patients served as controls (n = 52). During the second period all patients received aprotinin via a micro-dose regimen (n = 49). postoperative bleeding and blood product usage served as determinants of efficacy. A significant difference existed in postoperative bleeding with the mean thoracic drain outputs being reduced in the aprotinin group both at 6 hours (p = 0.0003) and in total (p = 0.0004). This was further supported by significantly higher hematocrits (p = 0.03) on the first postoperative day in patients receiving aprotinin. Likewise, there was a significant reduction in total blood product exposures (p = 0.04) and platelet usage (p = 0.02) in the aprotinin group with a tendency towards decreased red cell usage. Further, when all patients with a hematocrit < or =30% prior to bypass were excluded, the significant reduction in total blood product exposures persisted (p = 0.04), and there was a significant reduction in red cell usage (p = 0.04) with a trend towards decreased platelet usage (p = 0.06) in the aprotinin group. Micro-dose aprotinin significantly reduces postoperative bleeding and blood product usage in primary, non-emergent, CABG patients.

  18. In vivo distribution of recombinant interleukin-2-activated autologous lymphocytes administered by intra-arterial infusion in patients with renal cell carcinoma

    SciTech Connect

    Morita, T.; Yonese, Y.; Minato, N.

    1987-03-01

    Recombinant interleukin-2 (RIL 2)-activated autologous peripheral blood lymphocytes (PBL) were infused directly into the renal arteries of 3 patients with renal cell carcinoma, and the in vivo distribution of the infused cells was investigated. In vitro studies to define the optimal culture conditions indicated that maximal lymphokine-activated killer activity was observed at around 10-20 days in culture, as judged by the cytotoxicity against fresh allogenic tumor cells. Maximal expression of the interleukin-2 receptor was also obtained at around 10 days. PBL collected by leukopheresis from each patient were thus cultured for 10 days with RIL 2, labeled with /sup 111/In-oxine, and then infused directly into the renal artery of the affected kidney via a catheter. Radioactivity in the infused side of the kidneys increased immediately after the infusion but then gradually decreased. Radioactivity in the lungs also rapidly increased within the first hour but then cleared gradually, whereas that in the liver and spleen tended to increase steadily. Nevertheless, at 48 hours, the infused side of the kidneys retained levels of radioactivity comparable to those seen in the liver and spleen, while the levels seen in the lungs were already close to background levels. The radioactivity in the areas corresponding to tumors remained consistently higher than that in the normal parts of the affected kidneys. The direct comparison of the radioactivity distribution pattern with the macroscopic appearance of surgically resected kidneys indicated that the accumulation of radioactivity was indeed selectively associated with the tumor tissues in the kidneys, except for a case in which the tumor was quite necrotic and hypovascular.

  19. [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.

  20. A randomized study of cisplatin and 5-FU hepatic arterial infusion chemotherapy with or without adriamycin for advanced hepatocellular carcinoma.

    PubMed

    Song, Myeong Jun; Bae, Si Hyun; Chun, Ho Jong; Choi, Jong Young; Yoon, Seung Kew; Park, Jun Young; Han, Kwang Hyub; Kim, Young Seok; Yim, Hyung Joon; Um, Soon Ho; Chung, Woo Jin; Hwang, Jae Seok; Cho, Sung-Bum; Eun, Jong Ryul

    2015-04-01

    This multicenter, randomized, open-labeled, clinical trial evaluated the efficacy and safety of cisplatin/5-fluorouracil (5-FU) hepatic arterial infusion chemotherapy (CF-HAIC) versus adriamycin adding to CF-HAIC (ACF-HAIC) in advanced HCC patients. Fifty-six patients with advanced HCC were randomized to two treatment groups: (1) CF-HAIC group [n = 29, 5-FU, 500 mg/m(2) on days 1-3, and cisplatin, 60 mg/m(2) on day 2] and (2) ACF-HAIC group [n = 27, adriamycin, 50 mg/m(2) on day 1, 5-FU, 500 mg/m(2) on days 1-3, and cisplatin, 60 mg/m(2) on day 2] every 4 weeks via an implantable port system. Primary efficacy endpoint was overall survival (OS). Treatment response and time to progression were secondary endpoints. Treatment response rates did not differ significantly between the two treatment groups. Time to progression (5.4 vs. 5.8 months, P = 0.863) and OS (11.1 vs. 8.8 months, P = 0.448) were not significantly different. When the factors affecting patient OS were analyzed, disease control rate [P < 0.001, HR 6.437 (95% CI 2.580-16.064)] was independently associated with OS. Age (≥60 years) and serum AFP level (≥200 ng/dL) also were significant factors for OS [P = 0.007, HR 4.945 (95% CI 1.543-15.850), P = 0.048, HR 2.677 (95% CI 1.010-7.095), respectively]. Grade 4 treatment-related toxicity and mortality was not observed in both groups. Although both HAIC regimens are safe and effective in patients with advanced HCC, HAIC adding adriamycin did not show delayed tumor progression and survival benefit compared to CF-HAIC in advanced HCC.

  1. Increasing the effective concentration of melphalan in experimental rat liver tumours: comparison of isolated liver perfusion and hepatic artery infusion.

    PubMed Central

    Marinelli, A.; van Dierendonck, J. H.; van Brakel, G. M.; Irth, H.; Kuppen, P. J.; Tjaden, U. R.; van de Velde, C. J.

    1991-01-01

    Regional chemotherapy allows further exploitation of the steep dose response curve of most chemotherapeutic agents, while systemic toxicity remains tolerable. We investigated the difference in maximally tolerated dose, pharmacokinetics and antitumour effect comparing administration of melphalan as a bolus in isolated liver perfusion (ILP) or via hepatic artery infusion (HAI). For these in vivo studies an experimental model for liver metastases in male WAG/Ola rats is obtained by subcapsular inoculation of CC531 rat colon carcinoma cells. In this system, ILP allowed administration of a two times higher dose than HAI (12 mg kg-1 vs 6 mg kg-1). In both treatment modalities systemic toxicity (leukopenia) was dose limiting. No hepatic toxicity was observed. Bolus administration of the maximally tolerated doses of melphalan in HAI (6 mg kg-1) and ILP (12 mg kg-1) resulted in four times higher concentrations in both liver and tumour tissue of the ILP treated rats. However, the ratio of mean drug concentration in liver vs tumour tissue appeared to be 1.5 times that found for HAI. In the range of the in tumour tissue measured melphalan concentrations the CC531 cells showed a steep dose response relationship in vitro. Whereas HAI resulted in significant tumour growth delay, complete remissions were observed in 90% of the rats treated with ILP. This study shows that with 12 mg kg-1 melphalan in ILP highly effective drug concentrations are achieved in CC531 tumour tissue; although the melphalan concentration in liver tissue shows an even higher increase than in tumour tissue, hepatic toxicity is negligible in this dose range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1764369

  2. Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis

    PubMed Central

    Zhang, Hangyu; Guo, Jianhai; Gao, Song; Zhang, Pengjun; Chen, Hui; Wang, Xiaodong; Li, Xiaoting; Zhu, Xu

    2017-01-01

    Objective To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis (CRCLM) patients treated by transarterial chemoembolization (TACE) and sustained hepatic arterial infusion chemotherapy (HAIC). Methods Between 2006 and 2015, 162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study, including 110 males and 52 females, with a median age of 60 (range, 26–83) years. Prognostic factors were assessed with Log-rank test, Cox univariate and multivariate analyses. Results The median survival time (MST) and median progression-free survival (PFS) of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively. Normal serum carbohydrate antigen 19-9 (CA19-9, <37 U/mL) (P<0.001) and carbohydrate antigen 72-4 (CA72-4, <6.7 U/mL) (P=0.026), combination with other local treatment (liver radiotherapy or liver radiofrequency ablation) (P=0.034) and response to TACE/HAIC (P<0.001) were significant factors related to survival after TACE/HAIC in univariate analysis. A multivariate analysis revealed that normal serum CA19-9 (P<0.001), response to TACE/HAIC (P<0.001) and combination with other local treatment (P=0.001) were independent factors among them. Conclusions Our findings indicate that serum CA19-9 <37 U/mL and response to TACE/HAIC are significant prognostic indicators for this combined treatment, and treated with other local treatment could reach a considerable survival benefit for CRCLM. This could be useful for making decisions regarding the treatment of CRCLM. PMID:28373752

  3. Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone.

    PubMed

    Konstantinidis, Ioannis T; Groot Koerkamp, Bas; Do, Richard K G; Gönen, Mithat; Fong, Yuman; Allen, Peter J; D'Angelica, Michael I; Kingham, T Peter; DeMatteo, Ronald P; Klimstra, David S; Kemeny, Nancy E; Jarnagin, William R

    2016-03-01

    Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone. Consecutive patients with ICC were retrospectively reviewed. Clinicopathologic data were reviewed. Survival rates were compared by Kaplan-Meier analysis and log-rank testing. Between January 2000 and August 2012, 525 patients with ICC were evaluated at Memorial Sloan Kettering Cancer Center, and 236 patients with unresectable tumors (locally advanced or metastatic) were analyzed. Disease was confined to the liver in 104 patients, who underwent treatment with combined HAI and SYS (n = 78 or 75%) or SYS alone (n = 26 or 25%). The response rate in the combined group was better than the rate in the group receiving SYS alone, although this did not reach statistical significance (59% vs 39%, P = .11). Overall survival for the combined group was longer than overall survival for the patients who received SYS alone (30.8 vs 18.4 months, P < .001), and this difference was maintained when patients with portal lymph node disease were included in the survival analysis (29.6 months with HAI and SYS [n = 93] vs 15.9 months with SYS [n = 74], P < .001). Eight patients who initially presented with unresectable tumors responded enough to undergo complete resection and had a median overall survival of 37 months (range, 10.4-92.3 months). In patients with unresectable ICC confined to the liver or with limited regional nodal disease, a combination of SYS and HAI chemotherapy is associated with greater survival than SYS alone. Cancer 2016;122:758-765. © 2015 American Cancer Society. © 2015 American Cancer Society.

  4. 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.

  5. 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.

  6. Randomized comparison of closed-loop feedback computer-controlled with manual-controlled infusion of phenylephrine for maintaining arterial pressure during spinal anaesthesia for caesarean delivery.

    PubMed

    Ngan Kee, W D; Khaw, K S; Ng, F F; Tam, Y H

    2013-01-01

    Closed-loop feedback computer-controlled infusion has not been described for administering phenylephrine to maintain arterial pressure (AP) during spinal anaesthesia for caesarean delivery. We aimed to compare AP control using this automated system with a previously described manual infusion system. We randomly allocated 222 healthy subjects having spinal anaesthesia for scheduled caesarean delivery to have systolic AP maintained near baseline with phenylephrine (100 µg ml(-1)) by computer-controlled infusion utilizing a proportional algorithm or manual-controlled infusion utilizing an on-off algorithm. AP control was assessed by comparing the proportion of systolic AP measurements within ±20% of baseline and by performance error (PE) calculations. A total of 212 subjects finished the study. In the computer-control group, 97% of systolic AP recordings fell within ±20% of baseline compared with 95% in the manual-control group (P=0.0004). For computer-control compared with manual-control, wobble was smaller [median 3.5 (inter-quartile range 2.5-4.8)% vs 4.2 (3.3-5.9)%, P=0.003], but there was no difference in the median PE [2.9 (0.3-4.7)% vs 1.9 (0-4.2)%], median absolute PE [4.7 (3.5-5.6)% vs 4.7 (3.8-6.7)%], or divergence [-0.01 (-0.03-0)% vs -0.06 (-0.26-0.08)%]. Fewer interventions per subject for controlling AP were required in the computer-control group [2 (2-2) vs 10 (8-13), P<0.001]. There were no differences in measured clinical outcomes. Within the constraints of the studied algorithms, closed-loop feedback computer-controlled phenylephrine infusion provided better AP control with fewer interventions required compared with manual-controlled infusion.

  7. Differential Clearance of Rat and Human Bone Marrow-Derived Mesenchymal Stem Cells From the Brain After Intra-arterial Infusion in Rats.

    PubMed

    Khabbal, Joonas; Kerkelä, Erja; Mitkari, Bhimashankar; Raki, Mari; Nystedt, Johanna; Mikkonen, Ville; Bergström, Kim; Laitinen, Saara; Korhonen, Matti; Jolkkonen, Jukka

    2015-01-01

    Intra-arterial (IA) delivery of bone marrow-derived mesenchymal stem cells (BM-MSCs) has shown potential as a minimally invasive therapeutic approach for stroke. The aim of the present study was to determine the whole-body biodistribution and clearance of technetium-99m ((99m)Tc)-labeled rat and human BM-MSCs after IA delivery in a rat model of transient middle cerebral artery occlusion (MCAO) using single-photon emission computed tomography (SPECT). Our hypothesis was that xenotransplantation has a major impact on the behavior of cells. Male RccHan:Wistar rats were subjected to sham operation or MCAO. Twenty-four hours after surgery, BM-MSCs (2 × 10(6) cells/animal) labeled with (99m)Tc were infused into the external carotid artery. Whole-body SPECT images were acquired 20 min, 3 h, and 6 h postinjection, after which rats were sacrificed, and organs were collected and weighed for measurement of radioactivity. The results showed that the majority of the cells were located in the brain and especially in the ipsilateral hemisphere immediately after cell infusion both in sham-operated and MCAO rats. This was followed by fast disappearance, particularly in the case of human cells. At the same time, the radioactivity signal increased in the spleen, kidney, and liver, the organs responsible for destroying cells. Further studies are needed to demonstrate whether differential cell behavior has any functional impact.

  8. 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.

  9. Efficacy and safety of intra-arterial steroid infusions in patients with steroid-resistant gastrointestinal acute graft-versus-host disease.

    PubMed

    Nishimoto, Mitsutaka; Koh, Hideo; Hirose, Asao; Nakamae, Mika; Nakane, Takahiko; Hayashi, Yoshiki; Okamura, Hiroshi; Yoshimura, Takuro; Koh, Shiro; Nanno, Satoru; Nakashima, Yasuhiro; Takeshita, Toru; Yamamoto, Akira; Sakai, Yukimasa; Nishida, Norifumi; Matsuoka, Toshiyuki; Miki, Yukio; Hino, Masayuki; Nakamae, Hirohisa

    2015-12-01

    There is no established second-line treatment for steroid-resistant acute graft-versus-host disease (GVHD). We prospectively assessed the safety and efficacy of intra-arterial steroid infusions (IASIs) for steroid-resistant acute gastrointestinal (GI) GVHD and compared the outcomes with those of historical controls at our institution. Nineteen consecutive, allogeneic hematopoietic stem cell transplantation subjects aged 31-67 years (median 52) were enrolled between October, 2008, and November, 2012. Acute GVHD was confirmed by biopsy in all cases. The enrolled patients were treated with infusions of methylprednisolone into the mesenteric arteries and/or gastroduodenal and left gastric arteries. Fourteen consecutive patients who developed steroid-resistant acute GI GVHD between 2001 and 2008 were used as controls. For the primary endpoint at day 28, the overall and complete responses in the IASI group trended higher (79% vs. 42%, p = 0.066) and were significantly higher (63% vs. 21%, p = 0.033) than those in the control group. Although not statistically significant, owing to the small population, the crude day-180-nonrelapse mortality rate was about 20% lower and the day-180-overall-survival rate tended to be higher than the control (11% vs. 29%, p = 0.222; 79% vs. 50%, p = 0.109, respectively). There were no serious IASI-related complications. Our results suggest that IASI can safely provide excellent efficacy for refractory acute GI GVHD without increasing infection-related complications and may improve prognosis.

  10. Superparamagnetic iron oxide-enhanced liver MRI with SHU 555 A (RESOVIST): New protocol infusion to improve arterial phase evaluation--a prospective study.

    PubMed

    Grazioli, Luigi; Bondioni, Maria Pia; Romanini, Laura; Frittoli, Barbara; Gambarini, Sebastiana; Donato, Francesco; Santoro, Lucia; Colagrande, Stefano

    2009-03-01

    To compare the arterial enhancement of hypervascular hepatic lesions by T1-weighted 3D-GRE (gradient-recalled echo) fat-sat sequence after slow (0.5 mL/sec) and fast (2 mL/sec) RESOVIST infusion. We prospectively enrolled 71 patients with hypervascular hepatic lesions to undergo dynamic magnetic resonance imaging (MRI) examination with RESOVIST. A total of 92 benign and malignant lesions, 44 of which histologically confirmed, were examined. Three blinded and independent readers visually assessed the arterial enhancement using a score from 0 (none) to 3 (maximum), the latter score comparable to that achievable by MultiHance administration. Out of the 92 hypervascular lesions, 41, 31, and 20 nodules were examined using the slow, fast, and both protocols, respectively. Relevant enhancement (scores 2-3) was found in 42% vs. 14.5% of cases for slow and fast protocols, respectively. Intraindividual comparison evaluation confirmed the better results obtained by slow than fast protocol (25% vs. 10%), with statistically relevant difference in distribution of scores (P=0.0004). The slow protocol showed values between 0 and 3 with an arithmetic mean of 1.1; the fast one, on the other hand, showed values between 0 and 2 with an arithmetic mean of 0.66. Slow infusion improves arterial enhancement after RESOVIST administration. Copyright (c) 2009 Wiley-Liss, Inc.

  11. Comparison of bolus and continuous infusion of esmolol on hemodynamic response to laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft.

    PubMed

    Efe, Esra Mercanooglu; Bilgin, Basak Atabey; Alanoglu, Zekeriyya; Akbaba, Murat; Denker, Cigdem

    2014-01-01

    The aim of this randomized, prospective and double blinded study is to investigate effects of different esmolol use on hemodynamic response of laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft surgery. After approval of local ethics committee and patients' written informed consent, 45 patients were randomized into three groups equally. In Infusion Group; from 10 min before intubation up to 5th minute after sternotomy, 0.5mg/kg/min esmolol infusion, in Bolus Group; 2 min before intubation and sternotomy 1.5mg/kg esmolol IV bolus and in Control Group; %0.9 NaCl was administered. All demographic parameters were recorded. Heart rate and blood pressure were recorded before infusion up to anesthesia induction in every minute, during endotracheal intubation, every minute for 10 minutes after endotracheal intubation and before, during and after sternotomy at first and fifth minutes. While area under curve (AUC) (SAP×time) was being found more in Group B and C than Group I, AUC (SAP×Tint and Tst) and AUC (SAP×T2) was found more in Group B and C than Group I (p<0.05). Moreover AUC (HR×Tst) was found less in Group B than Group C but no significant difference was found between Group B and Group I. This study highlights that esmolol infusion is more effective than esmolol bolus administration on controlling systolic arterial pressure during endotracheal intubation and sternotomy in CABG surgery. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  12. [Comparison of bolus and continuous infusion of esmolol on hemodynamic response to laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft].

    PubMed

    Efe, Esra Mercanooglu; Bilgin, Basak Atabey; Alanoglu, Zekeriyya; Akbaba, Murat; Denker, Cigdem

    2014-01-01

    The aim of this randomized, prospective and double blinded study is to investigate effects of different esmolol use on hemodynamic response of laryngoscopy, endotracheal intubation and sternotomy in coronary artery bypass graft surgery. After approval of local ethics committee and patients' written informed consent, 45 patients were randomized into three groups equally. In Infusion Group; from 10 min before intubation up to 5th minute after sternotomy, 0.5 mg/kg/min esmolol infusion, in Bolus Group; 2 min before intubation and sternotomy 1.5 mg/kg esmolol IV bolus and in Control Group; %0.9 NaCl was administered. All demographic parameters were recorded. Heart rate and blood pressure were recorded before infusion up to anesthesia induction in every minute, during endotracheal intubation, every minute for 10 minutes after endotracheal intubation and before, during and after sternotomy at first and fifth minutes. While area under curve (AUC) (SAP × time) was being found more in Group B and C than Group I, AUC (SAP × Tint and Tst) and AUC (SAP × T2) was found more in Group B and C than Group I (p < 0.05). Moreover AUC (HR × Tst) was found less in Group B than Group C but no significant difference was found between Group B and Group I. This study highlights that esmolol infusion is more effective than esmolol bolus administration on controlling systolic arterial pressure during endotracheal intubation and sternotomy in CABG surgery. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  13. [Evaluation of intra-arterial infusion chemotherapy for liver metastasis from gastric cancer FEM--combination therapy of 5 FU, Epirubicin and MMC].

    PubMed

    Takada, Joji; Katsuki, Yoshio; Hamada, Hiromi; Tsuji, Yasushige

    2002-11-01

    We evaluated the effectiveness of FEM (5-FU, Epirubicin, MMC) therapy. One hundred ten cases of liver metastasis from gastric cancer were collected from January, 1977 until June, 2001 (synchronous: 74 cases, asynchronous: 36 cases). Twenty-nine cases were H1, 20 cases were H2 and 61 cases were H3. The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 9); Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intra-arterial infusion (4 cases). Group B: Resection of the primary lesion (n = 67); Group B1: Resection of the primary lesion only (46 cases), Group B2: Intra-arterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (3 cases) and B2a (8 cases). Non-FEM therapy was applied to A2b (1 case) and B2b (13 cases). Group C consisted of 34 cases in which resection of the primary lesion was not undertaken. Survival rates were then compared. One-year survival rates and 50% survival period for each group were as follows: Group A: 33%, 5.9 months; Group B: 22%, 4.8 months; and Group C: 6%, 3.9 months, respectively. Five patients from Groups A2a and B2a survived for one year or longer. 1. The prognosis with liver metastasis from gastric cancer, even with a number of therapies, is not promising. 2. Resection of the primary lesion along with hepatic intra-arterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended survival.

  14. A simple catheter-vessel model for MR assessment of drug distribution in arteries and optimization of catheter design for intraarterial infusion therapy.

    PubMed

    Yoshikawa, Takeshi; Uchida, Koji; Ohno, Yoshiharu; Hirota, Shozo; Nakamura, Tomonori; Yoshizako, Takeshi; Ishida, Jun; Kitagaki, Hajime

    2007-05-01

    To investigate the efficacy of a new catheter-vessel model for MRI to evaluate drug distribution and to optimize catheter design for intraarterial infusion therapy The model consisted of a hepatic artery simulant tube through which blood simulant water flowed continuously and a water cistern. Catheters were inserted into the tube and a gadolinium contrast medium was injected at rates suitable for angiographic or computed tomographic evaluation and commensurate with the clinical drug infusion rate. Axial images of the tube were obtained with a 0.2-T scanner and gradient echo technique. Preliminary studies and catheter tests were conducted. The points at which drug and water were completely mixed were defined as the site with uniform enhancement nearest the catheter tip. Flip angle and gadolinium concentrations were optimized at 90 degrees, and at 62.5 and 500 mM for the high and low infusion rates, respectively. Drug distribution near the catheter tips was clearly visualized. The drug was mixed in shorter distances via the slit side-hole than the end- or side-hole catheters, and the smaller diametrical than the larger at either rate. This model appeared to be effective for evaluation of drug distribution and optimization of catheter design. (c) 2007 Wiley-Liss, Inc.

  15. 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.

  16. 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

  17. 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.

  18. A case of central diabetes insipidus after ketamine infusion during an external to internal carotid artery bypass.

    PubMed

    Gaffar, Sharib; Eskander, Jonathan P; Beakley, Burton D; McClure, Brian P; Amenta, Peter; Pierre, Nakeisha

    2017-02-01

    We report the first teenage case of ketamine-induced transient central diabetes insipidus. The patient was an 18-year-old woman with moyamoya disease undergoing an external carotid to internal carotid bypass and given a low-dose ketamine infusion. After approximately 2 hours in the supine position, with 0.5 Minimum Alveolar Concentration (MAC) of sevoflurane, a propofol infusion at 50 μg/kg/min, a remifentanil infusion at 0.5 μg/kg/min, and a ketamine infusion at a dose of 10 μg/kg/min, this patient had an excessive urine output. Initially, the Foley catheter contained 50 mL of urine. She was given 1500 mL of crystalloid during the case but produced 2700 mL of urine output. Increasing urine output was noted 1 hour into the procedure around the time that the patient experienced a 2-minute Cushing-like response characterized by bradycardia and hypertension. Several I-Stat samples revealed a worsening hypernatremia. The decision was made to check the urine osmolality and treat the patient with 4 μg of desmopressin (DDAVP). Urine output began to slow down to a normal rate of 2 mg/kg/h, as the patient was transferred from the operating room to the computed tomographic (CT) scanning room for a CT and CT angiogram; both were unremarkable. The neurosurgery team waited until the next day to complete the procedure. The procedure was completed successfully and uneventfully the next day without a ketamine infusion as part of the general anesthetic plan. The Naranjo Adverse Drug Reaction score of 4 suggested a possible relationship between the patient's ketamine infusion and subsequent central diabetes insipidus. The 2 previous cases on this topic have suggested that ketamine, as an N-methyl-d-aspartate receptor antagonist, inhibits vasopressin release in the neurohypophysis. Urine output, urine osmolarity, and serum osmolarity should be monitored in patients given ketamine anesthetic; desmopressin should be present to prevent dangerous long-term sequela. Copyright © 2016

  19. Arterial acid-base status during digestion and following vascular infusion of NaHCO(3) and HCl in the South American rattlesnake, Crotalus durissus.

    PubMed

    Arvedsen, Sine K; Andersen, Johnnie B; Zaar, Morten; Andrade, Denis; Abe, Augusto S; Wang, Tobias

    2005-12-01

    Digestion is associated with gastric secretion that leads to an alkalinisation of the blood, termed the "alkaline tide". Numerous studies on different reptiles and amphibians show that while plasma bicarbonate concentration ([HCO(3)(-)](pl)) increases substantially during digestion, arterial pH (pHa) remains virtually unchanged, due to a concurrent rise in arterial PCO(2) (PaCO(2)) caused by a relative hypoventilation. This has led to the suggestion that postprandial amphibians and reptiles regulate pHa rather than PaCO(2). Here we characterize blood gases in the South American rattlesnake (Crotalus durissus) during digestion and following systemic infusions of NaHCO(3) and HCl in fasting animals to induce a metabolic alkalosis or acidosis in fasting animals. The magnitude of these acid-base disturbances were similar in magnitude to that mediated by digestion and exercise. Plasma [HCO(3)(-)] increased from 18.4+/-1.5 to 23.7+/-1.0 mmol L(-1) during digestion and was accompanied by a respiratory compensation where PaCO(2) increased from 13.0+/-0.7 to 19.1+/-1.4 mm Hg at 24 h. As a result, pHa decreased slightly, but were significantly below fasting levels 36 h into digestion. Infusion of NaHCO(3) (7 mmol kg(-1)) resulted in a 10 mmol L(-1) increase in plasma [HCO(3)(-)] within 1 h and was accompanied by a rapid elevation of pHa (from 7.58+/-0.01 to 7.78+/-0.02). PaCO(2), however, did not change following HCO(3)(-) infusion, which indicates a lack of respiratory compensation. Following infusion of HCl (4 mmol kg(-1)), plasma pHa decreased by 0.07 units and [HCO(3)(-)](pl) was reduced by 4.6 mmol L(-1) within the first 3 h. PaCO(2), however, was not affected and there was no evidence for respiratory compensation. Our data show that digesting rattlesnakes exhibit respiratory compensations to the alkaline tide, whereas artificially induced metabolic acid-base disturbances of same magnitude remain uncompensated. It seems difficult to envision that the central and

  20. High dose of green tea infusion normalized spiral artery density in rats treated with the depot-medroxyprogesterone acetate.

    PubMed

    Emilda, A S; Veri, Nora; Alchalidi, Alchalidi

    2017-01-01

    The purpose of this study was to investigate the effects of green tea (GT) on the spiral artery density and endometrial thickness in female rats treated with the depot-medroxyprogesterone acetate (DMPA). A total of 24 female rats were randomly divided into four groups (n = 6 each): The control group (no treatment), the DMPA-treated group, treated with DMPA and GT doses of 165 mg/kg of body weight/day, and treated with DMPA and GT doses of 330 mg/kg of body weight/day. Spiral artery density and endometrial thickness were subjected to histopathological analysis. Spiral artery density decreased in the DMPA-treated group, despite the insignificant difference (P > 0.05). With regard to the administration of GT at doses of 165 and 330 mg/g of body weight/day, only GT at the high dose was capable of significantly preventing a decrease in spiral artery density (P < 0.05). At this dose, the spiral arteries achieved a density comparable to that of the control group (P > 0.05). Meanwhile, the administration of DMPA and/or DMPA with GT did not cause significant changes in endometrial thickness relative to the control group (P > 0.05). DMPA induced a decrease in spiral artery density, despite the insignificant differences, and these changes could be normalized by the administration of high doses of GT. Therefore, GT could be a candidate herb to prevent the adverse effects of the contraceptive DMPA.

  1. 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.

  2. 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.

  3. [Effect of arterial infusion with methylene blue during total mesorectal excision on urination function and sexual function in male patients with rectal cancer].

    PubMed

    He, Xiaowen; Li, Guangquan; Zhang, Ruijiang; Wang, Jindao

    2016-04-01

    To explore the effect of arterial infusion with methylene blue during total mesorectal excision (TME) for better preservation of pelvic autonomic nerve on urination function and sexual function in male patients with rectal cancer. A total of 68 male rectal cancer patients from Zhejiang Xiaoxing People's Hospital and 44 male rectal cancer patients from Guangdong Zhongshan Chenxinghai Hospital between June 2013 and June 2015 were prospectively enrolled. Patients were randomly divided into the trial group receiving arterial infusion with 8 ml of 1% methylene blue and the control group without artery infusion, with 56 cases in each group. All the patients underwent TME. Intra-operational lymph node removal and postoperative urination and sexual function (erection and ejaculation) were compared between two groups. The baseline data of the two groups were not significantly different (all P>0.05). As compared to the control group, the trial group had shorter operation time [(3.28±0.63) hours vs. (4.01±0.94) hours, P<0.01], less blood loss[(92.5±36.4) ml vs. (174.1±61.4) ml, P<0.01], and more lymph nodes harvested per patient (15.8±7.6 vs. 11.9±4.3, P<0.01). One year after operation, classI(, II(, III(, IIII( of urination was observed in 33 cases (58.9%), 15 cases (26.8%), 6 cases (10.7%), 2 cases (3.6%) in the trial group, while 24 (42.9%), 15 (26.8%), 12 (21.4%), 5 (8.9%) in the control group, which indicated that trial group was superior to control group(P<0.05). ClassI(, II(, III( of erection was observed in 36 cases (64.3%), 18 cases (32.1%), 2 cases(3.6%) in the trial group, while 25(44.6%), 23(41.1%), 8(14.3%) in the control group, which indicated that trial group was superior to the control group (P<0.05). ClassI(, II(, III( of ejaculation was found in 36 cases (62.5%), 18 cases (32.1%), 3 cases (5.4%) in the trial group, while 24 (42.9%), 22 (39.3%), 10(17.9%) in the control group, which also indicated that trial group was superior to the control group(P<0

  4. 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.

  5. The effect of continuous low dose methylprednisolone infusion on inflammatory parameters in patients undergoing coronary artery bypass graft surgery: a randomized-controlled clinical trial.

    PubMed

    Ghiasi, Abbas; Shafiee, Akbar; Salehi Omran, Abbas; Ghaffari-Marandi, Neda; Shirzad, Mahmood; Barkhordari, Khosro

    2015-01-01

    This trial was performed to determine if a continuous low-dose infusion of methylprednisolone is as effective as its bolus of high-dose in reducing inflammatory response. The study was single-center, double-blinded randomized clinical trial and performed in a surgical intensive care unit of an academic hospital. In this study, 72 consecutive patients undergoing elective coronary artery bypass grafting (CABG) were assigned to receive either a methylprednisolone loading dose (1mg/kg) followed by continuous infusion (2mg/Kg/24 hours for 1 day) (low-dose regime) or a single dose of methylprednisolone (15 mg/kg) before cardiopulmonary bypass (high dose regime). Serum concentrations of IL-6 and C- reactive protein (CRP) were measured preoperatively and 6, 24 and 48 hours after surgery, and serum creatinine was measured before the operation and 24, 48 and 72 hours postoperatively. The measurements were then compared between the groups to evaluate the efficacy of each regimen. The basic characteristics and measurements were not different between the study groups. There was no significant difference in IL-6 and CRP elevation (P=0.52 and P=0.46, respectively). Early outcomes such as the length of stay in the intensive care unit, intubation time, changes in serum creatinine and blood glucose levels, inotropic support, insulin requirements, and rate of infection were also similar in both groups. A continuous low dose infusion of methylprednisolone was as effective as a single high dose methylprednisolone in reducing the inflammatory response after CABG with extracorporeal circulation with no significant difference in the postoperative measurements and outcomes.

  6. Prospective randomized trial comparing pushable coil and detachable coil during percutaneous implantation of port-catheter system for hepatic artery infusion chemotherapy.

    PubMed

    Park, Sung Ii; Lee, Shin Jae; Lee, Myungsu; Lee, Mu Sook; Kim, Gyoung Min; Kim, Man Deuk; Won, Jong Yun; Lee, Do Yun

    2015-03-01

    The purpose of this study was to prospectively compare the efficacy and controllability of pushable coil and detachable coil during embolization of gastroduodenal artery (GDA) while performing percutaneous implantation of port-catheter system for hepatic artery infusion chemotherapy. Fifty patients (M:F = 42:8, age: 31-81 years) with advanced hepatocellular carcinoma undergoing port-catheter system implantation were randomized into pushable coil group and detachable coil group. During catheter fixation, GDA was embolized as close to the origin as possible. Success rate, number of coils used, number of coils removed due to malposition after deployment, time to occlusion, uncoiled GDA length, pushability, and complications were compared. Pushability was graded as no tension, slight tension, and difficult to advance. Embolization was successful in 49 patients. One failure resulted from repeated regurgitation of pushable coil into hepatic artery. Number of coils used and removed coils, time to occlusion, and uncoiled GDA length were 1-3 (mean 2.32), 5 coils in 3 patients, 4-20 min (mean 8.00), and 0-15.0 mm (mean 3.36) in pushable coil group, and 1-5 (mean 2.12), 2 coils in 2 patients, 2-15 min (mean 7.40), and 0-10.2 mm (mean 2.92) in detachable coil group, respectively, without significant difference. Pushability was no tension (n = 24) and slight tension (n = 1) in pushable coil group and no tension (n = 16), slight tension (n = 7), and difficult to advance (n = 2) in detachable coil group. One hepatic artery dissection occurred in the failed case during coil removal. Pushable coils and detachable coils had similar efficacy and controllability during GDA embolization, although there was a trend favoring detachable coil.

  7. Chemoradiation therapy using radiotherapy, systemic chemotherapy with 5-fluorouracil and nedaplatin, and intra-arterial infusion using carboplatin for locally advanced head and neck cancer - Phase II study.

    PubMed

    Fuwa, Nobukazu; Kodaira, Takesi; Furutani, Kazuhisa; Tachibana, Hiroyuki; Nakamura, Tatsuya; Daimon, Takasi

    2007-11-01

    To improve the treatment results for locally advanced head and neck cancer, chemoradiation therapy by radiotherapy, systemic chemotherapy with 5-fluorouracil (5FU) and nedaplatin (NDP), and intra-arterial therapy using carboplatin (CBDCA) was performed. Thirty-two patients were entered into the study between July 1997 and August 2002. According to the TNM staging (1997), 14 patients had stage III lesions, and 19 patients had stage IV (M0) lesions. Alternating chemoradiotherapy was performed by the following regimen. Initially, systemic chemotherapy was administered, followed by 4 weeks of radiotherapy (36Gy/20 fractions; wide field irradiation) starting 2 days after chemotherapy, a second course of systemic chemotherapy 2 days after radiotherapy, and a second course of a reduced field radiotherapy (30Gy/15 fractions) 2 days after chemotherapy. Arterial injection therapy was administered in the latter half of radiotherapy after the end of the second course of systemic chemotherapy. For systemic chemotherapy, 5FU at 3500mg/m(2)/120h was intravenously administered for 5 days (Days 1-5), and NDP at 120mg/m(2)/6h was administered on Day 6. An intra-arterial agent using CBDCA was continuously infused by a portable electrical pump for 4 (to 6) weeks. The total dose of CBDCA was AUC 6 as established by Calvert's formula. The 5-year local control rate was 59%. The 5-year overall survival rate was 51%. There were no clinically significant adverse effects. Chemoradiation therapy by radiotherapy, systemic chemotherapy, and intra-arterial chemotherapy for locally advanced head and neck cancer may be useful for improving treatment results.

  8. Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report).

    PubMed

    Sawai, Katsuji; Goi, Takanori; Koneri, Kenji; Katayama, Kanji; Yamaguchi, Akio

    2013-08-17

    We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody  + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient's performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.

  9. High dose of green tea infusion normalized spiral artery density in rats treated with the depot-medroxyprogesterone acetate

    PubMed Central

    Emilda, A S; Veri, Nora; Alchalidi, Alchalidi

    2017-01-01

    Aim: The purpose of this study was to investigate the effects of green tea (GT) on the spiral artery density and endometrial thickness in female rats treated with the depot-medroxyprogesterone acetate (DMPA). Material and Methods: A total of 24 female rats were randomly divided into four groups (n = 6 each): The control group (no treatment), the DMPA-treated group, treated with DMPA and GT doses of 165 mg/kg of body weight/day, and treated with DMPA and GT doses of 330 mg/kg of body weight/day. Spiral artery density and endometrial thickness were subjected to histopathological analysis. Results: Spiral artery density decreased in the DMPA-treated group, despite the insignificant difference (P > 0.05). With regard to the administration of GT at doses of 165 and 330 mg/g of body weight/day, only GT at the high dose was capable of significantly preventing a decrease in spiral artery density (P < 0.05). At this dose, the spiral arteries achieved a density comparable to that of the control group (P > 0.05). Meanwhile, the administration of DMPA and/or DMPA with GT did not cause significant changes in endometrial thickness relative to the control group (P > 0.05). Conclusions: DMPA induced a decrease in spiral artery density, despite the insignificant differences, and these changes could be normalized by the administration of high doses of GT. Therefore, GT could be a candidate herb to prevent the adverse effects of the contraceptive DMPA. PMID:28163962

  10. Central venous line complications with chronic ambulatory infusion of prostacyclin analogues in pediatric patients with pulmonary arterial hypertension

    PubMed Central

    Mullen, Mary P.

    2015-01-01

    Abstract Chronic infusion of prostacyclin (PGI2) via a Broviac central venous line (CVL) is attended by risk of CVL-related complications, but we know of only one report regarding CVL-associated bloodstream infection (BSI) with PGI2 in children and none regarding other complications. We conducted a retrospective cohort study involving pediatric patients with pulmonary hypertension treated with chronic intravenous infusion of PGI2 at Boston Children’s Hospital and determined the rate (per 1,000 line-days) of various CVL-related complications. We also determined how often complications necessitated line replacement and hospitalization, time to replacement of CVLs, and interpatient variability in the incidence of complications. From 1999 until 2014, 26 patients meeting follow-up criteria had PGI2 infusion, representing 43,855 line-days; mean follow-up was 56 months (range, 1.4–161 months). The CVL complication rates (per 1,000 line-days) were as follows: CVL-BSI, 0.25; superficial line infection, 0.48; impaired integrity, 0.59; occlusion, 0.09; and malposition, 0.32. The total complication rate was 1.73 cases per 1,000 line-days. All CVL-BSI and malposition cases were treated with CVL removal and replacement. Of CVLs with impaired integrity, 23 could be repaired and 3 required replacement. Six of 21 superficial CVL infections required replacement of the CVL. Three of 4 occluded CVLs were replaced. CVL complications occasioned 65 hospitalizations. There was marked interpatient variability in the rate of complications, much but not all of which appeared to be related to duration of CVL placement. We conclude that non-BSI complications are very significant and that efforts to teach and emphasize other aspects of line care are therefore very important. PMID:26064457

  11. Central venous line complications with chronic ambulatory infusion of prostacyclin analogues in pediatric patients with pulmonary arterial hypertension.

    PubMed

    Marr, Courtney R; McSweeney, Julia E; Mullen, Mary P; Kulik, Thomas J

    2015-06-01

    Chronic infusion of prostacyclin (PGI2) via a Broviac central venous line (CVL) is attended by risk of CVL-related complications, but we know of only one report regarding CVL-associated bloodstream infection (BSI) with PGI2 in children and none regarding other complications. We conducted a retrospective cohort study involving pediatric patients with pulmonary hypertension treated with chronic intravenous infusion of PGI2 at Boston Children's Hospital and determined the rate (per 1,000 line-days) of various CVL-related complications. We also determined how often complications necessitated line replacement and hospitalization, time to replacement of CVLs, and interpatient variability in the incidence of complications. From 1999 until 2014, 26 patients meeting follow-up criteria had PGI2 infusion, representing 43,855 line-days; mean follow-up was 56 months (range, 1.4-161 months). The CVL complication rates (per 1,000 line-days) were as follows: CVL-BSI, 0.25; superficial line infection, 0.48; impaired integrity, 0.59; occlusion, 0.09; and malposition, 0.32. The total complication rate was 1.73 cases per 1,000 line-days. All CVL-BSI and malposition cases were treated with CVL removal and replacement. Of CVLs with impaired integrity, 23 could be repaired and 3 required replacement. Six of 21 superficial CVL infections required replacement of the CVL. Three of 4 occluded CVLs were replaced. CVL complications occasioned 65 hospitalizations. There was marked interpatient variability in the rate of complications, much but not all of which appeared to be related to duration of CVL placement. We conclude that non-BSI complications are very significant and that efforts to teach and emphasize other aspects of line care are therefore very important.

  12. 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.

  13. Tumour growth of colorectal rat liver metastases is inhibited by hepatic arterial infusion of the mTOR-inhibitor temsirolimus after portal branch ligation.

    PubMed

    Sperling, Jens; Ziemann, Christian; Gittler, Anika; Benz-Weißer, Anna; Menger, Michael D; Kollmar, Otto

    2015-04-01

    Portal branch ligation (PBL) can be performed before major hepatic resection of colorectal liver metastases (mCRC) to increase the remnant liver mass. However, PBL may also stimulate mCRC growth through hepatic arterial hyperperfusion and growth factor release. Herein, we studied whether hepatic arterial infusion (HAI) of the mTOR-inhibitor temsirolimus (Tem) is capable of inhibiting the growth of colorectal liver metastases after PBL. WAG/Rij rats were randomized to four groups (n=6 each) and underwent subcapsular implantation of 5×10(5) CC531 cells into the left liver lobe. The animals of two groups underwent simultaneous PBL of the tumour bearing liver lobe. Ten days later animals underwent a HAI either of temsirolimus (Tem and PBL Tem) or saline solution (Sham and PBL Sham). Tumour size was analyzed at days 10 and 13 using three-dimensional ultrasound. In Sham controls tumour volume increased by 43%. After PBL Sham tumour volume increased by 52%. In contrast, in animals undergoing HAI of temsirolimus the tumour growth was not only completely inhibited, but tumour volume was found decreased, irrespective of PBL. After HAI of temsirolimus immunohistochemistry revealed an increased cleaved caspase-3 activity, indicating stimulation of apoptotic cell death. In parallel temsirolimus treatment was associated with a significant reduction of PECAM-1 positive cells within the tumour tissue, implying a reduced tumour vascularisation. HAI of temsirolimus is capable of inhibiting the growth of CC531 colorectal rat liver metastases also after PBL.

  14. Clinical Effectiveness of Intravenous Exenatide Infusion in Perioperative Glycemic Control after Coronary Artery Bypass Graft Surgery: A Phase II/III Randomized Trial.

    PubMed

    Besch, Guillaume; Perrotti, Andrea; Mauny, Frederic; Puyraveau, Marc; Baltres, Maude; Flicoteaux, Guillaume; Salomon du Mont, Lucie; Barrucand, Benoit; Samain, Emmanuel; Chocron, Sidney; Pili-Floury, Sebastien

    2017-08-18

    We aimed to assess the clinical effectiveness of intravenous exenatide compared to insulin in perioperative blood glucose control in coronary artery bypass grafting surgery patients. Patients more than 18 yr old admitted for elective coronary artery bypass grafting were included in a phase II/III nonblinded randomized superiority trial. Current insulin use and creatinine clearance of less than 60 ml/min were exclusion criteria. Two groups were compared: the exenatide group, receiving exenatide (1-h bolus of 0.05 µg/min followed by a constant infusion of 0.025 µg/min), and the control group, receiving insulin therapy. The blood glucose target range was 100 to 139 mg/dl. The primary outcome was the proportion of patients who spent at least 50% of the study period within the target range. The consumption of insulin (Cinsulin) and the time to start insulin (Tinsulin) were compared between the two groups. In total, 53 and 51 patients were included and analyzed in the exenatide and control groups, respectively (age: 70 ± 9 vs. 68 ± 11 yr; diabetes mellitus: 12 [23%] vs. 10 [20%]). The primary outcome was observed in 38 (72%) patients in the exenatide group and in 41 (80%) patients in the control group (odds ratio [95% CI] = 0.85 [0.34 to 2.11]; P = 0.30). Cinsulin was significantly lower (60 [40 to 80] vs. 92 [63 to 121] U, P < 0.001), and Tinsulin was significantly longer (12 [7 to 16] vs. 7 [5 to 10] h, P = 0.02) in the exenatide group. Exenatide alone at the dose used was not enough to achieve adequate blood glucose control in coronary artery bypass grafting patients, but it reduces overall consumption of insulin and increases the time to initiation of insulin.

  15. A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable, advanced hepatocellular carcinoma

    PubMed Central

    Kim, Hee Yeon; Kim, Jin Dong; Park, Jun Yong; Han, Kwang Hyub; Woo, Hyun Young; Choi, Jong Young; Yoon, Seung Kew; Jang, Byoung Kuk; Hwang, Jae Seok; Kim, Sang Gyune; Kim, Young Seok; Seo, Yeon Seok; Yim, Hyung Joon; Um, Soon Ho

    2010-01-01

    Background/Aims Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC. Methods The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks. Results Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group. Conclusions High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC. PMID:21415578

  16. Elevated brain derived neurotrophic factor (BDNF) levels in plasma but not serum reflect in vivo functional viability of infused mesenchymal stem cells after middle cerebral artery occlusion in rat.

    PubMed

    Nakamura, Hideyuki; Sasaki, Yuichi; Sasaki, Masanori; Kataoka-Sasaki, Yuko; Oka, Shinichi; Nakazaki, Masahito; Namioka, Takahiro; Namioka, Ai; Onodera, Rie; Suzuki, Junpei; Nagahama, Hiroshi; Mikami, Takeshi; Wanibuchi, Masahiko; Kocsis, Jeffery D; Honmou, Osamu

    2017-02-08

    Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow elicits functional recovery in rat stroke models and clinical studies in patients are ongoing. Brain derived neurotrophic factor (BDNF) is a neurotrophic factor produced by MSCs and may contribute to their therapeutic efficacy. The purpose of the current study was to determine if BDNF is elevated in infarcted brain and in which compartment of blood (plasma or serum) after intravenous MSC infusion in a middle cerebral artery occlusion (MCAO) model in the rat. In rats, a permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament and MSCs were intravenously administered 6 h after right MCAO induction. Enzyme-linked immunosorbent assay (ELISA) analysis of brain, serum and plasma BDNF were performed after the MSC infusion following the MCAO induction. Lesion volume was assessed using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. Infused MSCs reduced lesion volume and elicited functional improvement compared to the vehicle infused group. ELISA analysis of the MSC treated group revealed an increase BDNF levels in the infarcted hemisphere of the brain and plasma, but not in serum. The MSC group showed a greater increase in BDNF levels than sham control. In the MSC group, the expression of increased plasma BDNF levels correlated with increased brain BDNF levels. These results support the hypothesis that BDNF levels in plasma, but not serum, may be more appropriate to detect circulating BDNF in vivo following MSC infusion in a cerebral infarction rat model of ischemic stroke. Further, plasma BDNF might reflect in vivo functional viability of infused MSCs after stroke.

  17. 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.

  18. Early Detection of Therapeutic Response to Hepatic Arterial Infusion Chemotherapy of Liver Metastases from Colorectal Cancer Using Diffusion-Weighted MR Imaging

    SciTech Connect

    Marugami, Nagaaki; Tanaka, Toshihiro Kitano, Satoru; Hirohashi, Shinji; Nishiofuku, Hideyuki; Takahashi, Aki; Sakaguchi, Hiroshi; Matsuoka, Masaki; Otsuji, Toshio; Takahama, Junko; Higashiura, Wataru; Kichikawa, Kimihiko

    2009-07-15

    The purpose of this study was to investigate whether diffusion-weighted magnetic resonance imaging (DWI) is useful for early detection of the response of hepatic colorectal metastases to hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil (5-FU). The subjects were 12 patients with hepatic colorectal metastases. The indwelling catheter for HAIC was placed in the hepatic artery, and 1000 mg/m{sup 2} 5-FU was given repeatedly once a week. DWI was performed before and 9 days after HAIC. The minimum and mean apparent diffusion coefficient (ADC) values (minADC and meanADC) were measured. The relative change in ADC values (%ADC) and the relative change in tumor size on follow-up CT after 3 months (reduction ratio) were determined. Liver metastases were divided into two groups, responder and nonresponder. The correlation between %ADC and reduction ratio was determined, and %ADC was compared between the two groups. Eleven patients successfully completed HAIC over the 3-month period; 48 metastatic lesions were evaluated. Positive correlations were observed for relative change between %minADC and reduction ratio (r = 0.709) and between %meanADC and reduction ratio (r = 0.536). Both %minADC and %meanADC were significantly greater in the responder group than in the nonresponder group. With the threshold determined as < 3.5%, the receiver-operating curve analysis showed higher sensitivity and specificity values for %minADC (100% and 92.6%, respectively) than for %meanADC (66.7% and 74.1%, respectively). In conclusion, the relative change in minimum ADC values on DWI may be useful for early detection of the response of liver metastases to HAIC with 5-FU.

  19. 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.

  20. 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

  1. Hepatic intra-arterial infusion of yttrium-90 microspheres in the treatment of recurrent hepatocellular carcinoma after liver transplantation: A case report

    PubMed Central

    Rivera, Louis; Giap, Huan; Miller, William; Fisher, Jonathan; Hillebrand, Donald J; Marsh, Christopher; Schaffer, Randolph L

    2006-01-01

    Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemo-embolization (TACE), radiofrequency ablation (RFA), ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences of initial treatment. PMID:17007031

  2. Hepatic intra-arterial infusion of yttrium-90 microspheres in the treatment of recurrent hepatocellular carcinoma after liver transplantation: a case report.

    PubMed

    Rivera, Louis; Giap, Huan; Miller, William; Fisher, Jonathan; Hillebrand, Donald J; Marsh, Christopher; Schaffer, Randolph L

    2006-09-21

    Hepatocellular carcinoma (HCC) recurs with a reported frequency of 12%-18% after liver transplantation. Recurrence is associated with a mortality rate exceeding 75%. Approximately one-third of recurrences develop in the transplanted liver and are therefore amenable to local therapy. A variety of treatment modalities have been reported including resection, transarterial chemo-embolization (TACE), radiofrequency ablation (RFA), ethanol ablation, cryoablation, and external beam irradiation. Goals of treatment are tumor control and the minimization of toxic effect to functional parenchyma. Efficacy of treatment is mitigated by the need for ongoing immunosuppression. Yttrium-90 microspheres have been used as a treatment modality both for primary HCC and for pre-transplant management of HCC with promising results. Twenty-two months after liver transplantation for hepatitis C cirrhosis complicated by HCC, a 42-year old man developed recurrence of HCC in his transplant allograft. Treatment of multiple right lobe lesions with anatomic resection and adjuvant chemotherapy was unsuccessful. Multifocal recurrence in the remaining liver allograft was treated with hepatic intra-arterial infusion of yttrium-90 microspheres (SIR-Spheres, Sirtex Medical Inc., Lake Forest, IL, USA). Efficacy was demonstrated by tumor necrosis on imaging and a decrease in alpha-fetoprotein (AFP) level. There were no adverse consequences of initial treatment.

  3. Adsorption properties for urokinase on local diatomite surface

    NASA Astrophysics Data System (ADS)

    Yang, Yuxiang; Zhang, Jianbo; Yang, Weimin; Wu, Jieda; Chen, Rongsan

    2003-02-01

    In this paper, adsorption isotherm of urokinase on two typical local diatomites were determined at 25 °C and their surface electrical potentials (ζ), isoelectrical point values (IEP) were determined. The properties of diatomites, the relationship among diatomite structure, pore-size distribution, surface ζ and adsorption isotherm were discussed. The adsorption equation of urokinase was calculated from the adsorption isotherm. The adsorption mode of urokinase on diatomite surface was judged by the configuration function α. The relationship between the amount of adsorbed urokinase and IEP value was also discussed.

  4. Feasibility of continuous, catheter-directed thrombolysis using low-dose urokinase in combination with low molecular-weight heparin for acute iliofemoral venous thrombosis in patients at risk of bleeding

    PubMed Central

    Chen, Guoping; Shi, Wangyin; He, Xu; Lou, Wensheng; Chen, Liang; Gu, Jianping

    2017-01-01

    The present study aimed to examine the feasibility of catheter-directed thrombolysis (CDT) using continuous infusion of low-dose urokinase in combination with low molecular weight heparin (LMWH) for acute iliofemoral venous thrombosis. This retrospective analysis included patients with symptomatic acute iliofemoral venous thrombosis who received CDT using continuous infusion of low-dose urokinase in combination with LMWH within the past four years. Urokinase was administered at 1×104 U/h and 2×104 U/h in patients at high-risk and low-risk of bleeding, respectively. Measurements included urokinase dosage, duration, clinical outcomes and CDT-related complications. A total of 46 patients were included (high-risk, n=17; low-risk, n=29). In the high-risk patients, 64.7% experienced dissolution of ≥50% thrombi after a median CDT duration of 8 days (range, 6–10 days) and median total urokinase dose of 1.92×106 units (range, 1.44–2.4×106 units). In the low-risk patients, 82.8% achieved dissolution of ≥50% thrombi after a median CDT duration of 7 days (range, 4–10 days) and a median total urokinase dose of 3.36×106 units (range, 1.92–4.80×106 units). Remission of clinical symptoms after CDT was achieved in 15 (88.2%) and 28 (96.6%) cases in high-risk and low-risk patients, respectively. No treatment-associated pulmonary embolism or major bleeding was observed. Three (6.5%) subjects (high-risk, n=1; low-risk, n=2) experienced minor bleeding. In conclusion, continuous infusion of low-dose urokinase via CDT in combination with LMWH is effective and safe for acute iliofemoral venous thrombosis in patients with one or more risk factor for bleeding. PMID:28352362

  5. 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.

  6. Evaluation of Intrahepatic Perfusion on Fusion Imaging Using a Combined CT/SPECT System: Influence of Anatomic Variations on Hemodynamic Modification Before Installation of Implantable Port Systems for Hepatic Arterial Infusion Chemotherapy

    SciTech Connect

    Ikeda, Osamu Tamura, Yoshitaka; Nakasone, Yutaka; Shiraishi, Shinya; Kawanaka, Kouichi; Tomiguchi, Seiji; Takamori, Hiroshi; Chikamoto, Akira; Kanemitsu, Keiichirou; Yamashita, Yasuyuki

    2007-06-15

    Background. In some patients with hepatic tumors, anatomic variations in the hepatic arteries may require hemodynamic modification to render effective hepatic arterial infusion chemotherapy delivered via implantable port systems. We used a combined CT/SPECT system to obtain fused images of the intrahepatic perfusion patterns in patients with such anatomic variations and assessed their effects on the treatment response of hepatic tumors. Methods. Using a combined SPECT/CT system, we obtained fused images in 110 patients with malignant liver tumors (n = 75) or liver metastasis from unresectable pancreatic cancer (n = 35). Patients with anatomic hepatic arteries variations underwent hemodynamic modification before the placement of implantable port systems for hepatic arterial infusion chemotherapy. We evaluated their intrahepatic perfusion patterns and the initial treatment response of their liver tumors. The perfusion patterns on the fused images were classified as homogeneous, local hypoperfusion, and/or perfusion defect. Using the WHO criteria of complete response (CR), partial response (PR), no change (NC), and progressive disease (PD), we evaluated the patients' tumor responses after 3 months on multislice helical CT scans. The treatment was regarded as effective in patients who achieved a complete response or partial response. Results. Anatomic hepatic artery variations were present in 15 of the 110 patients (13.6%); 5 manifested replacement of the left hepatic artery (LHA), 8 of the right hepatic artery (RHA), and 1 each had replacement of the RHA and LHA, and replacement of the LHA plus an accessory RHA. In 13 of these 15 patients (87%), occlusion with metallic coils was successful. On fusion imaging, the perfusion patterns were recorded as homogeneous in 6 patients (43%), as hypoperfusion in 7 (50%), and 1 patient had a perfusion defect (7.1%) in the embolized arterial region. Of the 8 patients with RHA replacement, 4 manifested a homogeneous distribution and

  7. [A case report-advanced pancreas cancer with liver and lung metastases well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting].

    PubMed

    Hasuike, Yasunori; Tanigawa, Takahiko; Yamada, Masaharu; Minami, Yukiko; Ezumi, Koji; Kashiwazaki, Masaki; Fujimoto, Takayoshi

    2008-11-01

    We report a case of advanced pancreatic cancer with liver and lung metastases that was well controlled over one year by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion in an outpatient setting. The patient was a 74-year-old woman. Chief complaints were back pain and anorexia. She was diagnosed with pancreas cancer with liver and lung metastases at the time of first visit. We started systemic chemotherapy with gemcitabine 1 g/body and 5-FU 1 g/body alternately every other week on an outpatient basis. At 1.5 months (M) after initiation of chemotherapy, we started radiation therapy to the main tumor at a total dose of 40 Gy. After radiation, chemotherapy was resumed. As a result, the size of the main tumor decreased but metastatic liver tumors got larger. Then we changed to combination therapy with systemic chemotherapy (gemcitabine and 5-FU) and hepatic arterial infusion (5-FU weekly). Liver metastases almost disappeared after 7.5 M. Despite all these treatments, however, the number of metastatic lung tumors increased. The patient was hospitalized for 15 M and died after 17 M. We focused on and succeeded in the prolongation of lifetime and maintenance of QOL by combination therapy with systemic chemotherapy, radiation and hepatic arterial infusion therapy.

  8. Early pulmonary response is critical for extra-pulmonary carbon nanoparticle mediated effects: comparison of inhalation versus intra-arterial infusion exposures in mice.

    PubMed

    Ganguly, Koustav; Ettehadieh, Dariusch; Upadhyay, Swapna; Takenaka, Shinji; Adler, Thure; Karg, Erwin; Krombach, Fritz; Kreyling, Wolfgang G; Schulz, Holger; Schmid, Otmar; Stoeger, Tobias

    2017-06-20

    The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM. Equivalent surface area CNP doses in the blood (30mm(2) per animal) were applied by IAI or inhalation (lung-deposited dose 10,000mm(2); accounting for 0.3% of lung-to-blood CNP translocation). Mice were analyzed for changes in hematology and molecular markers of endothelial/epithelial dysfunction, pro-inflammatory reactions, oxidative stress, and coagulation in lungs and extra-pulmonary organs after CNP inhalation (4 h and 24 h) and CNP infusion (4 h). For methodological reasons, we used two different CNP types (spark-discharge and Printex90), with very similar physicochemical properties [≥98 and ≥95% elemental carbon; 10 and 14 nm primary particle diameter; and 800 and 300 m(2)/g specific surface area] for inhalation and IAI respectively. Mild pulmonary inflammatory responses and significant systemic effects were observed following 4 h and 24 h CNP inhalation. Increased retention of activated leukocytes, secondary thrombocytosis, and pro-inflammatory responses in secondary organs were detected following 4 h and 24 h of CNP inhalation only. Interestingly, among the investigated extra-pulmonary tissues (i.e. aorta, heart, and liver); aorta revealed as the most susceptible extra-pulmonary target following inhalation exposure. Bypassing the lungs by IAI however did not induce any extra-pulmonary effects at 4 h as compared to inhalation. Our findings indicate that extra-pulmonary effects due to CNP

  9. 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

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

    2015-01-01

    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. 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. 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 stomach and phlebitis. No

  10. 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

  11. 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.

  12. Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies

    PubMed Central

    Pingpank, James F.; Libutti, Steven K.; Chang, Richard; Wood, Bradford J.; Neeman, Ziv; Kam, Anthony W.; Figg, William D.; Zhai, Souping; Beresneva, Tatiana; Seidel, Geoffrey D.; Alexander, H. Richard

    2008-01-01

    Purpose We conducted a phase I study of a 30-minute hepatic artery infusion of melphalan via a percutaneously placed catheter and hepatic venous hemofiltration using a double balloon catheter positioned in the retrohepatic inferior vena cava to shunt hepatic venous effluent through an activated charcoal filter and then to the systemic circulation. The purpose of the study was to demonstrate feasibility in an initial cohort and subsequently determine the maximum tolerated dose and dose-limiting toxicity of melphalan. Patients and Methods The initial cohort (n = 12) was treated with 2.0 mg/kg of melphalan before dose escalation to 3.5 mg/kg (n = 16). Total hepatic drug delivery, systemic levels, and percent filter efficiency were determined. Patients were assessed for hepatic and systemic toxicity and response. Results A total of 74 treatments were administered to 28 patients. Twelve patients with primary and metastatic hepatic tumors received 30 treatments (mean, 2.5 per patient) at an initial melphalan dose of 2.0 mg/kg. At 3.5 mg/kg, a dose-limiting toxicity (neutropenia and/or thrombocytopenia) was observed in two of six patients. Transient grade 3/4 hepatic and systemic toxicity was seen after 19% and 66% of treatments, respectively. An overall radiographic response rate of 30% was observed in treated patients. In the 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses. Conclusion Delivery of melphalan via this system is feasible, with limited, manageable toxicity and evidence of substantial antitumor activity; 3 mg/kg is the maximum safe tolerated dose of melphalan administered via this technique. PMID:15908655

  13. Hepatic arterial infusion chemotherapy using fluorouracil, epirubicin, and mitomycin C for patients with liver metastases from gastric cancer after treatment failure of systemic S-1 plus cisplatin.

    PubMed

    Seki, Hiroshi; Ohi, Hiroyuki; Ozaki, Toshirou; Yabusaki, Hiroshi

    2016-07-01

    For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression. To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin. We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m(2) weekly), epirubicin (30 or 40 mg/m(2) every 4 weeks), and mitomycin C (2.7 mg/m(2) biweekly). Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months. Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC. © The Foundation Acta Radiologica 2015.

  14. Pharmacogenetic determinants of outcomes on triplet hepatic artery infusion and intravenous cetuximab for liver metastases from colorectal cancer (European trial OPTILIV, NCT00852228).

    PubMed

    Lévi, Francis; Karaboué, Abdoulaye; Saffroy, Raphaël; Desterke, Christophe; Boige, Valerie; Smith, Denis; Hebbar, Mohamed; Innominato, Pasquale; Taieb, Julien; Carvalho, Carlos; Guimbaud, Rosine; Focan, Christian; Bouchahda, Mohamed; Adam, René; Ducreux, Michel; Milano, Gérard; Lemoine, Antoinette

    2017-08-17

    The hepatic artery infusion (HAI) of irinotecan, oxaliplatin and 5-fluorouracil with intravenous cetuximab achieved outstanding efficacy in previously treated patients with initially unresectable liver metastases from colorectal cancer. This planned study aimed at the identification of pharmacogenetic predictors of outcomes. Circulating mononuclear cells were analysed for 207 single-nucleotide polymorphisms (SNPs) from 34 pharmacology genes. Single-nucleotide polymorphisms passing stringent Hardy-Weinberg equilibrium test were tested for their association with outcomes in 52 patients (male/female, 36/16; WHO PS, 0-1). VKORC1 SNPs (rs9923231 and rs9934438) were associated with early and objective responses, and survival. For rs9923231, T/T achieved more early responses than C/T (50% vs 5%, P=0.029) and greatest 4-year survival (46% vs 0%, P=0.006). N-acetyltransferase-2 (rs1041983 and rs1801280) were associated with up to seven-fold more macroscopically complete hepatectomies. Progression-free survival was largest in ABCB1 rs1045642 T/T (P=0.026) and rs2032582 T/T (P=0.035). Associations were found between toxicities and gene variants (P<0.05), including neutropenia with ABCB1 (rs1045642) and SLC0B3 (rs4149117 and rs7311358); and diarrhoea with CYP2C9 (rs1057910), CYP2C19 (rs3758581), UGT1A6 (rs4124874) and SLC22A1 (rs72552763). VKORC1, NAT2 and ABCB1 variants predicted for HAI efficacy. Pharmacogenetics could guide the personalisation of liver-targeted medico-surgical therapies.British Journal of Cancer advance online publication, 17 August 2017; doi:10.1038/bjc.2017.278 www.bjcancer.com.

  15. 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

  16. Characterization of a specific anti-human urokinase antibody: Development of a sensitive competition radioimmunoassay for urokinase antigen

    SciTech Connect

    Huber, K.; Kirchheimer, J.; Binder, B.R.

    1984-05-01

    Specific inhibiting IgG antibodies were raised in a rabbit using purified human high molecular weight urokinase as antigen. The antibodies reacted with both high molecular weight and low molecular weight human urokinase using an Ouchterlony double-immunodiffusion technique in such a way that one line of complete identity was obtained. Neither precipitation nor functional inhibition was observed for the tissue-type plasminogen activator. Kinetic studies with plasminogen as a natural high molecular weight substrate or the synthetic low molecular weight p-nitroanilide substrate pyro-Glu-Gly-Arg-pNA revealed, for both substrates, mainly a competitive type of inhibition for the Fab fragments of the specific anti-urokinase antibodies. This characterized anti-urokinase IgG was employed to develop a competitive radioimmunoassay, for human urokinase with /sup 125/I-labeled urokinase as tracer. In this radioimmunoassay, the lower detection limit for urokinase antigen was 10 pg/ml sample; the intrassay variation was 2.8%, and the interassay variation was 5.3%. Applying this radioimmunoassay to plasma samples obtained from healthy young volunteers, urokinase antigen could be measured in a concentration of 7.82 +/- 3.97 ng/ml for mean and 6.66 +/- 2.39 ng/ml for women (mean +/- SD).

  17. Regulatory Effects of Urokinase on Mesenchymal Stromal Cell Migration, Proliferation, and Matrix Metalloproteinase Secretion.

    PubMed

    Beloglazova, I B; Zubkova, E S; Tsokolaeva, Z I; Stafeev, Yu S; Dergilev, K V; Ratner, E I; Shestakova, M V; Sukhareva, O Yu; Parfenova, E V; Men'shikov, M Yu

    2016-10-01

    We studied the effect of urokinase, its recombinant forms, and domain fragments on migration and proliferation of adipose tissue mesenchymal stromal cells (MSCs) and MMP secretion by these cells. Urokinase, but not its recombinant forms, slightly induced directed migration of MSCs. Spontaneous migration of MSCs increased under the action of urokinase or its isolated kringle domain. Migration induced by platelet-derived growth factor was inhibited by proteolytically inactive form of urokinase, the kringle domain, and blocking antibody to urokinase receptor. Urokinase, its proteolytically inactive form, and kringle domain produced no effect on MSC proliferation. In contrast to platelet-derived growth factor, all urokinase forms induced secretion of MMP-9 by MSCs.

  18. Construction of a BALB/c-Nu Mouse Model of Invasive Bladder Carcinoma and Preliminary Studies on the Treatment of Bladder Tumors through Internal Iliac Arterial Infusion of Albumin-Bound Arsenic Trioxide (As2O3)

    PubMed Central

    Li, Qiaoxing; Wang, Weilu; Shen, Xiangqian; Liu, Hua; Liu, Ruijiang

    2015-01-01

    To establish a BALB/c-nu mouse model of invasive bladder carcinoma and to investigate the feasibility, efficacy, and side effects of treating the mouse xenografts with internal iliac arterial infusion of albumin-bound arsenic trioxide (As2O3). Bladder tumors were established by intravesicular injection. Color Doppler were used to monitor tumor growth. Albumin-bound As2O3 and bovine serum albumin (BSA) nanoparticles were synthesized by cross-linking. BALB/c-nu mice were randomly divided into four treatment groups: 1) normal saline, 2) BSA nanoparticles, 3) As2O3 injections, and 4) albumin-bound As2O3. In an attempt to replicate the treatment of bladder cancer in humans using internal iliac arterial infusion, the drugs were injected into the mouse abdominal aorta. Tumor xenografts were established successfully. Mice treated with As2O3 injections and with albumin-bound As2O3 had significantly smaller bladders (36.59% and 37.82% smaller, respectively) than mice given normal saline injections (P < 0.01). Mice receiving As2O3 injections had lower white blood cell (WBC) and platelet counts compared with mice receiving normal saline injections only (P < 0.05). However, mice treated with albumin-bound As2O3 did not experience a significant decrease in WBC or platelet counts compared with control mice. A model of intra-arterial bladder cancer treatment was successfully established in BALB/c-nu mice. In this model, albumin-bound As2O3 appeared to be an effective method for treating bladder tumors, with less severe hematologic side effects compared with As2O3 alone. The infusion of albumin-bound As2O3 through the internal iliac artery is a promising method of bladder cancer therapy. PMID:25915411

  19. Transgenic chickens expressing human urokinase-type plasminogen activator.

    PubMed

    Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

    2013-09-01

    Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P < 0.05). The expression of huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P < 0.05). Furthermore, adult transgenic rooster showed reduced (P < 0.05) fertility, as revealed by reduced volume of semen ejaculate, sperm concentration, and sperm viability. Taken together, our data suggest that huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

  20. Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration.

    PubMed

    Kapustin, Alexander; Stepanova, Victoria; Aniol, Natalia; Cines, Douglas B; Poliakov, Alexei; Yarovoi, Serge; Lebedeva, Tatiana; Wait, Robin; Ryzhakov, Grigory; Parfyonova, Yelena; Gursky, Yaroslav; Yanagisawa, Hiromi; Minashkin, Mikhail; Beabealashvilli, Robert; Vorotnikov, Alexander; Bobik, Alex; Tkachuk, Vsevolod

    2012-04-15

    uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5-/-) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (Fbln(RGE/RGE) MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+-binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility.

  1. Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated β1-integrin-dependent cell migration

    PubMed Central

    Kapustin, Alexander; Stepanova, Victoria; Aniol, Natalia; Cines, Douglas B.; Poliakov, Alexei; Yarovoi, Serge; Lebedeva, Tatiana; Wait, Robin; Ryzhakov, Grigory; Parfyonova, Yelena; Gursky, Yaroslav; Yanagisawa, Hiromi; Minashkin, Mikhail; Beabealashvilli, Robert; Vorotnikov, Alexander; Bobik, Alex; Tkachuk, Vsevolod

    2015-01-01

    uPA (urokinase-type plasminogen activator) stimulates cell migration through multiple pathways, including formation of plasmin and extracellular metalloproteinases, and binding to the uPAR (uPA receptor; also known as CD87), integrins and LRP1 (low-density lipoprotein receptor-related protein 1) which activate intracellular signalling pathways. In the present paper we report that uPA-mediated cell migration requires an interaction with fibulin-5. uPA stimulates migration of wild-type MEFs (mouse embryonic fibroblasts) (Fbln5+/+ MEFs), but has no effect on fibulin-5-deficient (Fbln5−/−) MEFs. Migration of MEFs in response to uPA requires an interaction of fibulin-5 with integrins, as MEFs expressing a mutant fibulin-5 incapable of binding integrins (FblnRGE/RGE MEFs) do not migrate in response to uPA. Moreover, a blocking anti-(human β1-integrin) antibody inhibited the migration of PASMCs (pulmonary arterial smooth muscle cells) in response to uPA. Binding of uPA to fibulin-5 generates plasmin, which excises the integrin-binding N-terminal cbEGF (Ca2+ -binding epidermal growth factor)-like domain, leading to loss of β1-integrin binding. We suggest that uPA promotes cell migration by binding to fibulin-5, initiating its cleavage by plasmin, which leads to its dissociation from β1-integrin and thereby unblocks the capacity of integrin to facilitate cell motility. PMID:22280367

  2. Impact of Intraoperative Continuous-Infusion Versus Intermittent Dosing of Cefazolin Therapy on the Incidence of Surgical Site Infections After Coronary Artery Bypass Grafting.

    PubMed

    Shoulders, Bethany R; Crow, Jessica R; Davis, Stephanie L; Whitman, Glenn J; Gavin, Melanie; Lester, Laeban; Barodka, Viachaslau; Dzintars, Kathryn

    2016-02-01

    To determine whether intraoperative continuous-infusion (CI) cefazolin reduces the incidence of surgical site infections (SSIs) compared with intermittent (INT) cefazolin dosing in patients undergoing coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB); safety end points and protocol adherence comparing the two dosing strategies were also explored. Retrospective quasi-experimental (pre-post intervention) cohort study. Large academic medical center. A total of 516 adults who underwent CABG on CPB and received cefazolin intraoperatively between June 1, 2013, and December 31, 2014, were included. The INT cohort included 284 patients who underwent CABG from June 2013 to February 2014. The CI cohort included 232 patients who underwent CABG from April to December 2014, after an intraoperative CI cefazolin protocol for cardiac surgery patients undergoing CPB was adopted in March 2014. The primary end point was incidence of SSIs, and safety end points of renal dysfunction and seizures were evaluated. Multivariable logistic regression analysis was used to determine the impact on SSIs when controlling for other risk factors. A subgroup analysis for this study included 2 months within each time period to evaluate protocol adherence. The overall incidence of SSIs was decreased in patients receiving CI cefazolin, although this did not reach statistical significance (4.6% in the INT cohort vs 1.7% in the CI cohort, p=0.116). Superficial SSIs were significantly reduced in the CI cohort (2.8% in the INT cohort vs 0.4% in the CI cohort, p=0.039). In the regression analysis, CI cefazolin decreased the odds of SSI by 66%, although it did not reach statistical significance (p=0.077). Safety end points were not significantly different between groups. Overall protocol adherence did not differ significantly between the cohorts: 77% in the INT cohort and 67% in the CI cohort (p=0.212). CI cefazolin significantly decreased the incidence of superficial SSIs compared with

  3. Continuous postoperative insulin infusion reduces deep sternal wound infection in patients with diabetes undergoing coronary artery bypass grafting using bilateral internal mammary artery grafts: a propensity-matched analysis.

    PubMed

    Ogawa, Shinji; Okawa, Yasuhide; Sawada, Koshi; Goto, Yoshihiro; Yamamoto, Masanori; Koyama, Yutaka; Baba, Hiroshi; Suzuki, Takahiko

    2016-02-01

    Deep sternal wound infection (DSWI), especially in patients with diabetes mellitus (DM), is a major concern after coronary artery bypass grafting (CABG) with bilateral internal mammary artery (BIMA) grafts. We evaluated the risk of DSWI and other clinical outcomes between continuous insulin infusion therapy (CIT) and insulin sliding scale therapy (IST) in a cohort of DM patients who underwent CABG with BIMA. The clinical records of DM patients who underwent isolated CABG with BIMA were retrospectively reviewed. The study population consisted of 95 patients who received CIT and 126 patients who received IST. Furthermore, a one-to-one matched analysis based on estimated propensity scores for patients who received CIT or IST yielded two groups comprising 58 patients each. The proportion of patients with DSWI, overall survival rates and major adverse cardiac events were compared between the two groups in the overall and the propensity-matching cohort. The prevalence of DSWI requiring debridement and closure was significantly reduced in the CIT group compared with that in the IST group [1/95 (1.1%) vs 9/126 (7.1%), P = 0.031]; these results were not attenuated even after propensity-matching analysis [0/58 (0%) vs 6/58 (10.3%), P = 0.031]. The mean preoperative glucose levels were similar between the two groups (157.5 ± 54.6 vs 176.1 ± ±70 mg/dl, P = 0.063), whereas the mean glucose values were significantly lower on the first and second operative days in the CIT group than in the IST group (132.9 ± 44.1 vs 197.8 ± 78.6 mg/dl, P < 0.0001; 153.5 ± 58.8 vs 199.6 ± 89.1 mg/dl, P < 0.0001, respectively). The glucose variability levels within 24 h postoperatively were significantly higher in the IST group (46.1 ± 19.4 vs 66.4 ± 26.8 mg/dl, P < 0.0001). The 30-day and 1-year survival rates were similar between the two groups (100 vs 99.2%, P = 0.384; 96.6 vs 94.4%, P = 0.454). No results were changed in the propensity-matching models. The CIT approach reduced the

  4. The Effect of Prophylactic Phenylephrine and Ephedrine Infusions on Umbilical Artery Blood pH in Women With Preeclampsia Undergoing Cesarean Delivery With Spinal Anesthesia: A Randomized, Double-Blind Trial.

    PubMed

    Higgins, Nicole; Fitzgerald, Paul C; van Dyk, Dominique; Dyer, Robert A; Rodriguez, Natalie; McCarthy, Robert J; Wong, Cynthia A

    2017-09-25

    Spinal anesthesia for cesarean delivery is associated with a high incidence of hypotension. Phenylephrine results in higher umbilical artery pH than ephedrine when used to prevent or treat hypotension in healthy women. We hypothesized that phenylephrine compared to ephedrine would result in higher umbilical artery pH in women with preeclampsia undergoing cesarean delivery with spinal anesthesia. This study was a randomized double-blind clinical trial. Nonlaboring women with preeclampsia scheduled for cesarean delivery with spinal anesthesia at Prentice Women's Hospital of Northwestern Medicine were randomized to receive prophylactic infusions of phenylephrine or ephedrine titrated to maintain systolic blood pressure >80% of baseline. Spinal anesthesia consisted of hyperbaric 0.75% bupivacaine 12 mg, fentanyl 15 µg, and morphine 150 µg. The primary outcome was umbilical arterial blood pH and the secondary outcome was umbilical artery base excess. One hundred ten women were enrolled in the study and 54 per group were included in the analysis. There were 74 and 72 infants delivered in the ephedrine and phenylephrine groups, respectively. The phenylephrine:ephedrine ratio for umbilical artery pH was 1.002 (95% confidence interval [CI], 0.997-1.007). Mean [standard deviation] umbilical artery pH was not different between the ephedrine 7.20 [0.10] and phenylephrine 7.22 [0.07] groups (mean difference -0.02, 95% CI of the difference -0.06 to 0.07; P = .38). Median (first, third quartiles) umbilical artery base excess was -3.4 mEq/L (-5.7 to -2.0 mEq/L) in the ephedrine group and -2.8 mEq/L (-4.6 to -2.2mEq/L) in the phenylephrine group (difference -0.6 mEq/L, 95% CI of the difference -1.6 to 0.3 mEq/L; P = .10). When adjusted for gestational age and infant gender, umbilical artery pH did not differ between groups. There were also no differences in the umbilical artery pH stratified by magnesium therapy or by the severity of preeclampsia. We were unable to demonstrate a

  5. [A case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after standard chemotherapy failure].

    PubMed

    Osawa, Gakuji; Yoshimatsu, Kazuhiko; Yokomizo, Hajime; Otani, Taisuke; Yano, Yuki; Itagaki, Hiroko; Matsumoto, Atsuo; Fujimoto, Takashi; Umehara, Arihiro; Ogawa, Kenji

    2010-11-01

    We report a case of multiple lung and liver metastases from colon cancer treated with clinical benefit by hepatic arterial infusion chemotherapy plus cetuximab mono-therapy after a standard chemotherapy was failed. A 61-year-old female who had sigmoid colon cancer with unresectable multiple lung and liver metastases underwent sigmoidectomy. Bevacizumab plus mFOLFOX6 was performed as first-line therapy. Partial response was obtained temporarily. After the first-line therapy failed, bevacizumab plus FOLFIRI as second-line, and cetuximab plus CPT-11 as third-line therapy were performed. Since these regimens did not work, her performance status got worse by cholangitis due to progressive liver metastases and anemia. Hepatic arterial infusion chemotherapy for liver metastases and cetuximab for lung metastases as fourth therapy were chosen because we thought her liver metastases should be critical for the maintenance of her QOL and diagnosis. After that, serum CEA was reduced from 14,715 to 6,940 ng/mL during the 3 month period. And her performance status got better as cholongitis and anemia were improved. Additionally, lung metastases were controlled by cetuximab.

  6. Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

    PubMed

    Kieninger, Martin; Flessa, Julia; Lindenberg, Nicole; Bele, Sylvia; Redel, Andreas; Schneiker, André; Schuierer, Gerhard; Wendl, Christina; Graf, Bernhard; Silbereisen, Vera

    2017-07-06

    Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation

  7. 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.

  8. Combination treatment of biomechanical support and targeted intra-arterial infusion of peripheral blood stem cells mobilized by granulocyte-colony stimulating factor for the osteonecrosis of the femoral head: a randomized controlled clinical trial.

    PubMed

    Mao, Qiang; Wang, Weidong; Xu, Taotao; Zhang, Shanxing; Xiao, Luwei; Chen, Di; Jin, Hongting; Tong, Peijian

    2015-04-01

    The objective of this study was to determine the benefits of combination treatment with mechanical support and targeted intra-arterial infusion of peripheral blood stem cells (PBSCs) mobilized by granulocyte-colony stimulating factor (G-CSF) via the medial circumflex femoral artery on the progression of osteonecrosis of the femoral head (ONFH). Fifty-five patients (89 hips) with early and intermediate stage ONFH were recruited and randomly assigned to combination treatment or mechanical support treatment (control group). All hips received mechanical support treatment (porous tantalum rod implantation). Then, hips in the combination treatment group were performed targeted intra-arterial infusion of PBSCs. At each follow-up, Harris hip score (HHS) and Association Research Circulation Osseous (ARCO) classification were used to evaluate the symptoms and progression of osteonecrosis. Total hip arthroplasty (THA) was assessed as an endpoint at each follow-up. At 36 months, 9 of the 41 hips (21.95%) in the control group progressed to clinical failure and underwent THA whereas only 3 of the 48 hips (6.25%) in the combination treatment group required THA (p = 0.031). Kaplan-Meier survival analysis showed a significant difference in the survival time between the two groups (log-rank test; p = 0.025). Compared to the control group, combination treatment significantly improved the HHS at 36 months (p = 0.003). At the final follow-up examination, radiological progression was noted in 13 of 41 hips (31.71%) for the control group, but in only 4 of 48 hips (8.33%) for the combination treatment group (p = 0.005). The overall collapse rates were 15.15% (5/33 hips) and 8.11% (3/37 hips) in the control and combination treatment groups, respectively. Targeted intra-arterial infusion of PBSCs is capable of enhancing the efficacy of biomechanical support in the treatment of ONFH. This clinical trial confirmed that the combination treatment might be a safe and feasible

  9. Production and purification of urokinase: a comprehensive review.

    PubMed

    Bansal, Vibha; Roychoudhury, Pradip K

    2006-01-01

    An increased emphasis on prevention of fatalities due to thrombovascular disorders is broadening opportunities for several cardiovascular agents, especially plasminogen activators, for preventing strokes and heart attacks. Hence, urokinase, as one of the most potent plasminogen activators is attracting a great deal of attention. Developments in cell lines and bioprocess technology have made it possible to produce urokinase from in vitro cell culture. Attempts are now underway to enhance urokinase production from cell culture through media manipulation, bioreactor cultivation, and innovative purification techniques. Downstream processing also poses an intricate problem due to the complexity of cell culture extracts, susceptibility of urokinase to autocatalytic and proteolytic degradation and due to the presence of plasminogen activator inhibitors in the culture media. Hence, enhancing cellular productivity and downstream product recovery continue to be major challenges as discussed in this review. Furthermore, an approach for integrated upstream and downstream processing is needed to develop an economically viable technology. In the present review the emerging trends in urokinase production and purification have been discussed in detail.

  10. [Inadvertent epidural infusion of paracetamol].

    PubMed

    Charco Roca, L M; Ortiz Sánchez, V E; del Pino Moreno, A L

    2014-10-01

    A 45-year-old woman was accidentally administered an epidural infusion of paracetamol instead of levobupivacaine for postoperative pain therapy during the postoperative period of abdominal hysterectomy under general anesthesia combined with epidural analgesia. The patient had no neurological symptoms at any time, although a slight tendency to arterial hypotension that did not require treatment was observed. No rescue analgesia was necessary until 8h after the start of epidural infusion. The incidence of these types of errors is probably underestimated, although there are several cases reported with various drugs.

  11. 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. © The Author(s) 2016.

  12. Regulation of urokinase by cellular receptors and inhibitors

    SciTech Connect

    Hebert, C.A.

    1989-01-01

    Several cell types display binding sites for {sup 125}I-urokinase which in certain cases are occupied with endogenous urokinase. These sites appear to focus urokinase at cell surfaces and hence may participate in tissue matrix destruction and cell invasion. Using immunofluorescence double labeling, the author shows that the receptor-bound urokinase present on human foreskin fibroblasts and HT1080 human fibrosarcoma cells is colocalized with vinculin, an intracellular actin-binding protein that is deposited at cell to substratum focal adhesion sites. Thus, this indicates linkage of the plasminogen/plasmin system both to sites of cell adhesion and to the cytoskeleton. He furthermore reports that neither EGF, TGF{beta} or PDGF significantly altered the shape or intensity of the receptor-bound urokinase clusters but that thrombin, at mitogenic doses, caused a disappearance of the urokinase strands and a loss or gross alteration of the underlying focal adhesion plaques, as indicated by immunofluorescence staining for vinculin and talin, and by interference reflection microscopy. These observations suggest that thrombin may be a unique effector of cell adhesion, shape and movement. He used a quantitative in vitro invasion assay to study the role of plasminogen activator inhibitors type 1 and 2 (PAI-1, PAI-2) and protease nexin (PN1) in basement membrane (BM) invasion by {sup 125}I-iododeoxyuridine-labeled HT 1080 cells. The results obtained showed that 5 {mu}g/ml of PAI-1, PAI-2 and PN1 preadsorbed to the BM completely blocked HT1080 invasion. On the contrary an anti-PAI-1 monoclonal antibody induced an approximately two-fold increase in invasion. {sup 125}I-fibrinogen was polymerized on the amnion BM and the fibrinolytic activity of the cells was measured under the invasion assay conditions by measuring the radioactivity in the culture medium at different time points.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Reprogramming urokinase into an antibody-recruiting anticancer agent.

    PubMed

    Jakobsche, Charles E; McEnaney, Patrick J; Zhang, Andrew X; Spiegel, David A

    2012-02-17

    Synthetic compounds for controlling or creating human immunity have the potential to revolutionize disease treatment. Motivated by challenges in this arena, we report herein a strategy to target metastatic cancer cells for immune-mediated destruction by targeting the urokinase-type plasminogen activator receptor (uPAR). Urokinase-type plasminogen activator (uPA) and uPAR are overexpressed on the surfaces of a wide range of invasive cancer cells and are believed to contribute substantially to the migratory propensities of these cells. The key component of our approach is an antibody-recruiting molecule that targets the urokinase receptor (ARM-U). This bifunctional construct is formed by selectively, covalently attaching an antibody-binding small molecule to the active site of the urokinase enzyme. We demonstrate that ARM-U is capable of directing antibodies to the surfaces of target cancer cells and mediating both antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) against multiple human cancer cell lines. We believe that the reported strategy has the potential to inform novel treatment options for a variety of deadly, invasive cancers.

  18. 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

  19. [Continuous-infusion ketamine].

    PubMed

    Mancini, P G; Caggese, G; Di Fabio, A; Di Nino, G F; Cocchi, V

    1980-08-01

    An investigation was made of the employment of ketamin as the sole anaesthetic in general surgery, using continuous infusion of a 1% solution for both induction and maintenance in 118 cases. ECG was monitored and arterial pressure was measured invasively. Central venous pressure was also determined in 10 cases. Changes in serum enzyme values during and after surgery were examined in 35 patients. Blood samples were withdrawn before induction, after the return to consciousness, and 24 hr after the operation. Side-effects were common, but slight. Five patients suffered from nightmares, but these were persons with marked imaginative activity and a melancholic nature. Cardiocirculatory function was satisfactory. In particular, peripheral perfusion was excellent in all cases.

  20. Hepatic Arterial Infusion Chemotherapy through a Port-Catheter System as Preoperative Initial Therapy in Patients with Advanced Liver Dysfunction due to Synchronous and Unresectable Liver Metastases from Colorectal Cancer

    SciTech Connect

    Iguchi, Toshihiro; Arai, Yasuaki; Inaba, Yoshitaka Yamaura, Hidekazu; Sato, Yozo; Miyazaki, Masaya; Shimamoto, Hiroshi

    2008-01-15

    Purpose. We retrospectively evaluated the safety and efficacy of preoperative initial hepatic arterial infusion chemotherapy (HAIC) through a port-catheter system in patients with liver dysfunction due to synchronous and unresectable liver metastases. The aim of HAIC was to improve patients' clinical condition for later surgical removal of primary colorectal cancer. Methods. Port-catheter systems were placed radiologically in 21 patients (mean age 58.6 {+-} 8.1 years) with liver dysfunction due to synchronous liver metastases from colorectal cancer. Initial HAIC of 1,000 mg/m{sup 2} 5-fluorouracil was administered weekly as a 5 hr continuous infusion through this system. Surgical removal of the primary lesion was planned after HAIC improved the liver function. Results. Port-catheter system placement was successful in all patients without severe complications. Patients were followed up for a median of 309 days (range 51-998 days). After starting HAIC, no severe adverse events that caused drug loss and treatment postponement or suspension were observed in any of the patients. HAIC was performed a mean of 4.5 {+-} 3.0 times and the liver function improved in all patients. Curative (n = 18) or palliative (n = 1) surgical removal of the primary lesion was performed. The remaining 2 patients died because extrahepatic metastases developed and their performance status worsened; thus, surgery could not be performed. The median survival times of all patients and the operated patients were 309 and 386 days, respectively. Conclusion. Initial HAIC administration is a safe and efficacious method for improving liver function prior to operative resection of primary colorectal cancer in patients with liver dysfunction due to synchronous and unresectable liver metastases.

  1. Mature results of a pilot study of pelvic radiotherapy with concurrent continuous infusion intra-arterial 5-FU for stage IIIB-IVA squamous cell carcinoma of the cervix.

    PubMed

    Chaney, A W; Eifel, P J; Logsdon, M D; Morris, M; Wharton, J T

    1999-08-01

    To evaluate the long-term results of continuous infusion intra-arterial 5-fluorouracil (CI IA 5-FU) given with concurrent pelvic radiotherapy (RT) for FIGO stage IIIB-IVA carcinoma of the cervix. Between 1965 and 1974, 27 patients with extensive FIGO Stage IIIB (22 patients) or Stage IVA (5 patients) squamous cell carcinoma of the cervix were treated with CI IA 5-FU and RT. Twenty-one patients (78%) had bilateral pelvic wall involvement, 25 (93%) had massive tumors (> or =8 cm in diameter), 7 (27%) had involvement of the lower one-third of the vagina, and 15 (56%) presented with hydronephrosis. All patients underwent routine clinical staging, transperitoneal para-aortic lymph node dissection, and bilateral hypogastric artery catheter placement. 5-FU was continuously infused at a dose rate of 10 mg/kg/day on Days 1-15 of RT. The median dose of 5-FU was 376 mg/m2/day (range 270-692). All patients received concurrent pelvic RT to a median dose of 50 Gy at 2.0 Gy per fraction. Only 4 patients received intracavitary RT. The median follow-up of surviving patients was 190 months. The overall 5-year survival rate was 37%. For the 22 patients with FIGO Stage IIIB disease, the 5-year survival rate was 41%. The survival rate for 18 patients treated with only external beam radiation and chemotherapy for Stage IIIB disease was 33%. Four of 10 patients treated with only 50 Gy of external beam radiation and CI IA 5-FU were long-term survivors. Acute complications, including hematologic toxicity and skin reactions, were severe, with 1 death from neutropenic sepsis. Severe late complications were only observed in patients treated with > or =60 Gy of external beam radiation. While this series is small, the fact that 4 patients with massive Stage IIIB tumors survived after a total radiation dose of only 50 Gy suggests that RT with CI IA 5-FU deserves further study. Modifications in dose, technique, and route of administration should reduce toxicity, and the addition of intracavitary

  2. Effects and problems of adult ABO-incompatible living donor liver transplantation using protocol of plasma exchange, intra-arterial infusion therapy, and anti-CD20 monoclonal antibody without splenectomy: case reports of initial experiences and results in Korea.

    PubMed

    Kim, B-W; Park, Y-K; Kim, Y-B; Wang, H-J; Kim, M-W

    2008-12-01

    Adult ABO-incompatible liver transplantation is associated with a high risk of graft failure due to antibody-mediated humoral rejection (AMR). We evaluated the effects of a protocol using preoperative removal of isohemagglutinin, rituximab prophylaxis, and intrahepatic arterial infusion (HAI) therapy for ABO-incompatible adult living donor liver transplantation (LDLT). Between March 2005 and September 2007, we performed 94 adult LDLTs, including 3 ABO-incompatible cases. All ABO-incompatible LDLT patients underwent administration of 375 mg/m(2) rituximab on preoperative days 15 and 8 without splenectomy, as well as preoperative removal of isohemagglutinin using plasma exchange, and HAI therapy for postoperative 21 days. Postoperative anti-donor blood-type antibody titer and B-cell level were effectively suppressed by early rituximab prophylaxis in all patients. HAI therapy was effective to prevent AMR and even resolved mild AMR. However, all patients suffered bacterial infections, and 1 died of septicemia with good graft function. Another subject died of late-onset AMR that occurred after discontinuation of HAI therapy. An ABO-incompatible LDLT protocol using plasma exchange, rituximab prophylaxis, and intra-HAI therapy effectively suppressed anti-A/B antibody and prevented AMR. But this protocol should be further improved to reduce infectious complications and late onset of AMR.

  3. Cerebral oxygenation following epinephrine infusion.

    PubMed

    Steinback, Craig D; Zubin, Petra; Breskovic, Toni; Bakovic, Darija; Pivac, Nediljko; Dujic, Zeljko

    2012-10-15

    Evidence suggests that the autonomic nervous system may actively regulate the cerebral vasculature. In this study, central hemodynamics and brain oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin changes (bO₂Hb, bdHb and bTHb) were monitored during infusion of epinephrine (0.06 μg/kg/min over 6 min, and 0.12 μg/kg/min for 3 min) in 12 men. Epinephrine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and cardiac output (CO) increased, but did not affect bO₂Hb, bdHb or bTHb. However, upon the cessation of epinephrine infusion an increase in both Oxy- and Total Hb occurred which peaked at 3 min post infusion (+6.0±4.6 and +4.9±4.8 μmol/L respectively, P<0.05) and persisted for 20 min post infusion (+1.5±2.2 and +1.8±2.7 μmol/L respectively, P<0.05). No evidence was found for reduction in cerebral oxygenation during a cold-pressor test. The results of the present study demonstrated that clinical doses of epinephrine result in a delayed increase in cortical blood volume due to an increase in Oxy-Hb, consistent with vasodilation.

  4. Engraftment of Human Mesenchymal Stem Cells in a Rat Photothrombotic Cerebral Infarction Model : Comparison of Intra-Arterial and Intravenous Infusion Using MRI and Histological Analysis

    PubMed Central

    Byun, Jun Soo; Kim, Jae Kyun; Jung, Jisung; Ha, Bon Chul; Park, Serah

    2013-01-01

    Objective This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Methods Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2* weighted image (T2*WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Results Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2*WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. Conclusion In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain. PMID:24527188

  5. Urokinase has direct catalytic activity against fibrinogen and renders it less clottable by thrombin.

    PubMed Central

    Weitz, J I; Leslie, B

    1990-01-01

    Recently, we demonstrated that tissue plasminogen activator directly releases fibrinopeptides A and B (FPA and FPB) from fibrinogen. The purpose of this study was to determine whether urokinase has similar activity. Incubation of urokinase with fibrinogen or heparinized plasma results in concentration-dependent FPB release unaccompanied by FPA cleavage. For equivalent amidolytic activity, high molecular weight urokinase releases twofold more FPB than the low molecular weight species. In contrast, prourokinase does not release FPB until activated to urokinase. Contaminating thrombin or plasma is not responsible for urokinase-mediated FPB release because this activity is unaccompanied by FPA or B beta 1-42 cleavage, and is unaffected by heparin, hirudin, a monospecific antibody against thrombin, aprotinin, or alpha 2-antiplasmin. FPB release reflects a direct action of urokinase on fibrinogen because release is completely inhibited by a monospecific antibody against the enzyme. Further, urokinase releases FPB from the FPB-containing substrate B beta 1-42, thus confirming its specificity for the B beta 14 (Arg)-B beta 15 (Gly) bond. In addition to FPB release, SDS-PAGE analysis of the time course of urokinase-mediated fibrinogenolysis indicates progressive proteolysis of both the A alpha- and B beta-chains of fibrinogen that occurs after FPB release is completed. As a consequence of urokinase-mediated fibrinogenolysis, there is progressive prolongation of the thrombin clotting time. These studies indicate that urokinase has direct catalytic activity against fibrinogen. By releasing FPB, a potent chemoattractant, and by rendering fibrinogen less clottable by thrombin, urokinase may participate in processes extending beyond fibrinolysis. Images PMID:2365816

  6. Dissecting the Urokinase Activation Pathway Using Urokinase-Activated Anthrax Toxin

    PubMed Central

    Liu, Shihui; Bugge, Thomas H.; Frankel, Arthur E.; Leppla, Stephen H.

    2012-01-01

    Anthrax toxin is a three-part toxin secreted by Bacillus anthracis, consisting of protective antigen (PrAg), edema factor (EF), and lethal factor (LF). To intoxicate host mammalian cells, PrAg, the cell-binding moiety of the toxin, binds to cells and is then proteolytically activated by furin on the cell surface, resulting in the active heptameric form of PrAg. This heptamer serves as a protein-conducting channel that translocates EF and LF, the two enzymatic moieties of the toxin, into the cytosol of the cells where they exert cytotoxic effects. The anthrax toxin delivery system has been well characterized. The amino-terminal PrAg-binding domain of LF (residues 1–254, LFn) is sufficient to allow translocation of fused “passenger” polypeptides, such as the ADP-ribosylation domain of Pseudomonas exotoxin A, to the cytosol of the cells in a PrAg-dependent process. The protease specificity of the anthrax toxin delivery system can also be reengineered by replacing the furin cleavage target sequence of PrAg with other protease substrate sequences. PrAg-U2 is such a PrAg variant, one that is selectively activated by urokinase plasminogen activator (uPA). The uPA-dependent proteolytic activation of PrAg-U2 on the cell surface is readily detected by Western blotting analysis of cell lysates in vitro, or cell or animal death in vivo. Here we describe the use of PrAg-U2 as a molecular reporter tool to test the controversial question of what components are required for uPAR-mediated cell surface pro-uPA activation. The results demonstrate that both uPAR and plasminogen play critical roles in pro-uPA activation both in vitro and in vivo. PMID:19377974

  7. 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

  8. Human urokinase gene is located on the long arm of chromosome 10.

    PubMed Central

    Tripputi, P; Blasi, F; Verde, P; Cannizzaro, L A; Emanuel, B S; Croce, C M

    1985-01-01

    Urokinase is one of the two plasminogen activators that catalyze the conversion of inactive plasminogen to plasmin. By combining somatic cell genetics, in situ hybridization, and Southern hybridization, we localized the human urokinase gene on the distal third of the long arm (q24-qter) of chromosome 10. Images PMID:2989821

  9. 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.

  10. 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

  11. Hepatic arterial infusion chemotherapy using 5-fluorouracil and systemic interferon-α for advanced hepatocellular carcinoma in combination with or without three-dimensional conformal radiotherapy to venous tumor thrombosis in hepatic vein or inferior vena cava.

    PubMed

    Murakami, Eisuke; Aikata, Hiroshi; Miyaki, Daisuke; Nagaoki, Yuko; Katamura, Yoshio; Kawaoka, Tomokazu; Takaki, Shintaro; Hiramatsu, Akira; Waki, Koji; Takahashi, Shoichi; Kimura, Tomoki; Kenjo, Masahiro; Nagata, Yasushi; Ishikawa, Masaki; Kakizawa, Hideaki; Awai, Kazuo; Chayama, Kazuaki

    2012-05-01

      We investigated the efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) and systemic interferon (IFN)-α (HAIC-5-FU/IFN) for advanced hepatocellular carcinoma (HCC) with venous tumor thrombosis (VTT) in the hepatic vein trunk (Vv2) or inferior vena cava (Vv3).   Thirty-three patients with HCC/Vv2/3 underwent HAIC with 5-FU (500 mg/body weight/day, into hepatic artery on days 1-5 on the first and second weeks) and IFN-α (recombinant IFN-α-2b 3 000 000 U or natural IFN-α 5 000 000 U, intramuscularly on days 1, 3 and 5 of each week). Three-dimensional conformal radiotherapy (3D-CRT) was used in combination with HAIC-5-FU/IFN in 14 of 33 patients to reduce VTT.   The median survival time (MST) was 7.9 months, and 1- and 2-year survival rates were 30% and 20%, respectively. Evaluation of intrahepatic response after two cycles of HAIC-5-FU/IFN showed complete response (CR) in three (9%) and partial response (PR) in seven (21%), with an objective response rate of 30%. Multivariate analysis identified reduction of VTT (P = 0.0006), size of largest tumor (P = 0.013) and intrahepatic response CR/PR (P = 0.030) as determinants of survival. CR/PR correlated significantly with tumor liver occupying rate (P = 0.016) and hepatitis C virus Ab (P = 0.010). Reduction of VTT correlated significantly with radiotherapy (P = 0.021) and platelet count (P = 0.015). Radiotherapy-related reduction in VTT significantly improved survival of 16 patients with Vv3 and non-CR/PR response of HAIC-5-FU/IFN (P = 0.028).   As for advanced HCC with VTT of Vv2/3, HAIC-5-FU/IFN responsive patients could obtain favorable survival. Despite ineffective HAIC-5-FU/IFN, the combination with effective radiotherapy to VTT might improve patients' prognosis. © 2011 The Japan Society of Hepatology.

  12. Hepatic Arterial Infusion and Systemic Chemotherapy after Multiple Metastasectomy in Patients with Colorectal Carcinoma Metastatic to the Liver: A North Central Cancer Treatment Group (NCCTG) Phase II Study, 92-46-521

    PubMed Central

    Bolton, John S.; O’Connell, Michael J.; Mahoney, Michelle R.; Farr, Gist H.; Fitch, Tom R.; Maples, William J.; Nagorney, David M.; Rubin, Joseph; Fuloria, Jyotsna; Steen, Preston D.; Alberts, Steven R.

    2011-01-01

    BACKGROUND Patients with multiple liver metastases from colorectal cancer are at high risk of recurrence after resection. Hepatic artery infusion (HAI) alternating with systemic therapy after surgical resection may improve survival following surgery. METHODS Patients with liver-only metastases from colorectal cancer amenable to resection/cryoablation were eligible. Prior adjuvant chemotherapy for a completely resected primary was allowed. Alternating courses of HAI and systemic therapy included floxuridine (FUDR) via HAI. Systemic chemotherapy consisted of bolus leucovorin plus 5-fluorouracil (5-FU). RESULTS 49 patients were able to undergo complete resection of their liver metastases with 44% having more than 4 hepatic metastases and 78% having bilobar disease. 36 patients were able to initiate HAI FUDR alternating with systemic therapy. Patients received a median of 3.5 cycles (range 1–4) and 3 cycles (range 0–6) of therapy with HAI FUDR and systemic therapy, respectively. At the time of the final analysis the estimated median disease-free survival and hepatic disease-free survival are 1.2 years (95% CI: 0.9–2.1) and 1.8 years (95% CI: 1.8-NA), respectively. Eleven patients (31%) are alive. All surviving patients have a minimum of 5.5 years of follow-up CONCLUSIONS This trial of adjuvant chemotherapy in completely resected patients with unfavorable characteristics demonstrates apparent improvement in outcome compared to historical series treated with surgery alone. However, the results of this trial and other randomized trials of HAI do not appear to support its use at this time due to the development of more effective systemic options. PMID:21729678

  13. Alternating Systemic and Hepatic Artery Infusion Therapy for Resected Liver Metastases From Colorectal Cancer: A North Central Cancer Treatment Group (NCCTG)/ National Surgical Adjuvant Breast and Bowel Project (NSABP) Phase II Intergroup Trial, N9945/CI-66

    PubMed Central

    Alberts, Steven R.; Roh, Mark S.; Mahoney, Michelle R.; O'Connell, Michael J.; Nagorney, David M.; Wagman, Lawrence; Smyrk, Thomas C.; Weiland, Timothy L.; Lai, Lily Lau; Schwarz, Roderich E.; Molina, Roy; Dentchev, Todor; Bolton, John S.

    2010-01-01

    Purpose Prior trials have shown that surgery followed by hepatic artery infusion (HAI) of floxuridine (FUDR) alternating with systemic fluorouracil improves survival rates. Oxaliplatin combined with capecitabine has demonstrated activity in advanced colorectal cancer. Based on this observation a trial was conducted to assess the potential benefit of systemic oxaliplatin and capecitabine alternating with HAI of FUDR. The primary end point was 2-year survival. Patients and Methods Patients with liver-only metastases from colorectal cancer amenable to resection or cryoablation were eligible. HAI and systemic therapy was initiated after metastasectomy. Alternating courses of HAI consisted of 0.2 mg/m2/d FUDR and dexamethasone, day 1 through 14 weeks 1 and 2. Systemic therapy included oxaliplatin 130 mg/m2 day 1 with capecitabine at 1,000 mg/m2 twice daily, days 1 through 14, weeks 4 and 5. Two additional 3-week courses of systemic therapy were given. Capecitabine was reduced to 850 mg/m2 twice daily after interim review of toxicity. Results Fifty-five of 76 eligible patients were able to initiate protocol-directed therapy and completed median of six cycles (range, one to six). Three postoperative or treatment-related deaths were reported. Overall, 88% of evaluable patients were alive at 2 years. With a median follow-up of 4.8 years, a total of 30 patients have had disease recurrence, 11 involving the liver. Median disease-free survival was 32.7 months. Conclusion Alternating HAI of FUDR and systemic capecitabine and oxaliplatin met the prespecified end point of higher than 85% survival at 2 years and was clinically tolerable. However, the merits of this approach need to be established with a phase III trial. PMID:20048179

  14. Urokinase immobilized on medical polymeric materials: fundamental and clinical studies.

    PubMed

    Ohshiro, T; Kosaki, G

    1980-02-01

    One of the methods of preparing an antithrombogenic material is to immobilize a fibrinolytic enzyme on the surface of a carrier. The clinical trial of such a material must be subject to not only a basic study on the quality of a carrier, the technique of immobilization, and the method of disinfection, but also an in vivo study on its antithrombotic effect. Reported herein is the evaluation of the fibrinolytic ability, at fundamental and clinical levels, of the urokinase that was immobilized on the surface of various polymeric materials. The results were favorable.

  15. Urokinase treatment for arteriovenous fistulae declotting in dialyzed patients.

    PubMed

    Mangiarotti, G; Canavese, C; Thea, A; Segoloni, G P; Stratta, P; Salomone, M; Vercellone, A

    1984-01-01

    Urokinase treatment, previously employed with success in the declotting of deep venous thrombosis and arteriovenous shunts in patients undergoing regular dialytic treatment (RDT), was used in 23 cases of arteriovenous fistula thrombotic occlusion in 18 RDT patients. The treatment was successful in 65.2% of the cases without any negative side effects, except 1 case which may have developed a pulmonary embolism. Patients with severe hypofibrinolysis may need larger doses or may have a recurrence of the thrombotic episode. All therapeutic failures correlated with the presence of fibrosis or sclerosis.

  16. A new endovascular strategy utilizing a hybrid procedure for long segmental occlusion by acute arterial thromboembolism in the lower extremity.

    PubMed

    Kwak, JungWon; Chung, HwanHoon; Lee, SeungHwa; Kim, YunHwan; Cho, SungBum; Seo, TaeSuk; Jo, Wonmin; Shin, JaeSeung

    2016-07-01

    To evaluate a new endovascular strategy utilizing a hybrid procedure for long segmental arterial thromboembolism in a lower extremity by historical comparison with conventional endovascular strategy. In a new endovascular strategy, a hybrid procedure was performed for long segmental thromboembolism (longer than 15 cm) and an endovascular procedure for short segmental thromboembolism. The new strategy group (Group A) consisted of 24 procedures (13 hybrid procedures, 11 endovascular procedures) in 19 patients. Data were retrospectively collected from 24 consecutive procedures in 23 patients treated with the conventional strategy (Group B). The technical success of Groups A and B was 24/24 and 20/24, respectively (p = 0.11). Major amputation or mortality was not observed in Group A, whereas 3 major amputations and 4 deaths occurred in Group B. Clinical failure in Groups A and B was 0/24 and 7/24, respectively (p < 0.05). Continuous urokinase (UK) infusion was needed in 1/24 in Group A and 14/24 in Group B (p < 0.05). Mean procedure time was 4 h 17 min for Group A and 21 h 30 min for Group B (p < 0.05). The hybrid procedure may be faster and more effective than the conventional treatment in long segmental arterial thromboembolisms, while the conventional treatment is still effective for short segmental occlusions.

  17. Monocyte-expressed urokinase regulates human vascular smooth muscle cell migration in a coculture model.

    PubMed

    Kusch, Angelika; Tkachuk, Sergey; Lutter, Steffen; Haller, Hermann; Dietz, Rainer; Lipp, Martin; Dumler, Inna

    2002-01-01

    Interactions of vascular smooth muscle cells (VSMC) with monocytes recruited to the arterial wall at a site of injury, with resultant modulation of VSMC growth and migration, are central to the development of vascular intimal thickening. Urokinase-type plasminogen activator (uPA) expressed by monocytes is a potent chemotactic factor for VSMC and might serve for the acceleration of vascular remodeling. In this report, we demonstrate that coculture of human VSMC with freshly isolated peripheral blood-derived human monocytes results in significant VSMC migration that increases during the coculture period. Accordingly, VSMC adhesion was inhibited with similar kinetics. VSMC proliferation, however, was not affected and remained at the same basal level during the whole period of coculture. The increase of VSMC migration in coculture was equivalent to the uPA-induced migration of monocultured VSMC and was blocked by addition into coculture of soluble uPAR (suPAR). Analysis of uPA and uPAR expression in cocultured cells demonstrated that monocytes are a major source of uPA, whose expression increases in coculture five-fold, whereas VSMC display an increased expression of cell surface-associated uPAR. These findings indicate that upregulated uPA production by monocytes following vascular injury acts most likely as an endogenous activator of VSMC migration contributing to the remodeling of vessel walls.

  18. [Test for urokinase-type plasminogen activator inhibitor of edible plants in vitro].

    PubMed

    Fan, Yuan-Jing; Ohara, Akihiro; Matsuhisa, Tsugio

    2004-07-01

    To study the effect of anti-progression activity of edible plants using urokinase as the biomarker. Based on the assay of urokinase activity with peptide of Glu-Gly-Arg as the reaction substrate, extract of 25 fruits and 37 vegetables and water extract of tea were reacted against urokinase activity after Spectrozyme UK [carbobenzyl-1-gamma-Glu(alpha-t-BuO)-Gly-Arg-rho-nitroanilide. 2C2H5OH] was added and the residual urokinase activity was measured by the microplate photometer. About half of the fruit and vegetable samples showed urokinase inhibitory activity (UIA) at 20% or more and among them lemon, kiwi-fruit, peas, spinach and pumpkin showed effects over 80%, while garlic, radish, Japanese butterbur, garland chrysanthemum, celery, plum, pineapple and grape ranged between 50% and 79%. Average UIA of 51 kinds of tea was 83.2% and among them 28 kinds showed UIA over 90% and other 20 kinds of tea ranged from 70% to 89%. Green tea showed inhibitory effects on urokinase activity more powerful than black tea and Oolong tea. On the other hand, vegetable showed various UIA with different ways of processing. Comparing the effects of various solvents, garlic extracted with methanol, spinach with ethyl acetate, and pumpkin and radish with water showed highest UIA. Popular fruits, vegetables and tea in daily life could inhibit urokinase activity and may be helpful in the prevention of malignant tumor formation.

  19. Nuclear translocation of urokinase-type plasminogen activator

    PubMed Central

    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.

    2008-01-01

    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 α-actin (α-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. 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.

  1. Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer.

    PubMed

    Bouchahda, Mohamed; Boige, Valérie; Smith, Denis; Karaboué, Abdoulaye; Ducreux, Michel; Hebbar, Mohamed; Lepère, Céline; Focan, Christian; Guimbaud, Rosine; Innominato, Pasquale; Awad, Sameh; Carvalho, Carlos; Tumolo, Salvatore; Truant, Stephanie; De Baere, Thierry; Castaing, Denis; Rougier, Philippe; Morère, Jean-François; Taieb, Julien; Adam, René; Lévi, Francis

    2016-11-01

    Early tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m(2)) and triplet hepatic artery infusion (HAI) within European trial OPTILIV. Irinotecan (180 mg/m(2)), 5-fluorouracil (2800 mg/m(2)) and oxaliplatin (85 mg/m(2)) were given as chronomodulated or conventional delivery. Patients were retrospectively categorised as early responders (complete or partial RECIST response after three courses) or non-early responders (late or no response). Prognostic factors were determined using multivariate logistic or Cox regression models. Response was assessed in 57 of 64 registered patients (89%), who had previously received one to three prior systemic chemotherapy protocols. An early response occurred at 6 weeks in 16 patients (28%; 9 men, 7 women), aged 33-76 years, with a median of 12 liver metastases (LMs) (2-50), involving five segments (1-8). Ten patients had a late response, and 31 patients had no response. Grade 3-4 fatigue selectively occurred in the non-early responders (0% versus 26%; p = 0.024). Early tumour response was jointly predicted by chronomodulation-odds ratio (OR): 6.0 (1.2-29.8; p = 0.029)-and LM diameter ≤57 mm-OR: 5.3 (1.1-25.0; p = 0.033). Early tumour response predicted for both R0-R1 liver resection-OR: 11.8 (1.4-100.2; p = 0.024) and overall survival-hazard ratio: 0.39 (0.17-0.88; p = 0.023) in multivariate analyses. Early tumour response on triplet HAI and systemic cetuximab predicted for complete macroscopic liver resection and prolonged survival for LM-CRC patients within a multicenter conversion-to-resection medicosurgical strategy. Confirmation is warranted for early response on HAI to guide decision making. Protocol numbers: EUDRACT 2007-004632-24 NCT00852228. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 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

  3. 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

  4. Continuous transcatheter arterial thrombolysis for early hepatic artery thrombosis after liver transplantation.

    PubMed

    Zhou, J; Fan, J; Wang, J-H; Wu, Z-Q; Qiu, S-J; Shen, Y-H; Shi, Y-H; Huang, X-W; Wang, Z; Tang, Z-Y; Wang, Y-Q

    2005-12-01

    Early hepatic artery thrombosis (HAT) after orthotopic liver transplantation remains a significant cause of graft loss and patient death. The most effective treatment approach is still controversial. The purpose of this study was to assess the effect of continuous transcatheter arterial thrombolysis in the treatment of early HAT. Routine posttransplant color Doppler imaging (CDI) was performed to monitor hepatic artery blood flow. HAT was confirmed by arterial angiography in suspected cases. HAT was identified in 8 patients (8/287, 2.8%) which occurred on days 2 to 19 (mean, 5.2 days) after liver transplantation. Patients with HAT were treated with continuous transcatheter arterial thrombolysis using urokinase. Successful revascularization through thrombolysis was obtained in all eight cases. One patient died of a pulmonary infection at 2 months after liver transplantation. Another patient underwent retransplantation because of resistant allograft rejection and recurrence of HAT 6 months after the first operation, but died from multiple system organ failure 2 months later. The other six patients remained in good health during the follow-up period of 3 to 27 months. Our results demonstrate that CDI is an effective method to monitor the occurrence of early HAT after liver transplantation. Furthermore, continuous transcatheter arterial thrombolysis with urokinase could be a rational therapeutic approach to rescue the allograft following early HAT diagnosis confirmed by arterial angiography.

  5. 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.

  6. Urokinase type plasminogen activator receptor expression in colorectal neoplasms

    PubMed Central

    Suzuki, S; Hayashi, Y; Wang, Y; Nakamura, T; Morita, Y; Kawasaki, K; Ohta, K; Aoyama, N; Kim, S; Itoh, H; Kuroda, Y; Doe, W

    1998-01-01

    Background—The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis. 
Aims—To study the involvement of uPAR in colorectal carcinogenesis. 
Methods—The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses. 
Results—uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes' stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p<0.05); they were notably higher in Dukes' stage A than in severe dysplasia (p<0.05), and significantly higher in Dukes' stage B than in stage A (p<0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver. 
Conclusions—Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer. 

 Keywords: urokinase type plasminogen activator receptor; colorectal adenoma; colorectal cancer; adenoma-carcinoma sequence PMID:9824607

  7. Potent antitumor activity of a urokinase-activated engineered anthrax toxin

    NASA Astrophysics Data System (ADS)

    Liu, Shihui; Aaronson, Hannah; Mitola, David J.; Leppla, Stephen H.; Bugge, Thomas H.

    2003-01-01

    The acquisition of cell-surface urokinase plasminogen activator activity is a hallmark of malignancy. We generated an engineered anthrax toxin that is activated by cell-surface urokinase in vivo and displays limited toxicity to normal tissue but broad and potent tumoricidal activity. Native anthrax toxin protective antigen, when administered with a chimeric anthrax toxin lethal factor, Pseudomonas exotoxin fusion protein, was extremely toxic to mice, causing rapid and fatal organ damage. Replacing the furin activation sequence in anthrax toxin protective antigen with an artificial peptide sequence efficiently activated by urokinase greatly attenuated toxicity to mice. In addition, the mutation conferred cell-surface urokinase-dependent toxin activation in vivo, as determined by using a panel of plasminogen, plasminogen activator, plasminogen activator receptor, and plasminogen activator inhibitor-deficient mice. Surprisingly, toxin activation critically depended on both urokinase plasminogen activator receptor and plasminogen in vivo, showing that both proteins are essential cofactors for the generation of cell-surface urokinase. The engineered toxin displayed potent tumor cell cytotoxicity to a spectrum of transplanted tumors of diverse origin and could eradicate established solid tumors. This tumoricidal activity depended strictly on tumor cell-surface plasminogen activation. The data show that a simple change of protease activation specificity converts anthrax toxin from a highly lethal to a potent tumoricidal agent.

  8. Clinical applications of continuous infusion chemotherapy ahd concomitant radiation therapy

    SciTech Connect

    Rosenthal, C.J.; Rotman, M.

    1986-01-01

    This book presents information on the following topics: theoretical basis and clinical applications of 5-FU as a radiosensitizer; treatment of hepatic metastases from gastro intestingal primaries with split course radiation therapy; combined modality therapy with 5-FU, Mitomycin-C and radiation therapy for sqamous cell cancers; treatment of bladder carcinoma with concomitant infusion chemotherapy and irradiation; a treatment of invasiv bladder cancer by the XRT/5FU protocol; concomitant radiation therapy and doxorubicin by continuous infusion in advanced malignancies; cis platin by continuous infusion with concurrent radiation therapy in malignant tumors; combination of radiation with concomitant continuous adriamycin infusion in a patient with partially excised pleomorphic soft tissue sarcoma of the lower extremeity; treatment of recurrent carcinoma of the paranasal sinuses using concomitant infusion cis-platinum and radiation therapy; hepatic artery infusion for hepatic metastases in combination with hepatic resection and hepatic radiation; study of simultaneous radiation therapy, continuous infusion, 5FU and bolus mitomycin-C; cancer of the esophagus; continuous infusion VP-16, bolus cis-platinum and simultaneous radiation therapy as salvage therapy in small cell bronchogenic carcinoma; and concomitant radiation, mitomycin-C and 5-FU infusion in gastro intestinal cancer.

  9. Randomized comparison of intracoronary tirofiban versus urokinase as an adjunct to primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: results of the ICTUS-AMI trial.

    PubMed

    Zhu, Tian-qi; Zhang, Qi; Ding, Feng-hua; Qiu, Jian-ping; Jin, Hui-geng; Jiang, Li; Lu, Lin; Zhang, Rui-yan; Hu, Jian; Yang, Zhen-kun; Shen, Ying; Shen, Wei-feng

    2013-08-01

    No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI. A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%. In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P < 0.05). An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.

  10. Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets.

    PubMed

    Leifert, J A; Bossaller, L; Uhl, M

    2008-11-01

    Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms.

  11. Intracoronary ghrelin infusion decreases coronary blood flow in anesthetized pigs.

    PubMed

    Grossini, Elena; Molinari, Claudio; Mary, David A S G; Ghigo, Ezio; Bona, Gianni; Vacca, Giovanni

    2007-02-01

    The peptide ghrelin has been linked to the atherosclerotic process and coronary artery disease. We planned to study, for the first time, the primary effects of ghrelin on the intact coronary circulation and determine the mechanisms involved. In 24 sodium pentobarbitone-anesthetized pigs, changes in anterior descending coronary blood flow caused by intracoronary infusion of ghrelin at constant heart rate and arterial pressure were assessed using electromagnetic flowmeters. In 20 pigs, intracoronary infusion of ghrelin decreased coronary blood flow without affecting left ventricular maximum rate of change of left ventricular systolic pressure (dP/dt(max)), filling pressures of the heart or plasma levels of GH. In four pigs, this decrease was graded by step increments of infused dose of the hormone. The mechanisms of the above response were studied in the 20 pigs by repeating the experiment after coronary flow had returned to the control values observed before infusion. The ghrelin-induced coronary vasoconstriction was not affected by iv atropine (five pigs) or phentolamine (five pigs). This response was abolished by iv butoxamine (five pigs) and intracoronary N(omega)-nitro-l-arginine methyl ester (five pigs), even after reversing the increase in arterial pressure and coronary vascular resistance caused by the two blocking agents with iv infusion of papaverine. The present study showed that intracoronary infusion of ghrelin primarily caused coronary vasoconstriction. The mechanisms of this response were shown to involve the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect related to the release of nitric oxide.

  12. Interleukin-33 induces urokinase in human endothelial cells--possible impact on angiogenesis.

    PubMed

    Stojkovic, S; Kaun, C; Heinz, M; Krychtiuk, K A; Rauscher, S; Lemberger, C E; de Martin, R; Gröger, M; Petzelbauer, P; Huk, I; Huber, K; Wojta, J; Demyanets, S

    2014-06-01

    Urokinase-type plasminogen activator (u-PA) plays a pivotal role in extracellular proteolysis and is thought to be critically involved in the modulation of angiogenesis. Interleukin (IL)-33 is a member of the IL-1 cytokine family, which is thought to act as danger signal that is released from cells after injury. IL-33 is involved in the pathogenesis of various inflammatory diseases and previously was shown to induce angiogenesis and inflammatory activation of endothelial cells. We investigated the impact of IL-33 on u-PA in endothelial cells as a new possible function for IL-33. We could demonstrate that IL-33 upregulated u-PA mRNA expression and protein production in human coronary artery and human umbilical vein endothelial cells in a time- and concentration-dependent manner via interaction with its receptor ST2 and activation of the nuclear factor-κB pathway but independent of autocrine IL-1-induced effects. The hydroxymethylglutaryl-coenzyme A reductase inhibitor simvastatin abrogated the IL-33-induced increase in u-PA, thus providing further evidence for pleiotropic effects of statins. IL-33 induced u-PA-dependent capillary-like tube formation and vessel sprouting. In human carotid atherosclerotic plaques (n = 16), u-PA mRNA positively correlated with IL-33 mRNA expression (r = 0.780, P < 0.001). Furthermore, IL-33 and u-PA protein were detected in endothelial cells in these samples using fluorescence immunohistochemistry. We hypothesize that IL-33, representing a danger signal that is released after tissue damage, in addition to its role in the inflammatory activation of endothelial cells, is involved in u-PA-driven angiogenesis, a process that has been shown before to be linked to inflammation in various pathologies. © 2014 International Society on Thrombosis and Haemostasis.

  13. 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.

  14. 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.

  15. Randomised Controlled Trial of Urokinase versus Placebo for Non-draining Malignant Pleural Effusion.

    PubMed

    Mishra, Eleanor K; Clive, Amelia O; Wills, Genevieve H; Davies, Helen E; Stanton, Andrew E; Al-Aloul, Mohamed; Hart-Thomas, Alan; Pepperell, Justin; Evison, Matthew; Saba, Tarek; Harrison, Richard Neil; Guhan, Anur; Callister, Matthew E; Sathyamurthy, Ramamurthy; Rehal, Sunita; Corcoran, John P; Hallifax, Robert; Psallidas, Ioannis; Russell, Nicky; Shaw, Rachel; Dobson, Melissa; Wrightson, John M; West, Alex; Lee, Y C Gary; Nunn, Andrew J; Miller, Robert F; Maskell, Nick A; Rahman, Najib M

    2017-09-19

    Patients with malignant pleural effusion (MPE) experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with non-draining malignant effusion. Prospective double blind randomised trial; patients with non-draining effusion were randomly allocated 1:1 to intrapleural urokinase (100,000 IU three doses 12 hourly) or matched placebo. Co-primary outcome measures: dyspnea (average daily 100mm visual analogue scores over 28 days) and time to pleurodesis failure to 12 months. survival, time in hospital and radiographic change. 71 subjects randomised (36 received urokinase, 35 placebo) from 12 UK Centres. Baseline characteristics were similar between groups. There was no difference in mean dyspnea between groups (mean difference 3·8mm, 95% CI -12 to 4·4mm, p=0·36). Pleurodesis failure rates were similar (urokinase 13/35 (37%), placebo 11/34 (32%), adjusted hazard ratio 1·2, p=0·65). Urokinase was associated with a decreased effusion size on chest radiograph (adjusted relative improvement -19% (95% CI -28 to -11%, p<0·001), reduced hospital stay (1·6 days (95% CI 1·0 to 2·6), p=0·049) and improved survival (69 days versus 48 days, p=0.026). Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo, and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance and survival associated with urokinase require further evaluation. Clinical trial registration available at www.isrctn.com, ID 12852177.

  16. Current status of thrombolysis for peripheral arterial occlusive disease.

    PubMed

    Ouriel, Kenneth

    2002-11-01

    Acute peripheral arterial occlusion occurs as a result of thrombosis or embolism. A reduction in the prevalence of rheumatic heart disease accounts for a shift in the frequency of embolic to thrombotic occlusions. Also, a dramatic increase in the number of lower extremity arterial bypass graft procedures explains the predominance of graft occlusions in most recent series of patients with acute limb ischemia. While open surgical procedures remain the gold standard in the treatment of peripheral arterial occlusion, thrombolytic agents have been employed as an alternative to primary surgical revascularization in patients with acute limb ischemia. Systemic administration of thrombolytic agents, while effective for small coronary artery clots, fails to achieve dissolution of the large peripheral arterial thrombi. Catheter-directed administration of the agents directly into the occlusive thrombus is the only means of effecting early recanalization. Prior to 1999, urokinase was the sole agent used in North America for peripheral arterial indications, but the loss of the agent from the marketplace forced clinicians to turn to alternate agents, specifically alteplase and reteplase. Interest in the use of platelet glycoprotein inhibitors and mechanical thrombectomy devices also rose, coincident with the loss of urokinase from the marketplace. Most clinicians welcome the predicted return of urokinase to the marketplace. New investigative trials should be organized and executed to answer some of the remaining questions related to thrombolytic treatment of peripheral arterial disease. Foremost in this regard remains the question of which patients are best treated with percutaneous thrombolytic techniques and which are best treated with primary operative intervention. Ultimately, however, the thrombolytic agents are but one tool in the armamentarium of the vascular practitioner. This review is directed at providing the practicing clinician with the basic fund of knowledge

  17. Intraarterial infusion chemotherapy for head and neck cancer using a totally implantable infusion pump.

    PubMed

    Baker, S R; Wheeler, R H; Ensminger, W D; Niederhuber, J E

    1981-01-01

    Intraarterial infusion chemotherapy has not been widely accepted for the treatment of head and neck cancer due to the high rate of complications it involves. To avoid these complications, a totally implantable infusion pump has been developed to achieve continuous low-level drug delivery for long periods of time. The pump is implanted in a subcutaneous pocket and connected to a permanent, indwelling, arterial catheter. It can be repeatedly refilled with chemotherapeutic agents by hypodermic needle injection through the skin and through a self-sealing septum located at the entry to the pump. Refilling the pump recharges an inexhaustible power source for the next delivery cycle. Preliminary results suggest that long term intraarterial infusion chemotherapy for the treatment of head and neck cancer is practical for outpatients.

  18. 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.

  19. Understanding Infusion Pumps.

    PubMed

    Mandel, Jeff E

    2017-08-30

    Infusion systems are complicated electromechanical systems that are used to deliver anesthetic drugs with moderate precision. Four types of systems are described-gravity feed, in-line piston, peristaltic, and syringe. These systems are subject to a number of failure modes-occlusion, disconnection, siphoning, infiltration, and air bubbles. The relative advantages of the various systems and some of the monitoring capabilities are discussed. A brief example of the use of an infusion system during anesthetic induction is presented. With understanding of the functioning of these systems, users may develop greater comfort.

  20. Purification of c-phycocyanin from Spirulina fusiformis and its effect on the induction of urokinase-type plasminogen activator from calf pulmonary endothelial cells.

    PubMed

    Madhyastha, H K; Radha, K S; Sugiki, M; Omura, S; Maruyama, M

    2006-09-01

    c-Phycocyanin (c-pc), a blue coloured, fluorescent protein was purified from blue-green alga, Spirulina fusiformis and its effect on fibrinolytic system in vascular endothelial cells was investigated. The c-pc consisted of two subunits, alpha and beta, whose molecular masses were 16 and 17 kDa, respectively. N-terminal sequences of both subunits were well conserved compared with other blue green algal phycobiliproteins. Fibrinolytic activity in the medium conditioned by calf pulmonary arterial endothelial cells was measured by the fibrin plate method. The c-pc increased the fibrinolytic activity in dose- and time-dependent manners. Fibrin zymographic studies indicated that c-pc-induced urokinase-type plasminogen activator in the cells. These in vitro results suggest that c-pc from S. fusiformis is a potent profibrinolytic protein in the vascular endothelial system.

  1. Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography

    PubMed Central

    Panigada, Mauro; Zacchetti, Lucia; L’Acqua, Camilla; Cressoni, Massimo; Anzoletti, Massimo Boscolo; Bader, Rossella; Protti, Alessandro; Consonni, Dario; D’Angelo, Armando; Gattinoni, Luciano

    2015-01-01

    Introduction Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. Methods This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. Results UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6–13) vs 5 (4–7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93–0.98, p = 0.003). Conclusions Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality. PMID:26308340

  2. Urokinase, a promising candidate for fibrinolytic therapy for intracerebral hemorrhage.

    PubMed

    Tan, Qiang; Chen, Qianwei; Niu, Yin; Feng, Zhou; Li, Lin; Tao, Yihao; Tang, Jun; Yang, Liming; Guo, Jing; Feng, Hua; Zhu, Gang; Chen, Zhi

    2017-02-01

    OBJECTIVE Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study. METHODS Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor-κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH. RESULTS In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH. CONCLUSIONS This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

  3. Urokinase induces activation of STAT3 in lung epithelial cells.

    PubMed

    Shetty, Sreerama; Rao, Gadiparthi N; Cines, Douglas B; Bdeir, Khalil

    2006-10-01

    Urokinase-type plasminogen activator (uPA) is a serine protease that plays a major role in diverse physiological and pathological processes. Studies from our laboratory have shown that exposure of human lung epithelial cells to uPA induces proliferation. To understand uPA mitogenic signaling events, we sought to elucidate its effects on tyrosine phosphorylation in a human bronchial epithelial cell line (Beas2B). uPA induced tyrosine phosphorylation of several proteins in a time-dependent manner. One of these proteins was identified as the 91-kDa signal transduction activator transcription (Stat)3 moiety. Tyrosine phosphorylation of Stat3 by uPA was time dependent. uPA induced Stat3-DNA binding activity in a time-dependent manner. uPA-induced Stat3 activation does not require uPA catalytic activity, as the uPA amino-terminal fragment alone was as potent as active two-chain uPA (tcuPA) in causing this effect. Single-chain uPA likewise induced tyrosine phosphorylation of Stat3 to a similar extent as intact tcuPA. Plasmin did not alter uPA-induced Stat3 activation. Furthermore, transfection of Beas2B cells with dominant-negative Stat3 blocked uPA-induced DNA synthesis. These results reveal for the first time that the uPA-uPAR interaction leads to activation of Stat3, independent of its catalytic activity but dependent on its interaction with its receptor, uPAR, leading to DNA synthesis in lung epithelial cells.

  4. The Urokinase/Urokinase Receptor System in Mast Cells: Effects of its Functional Interaction with fMLF Receptors

    PubMed Central

    Rossi, Francesca Wanda; Prevete, Nella; Rivellese, Felice; Napolitano, Filomena; Montuori, Nunzia; Postiglione, Loredana; Selleri, Carmine; de Paulis, Amato

    2016-01-01

    Mast cell and basophils express the high affinity receptor for IgE (FcɛRI) and are primary effector cells of allergic disorders. The urokinase (uPA)-mediated plasminogen activation system is involved in physiological and pathological events based on cell migration and tissue remodelling, such as inflammation, wound healing, angiogenesis and metastasis. uPA is a serine protease that binds uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)-anchored receptor. uPAR focuses uPA activity at the cell surface and activates intracellular signaling through lateral interactions with integrins, receptor tyrosine kinases and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs). We investigated the expression of the uPA-uPAR system and its functional interaction with FPRs in human mast cells (MCs). Differently from basophils, MCs produced uPA that was able to induce their chemotaxis. Indeed, MCs also expressed uPAR, both in the intact and in a cleaved form (DII-DIII-uPAR) that can expose, at the N-terminus, the SRSRY sequence, able to interact with FPRs and to mediate cell chemotaxis. MCs also expressed mRNAs for FPRs that were functionally active; indeed, uPA and a soluble peptide (uPAR84–95), containing the SRSRY chemotactic sequence of uPAR and able to interact with FPRs, were able to induce MCs chemotaxis. Thus, uPA is a potent chemoattractant for MCs acting through the exposure of the chemotactic epitope of uPAR, that is an endogenous ligand for FPRs. The same mechanism could be involved in VEGF-A secretion by human MCs, also induced by uPA and uPAR84–95 stimulation. PMID:27896225

  5. Green Propellant Infusion Mission

    NASA Image and Video Library

    2013-07-09

    Roger Myers, Executive Director, Aerojet Rocketdyne speaks at a Green Propellant Infusion Mission press conference at the Reserve Officers Association, Tuesday, July 9, 2013 in Washington. The NASA GPIM program, led by Ball Aerospace in conjunction with Aerojet Rocketdyne, is demonstrating a high-performance "green" fuel in space. The propellant used on this mission offers nearly 50 percent better performance when compared to traditional hydrazine. Photo Credit: (NASA/Carla Cioffi)

  6. Green Propellant Infusion Mission

    NASA Image and Video Library

    2013-07-09

    Dr. Michael Gazarik, Associate Administrator, NASA Space Technology Mission Directorate, answers a reporter's question at a Green Propellant Infusion Mission press conference at the Reserve Officers Association, Tuesday, July 9, 2013 in Washington. The NASA GPIM program, led by Ball Aerospace in conjunction with Aerojet Rocketdyne, is demonstrating a high-performance "green" fuel in space. The propellant used on this mission offers nearly 50 percent better performance when compared to traditional hydrazine. Photo Credit: (NASA/Carla Cioffi)

  7. Green Propellant Infusion Mission

    NASA Image and Video Library

    2013-07-09

    U.S. Senator Mark Udall (D-CO) speaks at a Green Propellant Infusion Mission press conference at the Reserve Officers Association, Tuesday, July 9, 2013 in Washington. The NASA GPIM program, led by Ball Aerospace in conjunction with Aerojet Rocketdyne, is demonstrating a high-performance "green" fuel in space. The propellant used on this mission offers nearly 50 percent better performance when compared to traditional hydrazine. Photo Credit: (NASA/Carla Cioffi)

  8. Urokinase receptor modulates cellular and angiogenic responses in obstructive nephropathy.

    PubMed

    Zhang, Guoqiang; Kim, Heungsoo; Cai, Xiaohe; Lopez-Guisa, Jesus M; Carmeliet, Peter; Eddy, Allison A

    2003-05-01

    Interstitial cells have been implicated in the pathogenesis of renal fibrosis. Given that the urokinase receptor (uPAR) is known to play a role in cell adhesion, migration, and angiogenesis, the present study was designed to evaluate the role of uPAR in the regulation of the phenotypic composition of interstitial cells (macrophages, myofibroblasts, capillaries) in response to chronic renal injury. Groups of uPAR wild-type (+/+) and knockout (-/-) mice were investigated between 3 and 14 d after unilateral ureteral obstruction (UUO) or sham surgery (n = 8 mice per group). The density of F4/80+ interstitial macrophages (Mphi) was significantly lower in the -/- mice (3.3 +/- 0.4 versus 6.9 +/- 1.7% area at day 3 UUO; 10.8 +/- 1.6 versus 15.7 +/- 1.0% at day 14 UUO; -/- versus +/+). In contrast, in the -/- mice there were significantly more alpha smooth muscle actin (alphaSMA)-positive cells (12.9 +/- 3.2 versus 7.8 +/- 1.5% area at day 3 UUO; 21.0 +/- 4.7 versus 9.7 +/- 1.9% at day 14 UUO) and CD34-positive endothelial cells (8.4 +/- 1.9 versus 4.0 +/- 1.1% area at day 14 UUO). These differences were associated with significantly more interstitial fibrosis in the -/- mice based on Sirius red staining (4.6 +/- 0.9 versus 2.3 +/- 0.9% area at 14 d UUO). Absence of the uPAR scavenger receptor was associated with significantly greater accumulation of plasminogen activator inhibitor-1 protein (PAI-1) (20.5 +/- 3.5 versus 9.1 +/- 2.9% area, day 14 UUO) and vitronectin protein (2.4 +/- 1.1 versus 0.9 +/- 0.4% area, day 14 UUO). By immunostaining alphaSMA+ cells, CD34+ cells, vitronectin and PAI-1 co-localized to the same tubulointerstitial area. The number of apoptotic cells increased in response to UUO but was significantly higher in the -/- mice (2.0 +/- 0.2 versus 1.2 +/- 0.2 per 100 tubulointerstitial cells, day 14 UUO) while the number of proliferating cells was significantly lower in the uPAR-/- mice. These data suggest that uPAR deficiency suppresses renal Mphi

  9. Dissecting aneurysm of the middle cerebral artery treated with heparin infusion in a 6-year-old child; neurological recovery with delayed spontaneous thrombosis: case illustration and literature review.

    PubMed

    Anichini, G; Passacantilli, E; Lenzi, J; Guidetti, G; Santoro, A

    2012-04-01

    Aneurysms in the pediatric population are a rare pathology with specific features which requires a deep knowledge of their pathogenesis for the best therapeutic choice; the authors report their experience with a patient presenting aneurysm of the middle cerebral artery (MCA) associated with proximal stenosis of the vessel. A six-year-old girl came to our observation after sudden onset of headache and left hemiparesis. Angio-MRI and angio-CT scan showed a right MCA dissecting aneurysms associated with proximal stenosis of the vessel. Patient started a therapy with low molecular weight heparin (LMWH), replaced, 15 days later, with acetyl-salicylic acid (ASA). Patient showed a rapid and almost complete neurological recovery, despite several radiological exams confirmed a complete occlusion of the right MCA. As many other authors noted, dissecting aneurysms in the pediatric population are probably due to a defect of the entire arterial wall. Combination of stenosis, turbulence and partial thrombosis of the aneurysm led to a complete occlusion of artery involved, leading to the formation of collateral circles. In our case, complete thrombosis was probably delayed with anticoagulant therapy and the progressive reinforcement of collateral circles lead to the patient's neurological recovery.

  10. Stimulation of renin release by intrarenal calcium infusion.

    PubMed

    Lahera, V; Fiksen-Olsen, M J; Romero, J C

    1990-02-01

    The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca/kg/min) on renin secretion were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 minutes each (1 ml/min). In a second group, the same doses were administered 30 minutes after the start of infusion of prostaglandin synthesis inhibitors (indomethacin 10 micrograms/kg/min intrarenal or injection of meclofenamate 5 mg/kg i.v. bolus). Mean arterial pressure, renal blood flow, and glomerular filtration rate remained unchanged during the infusion of calcium in both groups. The infusion of 10 micrograms Ca/kg/min increased renin secretion 77% and sodium excretion 123%. During the infusion of 100 micrograms Ca/kg/min, renin secretion was not different from precalcium values, whereas urinary 6-keto-PGF1 alpha, urine flow, sodium, potassium, and calcium excretion rates were increased (p less than 0.05). During the administration of prostaglandin synthesis inhibitors, the urinary 6-keto-PGF1 alpha levels were reduced, and the infusion of 10 micrograms Ca/kg/min failed to increase renin secretion, sodium excretion, or 6-keto-PGF1 alpha excretion rates. The infusion of 100 micrograms Ca/kg/min during prostaglandin synthesis inhibition did not modify urine flow or sodium excretion; however, potassium and calcium excretions increased. It is concluded that 1) the intrarenal infusion of small doses of calcium gluconate is capable of stimulating renin secretion through a prostaglandin-mediated mechanism, and 2) the stimulation of renin secretion as well as the increase in sodium excretion induced by calcium are independent of hemodynamic alterations.

  11. 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.

  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. 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. A simple method to ensure homogeneous drug distribution during intrarenal infusion.

    PubMed

    Postnov, Dmitry D; Salomonsson, Max; Sorensen, Charlotte M; Sosnovtseva, Olga

    2017-03-01

    Intrarenal drug infusion plays an important role in renal experimental research. Laminar flow of the blood can cause streaming and inhomogeneous intrarenal distribution of infused drugs. We suggest a simple method to achieve a homogeneous intravascular distribution of drugs infused into the renal artery of anesthetized rats. The method employs a multiple sidehole catheter inserted into the renal artery, which enables an efficient drug mixing with the arterial blood. To verify the efficiency of this method, we use laser speckle imaging and renal artery flowmetry. The results show that, compared with the conventional single-hole catheter, the multiple sidehole catheter provides a more uniform drug distribution and a homogenous vascular response on the surface of the kidney. Copyright © 2017 the American Physiological Society.

  15. Changes in Basal Insulin Infusion Rates With Subcutaneous Insulin Infusion

    PubMed Central

    Heinemann, Lutz; Nosek, Leszek; Kapitza, Christoph; Schweitzer, Matthias-Axel; Krinelke, Lars

    2009-01-01

    OBJECTIVE Evaluation of the time required until a change in the basal insulin infusion rate with an insulin pump induces subsequent changes in the metabolic effect. RESEARCH DESIGN AND METHODS In this euglycemic glucose clamp study, 10 male subjects with type 1 diabetes received three different subcutaneous insulin infusion rates (0.5, 1.0, and 2.0 units/h; for 4 h each) of insulin lispro (IL) with insulin pumps. RESULTS An increase in insulinemia occurred within 15–30 min after changing the infusion rate. While the serum IL levels reached a steady state at the end of the infusion period, the glucose infusion rates did not always reach steady-state levels with the higher infusion rates. However, an increase in the glucose consumption occurred within 30–60 min after switching the infusion rate. CONCLUSIONS Several hours are required until a new steady state in the metabolic effect is achieved after a significant change in basal insulin infusion. PMID:19487635

  16. Urokinase receptor (uPAR) ligand based recombinant toxins for human cancer therapy.

    PubMed

    de Virgilio, Maddalena; Silvestris, Franco

    2011-01-01

    The urokinase receptor (uPAR) exerts essential functions in the pathophysiology of cancers and therefore constitutes an important drug target. In order to generate efficient drugs against uPAR, a new approach includes chimeric proteins associating one molecular address to specifically target uPAR and one bacterial or plant toxin that will eventually kill the tumoural cell. Using this frame, several recombinant toxins have been designed namely DTAT, DTAT13, EGFATFKDEL 7 mut, and ATF-SAP. As molecular address, all of these fusion proteins use the amino-terminal fragment of urokinase that binds with high affinity to uPAR through its growth factor domain (GFD). The various toxin moieties were derived from either diphtheria toxin, Pseudomonas exotoxin A (PE38), or saporin. In this review, we describe the rational, design, production and therapeutic anti-cancer potential of these chimeric toxins.

  17. A case of acute myocardial infarction during 5-fluorouracil infusion.

    PubMed

    Canale, Maria Laura; Camerini, Andrea; Stroppa, Stefano; Porta, Romana Prosperi; Caravelli, Paolo; Mariani, Mario; Balbarini, Alberto; Ricci, Sergio

    2006-11-01

    Cardiac toxicity is an uncommon side-effect of 5-fluorouracil (5-FU) treatment, consisting mainly of chest pain episodes with or without electrocardiographic changes and dysrhythmias. Here, we describe the case of a 56-year-old male patient with a diagnosis of advanced colorectal cancer who developed an acute myocardial infarction during 5-FU infusion. The patient was not affected by prior heart disease and did not show any classic risk factors for coronary heart disease. Coronary angiography examination revealed no evidence of coronary stenosis, supporting the hypothesis of a coronary artery spasm related to 5-FU infusion. Given the great number of cancer patients receiving 5-FU containing chemotherapeutic regimens, this rare but severe cardiac side-effect may be observed in both cardiologic and oncologic clinical practice. We suggest a tight clinical monitoring of all patients receiving 5-FU infusions, even in those without a prior history of heart disease.

  18. Coronary Arteries

    MedlinePlus

    ... and animations for grades K-6. The Coronary Arteries Coronary Circulation The heart muscle, like every other ... into two main coronary blood vessels (also called arteries). These coronary arteries branch off into smaller arteries, ...

  19. 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.

  20. A cleavage-resistant urokinase plasminogen activator receptor exhibits dysregulated cell-surface clearance.

    PubMed

    Nieves, Evelyn C; Manchanda, Naveen

    2010-04-23

    Urokinase plasminogen activator receptor (u-PAR) binds urokinase plasminogen activator (u-PA) and participates in plasminogen activation in addition to modulating several cellular processes such as adhesion, proliferation, and migration. u-PAR is susceptible to proteolysis by its cognate ligand and several other proteases. To elucidate the biological significance of receptor cleavage by u-PA, we engineered and expressed a two-chain urokinase plasminogen activator (tcu-PA) cleavage-resistant u-PAR (cr-u-PAR). This mutated receptor was similar to wild-type u-PAR in binding u-PA and initiating plasminogen activation. However, cr-u-PAR exhibited accelerated internalization and resurfacing due to direct association with the endocytic receptor alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein in the absence of the enzyme x inhibitor complex of tcu-PA and plasminogen activator inhibitor-1 (tcu-PA.PAI-1). cr-u-PAR-expressing cells had enhanced migration compared with wild-type u-PAR-expressing cells, and cr-u-PAR was less sensitive to chymotrypsin cleavage as compared with wt u-PAR. Our studies suggest that these mutations in the linker region result in a rearrangement within the cr-u-PAR structure that makes it resemble its ligand-bound form. This constitutively active variant may mimic highly glycosylated cleavage-resistant u-PAR expressed in certain highly malignant cancer-cells.

  1. Prophylaxis with urokinase in pediatric oncology patients with central venous catheters.

    PubMed

    Kalmanti, Maria; Germanakis, John; Stiakaki, Eftichia; Syfridaki, Cathrin; Christidou, Athanasia; Tsetis, Dimitris; Vardas, Panagiotis; Charisis, George

    2002-01-01

    This study evaluated the effects of urokinase in the prevention of central venous catheter (CVC)-related complications in children with malignancy. Fifteen patients with 16 CVCs (study group A) received an intraluminal application of urokinase (10,000 IU in each catheter lumen for 4 h) once a week. They were monitored prospectively with quantitative blood cultures and ultrasonography (color Doppler ultrasound of the great veins and echocardiography). The rate of complications was compared with that of 15 children with 19 CVCs without thromboprophylaxis, treated the previous significantly lower incidence of CVC dysfunction year (control group B). The authors found a wer incidence of CVC dysfunction (3/16 versus 13/19), no major thrombosis, fewer CVC-related bacteremias (2/16 versus 8/19), and a higher salvage of CVCs (1/16 versus 5/19 CVC removals due to persistent bacteremia) in the thromboprophylaxis group. Asymptomatic thrombosis rate was also lower (7/16 cases in group A versus 9/11 in group B when sonography was performed). No hemorrhagic complications were noted. Thromboprophylaxis with urokinase seems a safe and effective measure for reducing the rate of CVC-related complications.

  2. Urokinase Separation from Cell Culture Broth of a Human Kidney Cell Line

    PubMed Central

    Bansal, Vibha; Roychoudhury, Pradip K.; Kumar, Ashok

    2007-01-01

    A single step ion-exchange chromatography on a sulfo-propyl (SP)- Sepharose column was performed to separate both the high molecular weight (HMW)- and low molecular weight (LMW)- forms of enzymatically active urokinase type plasminogen activator from human kidney (HT1080) cell culture media. The level of urokinase secreted by the cell line reached to about 145 Plough units/ml culture broth within 48 h of cultivation. The conditioned cell culture media was applied directly to the column without any prior concentration steps. Polyacrylamide gel electrophoresis of the column eluates in the presence of sodium dodecyl sulphate showed that the cell line secretes three forms of two-chain high molecular weight (HMW) urokinase of molecular weights (Mr) 64,000, 60,900 and 55,000. In addition, two low molecular weight (LMW) forms of Mr 22,000 and 20,000; proteolytic cleavage products of HMW, were also found. The HMW and LMW forms had intrinsic plasminogen dependent proteolytic activity as judged by zymographic analysis. The specific activity of the pooled peak fractions increased (approximately 93-fold) to values as high as 1481 Plough units/ mg protein. Both HMW as well as LMW forms were obtained in significantly high yields. PMID:17200693

  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. Sites of pulmonary vasomotor reactivity in the dog during alveolar hypoxia and serotonin and histamine infusion

    PubMed Central

    Glazier, Jon B.; Murray, John F.

    1971-01-01

    In order to evaluate separately changes in vascular tone occurring in arteries and veins, we measured pulmonary capillary red blood cell (RBC) concentration under zone II (waterfall) conditions in isolated dog lungs rapidly frozen with Freon 12. The lungs were frozen while being perfused from artery to vein and from vein to artery breathing normal and hypoxic gas mixtures and during infusions of serotonin and histamine. Changes in capillary RBC concentration which occurred during the experimental conditions indicated an alteration in vascular resistance upstream from the capillaries. Alveolar hypoxia caused a significant decrease in capillary RBC concentration during forward perfusion, but no change from the control values during reverse perfusion. Serotonin infusion caused a decrease in RBC concentration during forward perfusion comparable with that of hypoxia and a small but significant decrease during reverse perfusion. Histamine infusion caused no change in RBC concentration from control values during forward perfusion, but a large decrease during reverse perfusion. We conclude that vasoconstriction occurs (a) exclusively in arteries during alveolar hypoxia, (b) predominantly in arteries but to a lesser extent in veins during serotonin infusion, and (c) exclusively in veins during histamine infusion. PMID:5129307

  5. 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.

  6. Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer

    SciTech Connect

    Kinsella, T.J.; Mitchell, J.B.; Russo, A.; Aiken, M.; Morstyn, G.; Hsu, S.M.; Rowland, J.; Glatstein, E.

    1984-10-01

    Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 x 10(-7) mol/L and 1 x 10(-6) mol/L during infusion of 650 and 1000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). The authors conclude that local and systemic toxicity of continuous infusion of BUdR at 1000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.

  7. [Intraduodenal infusion of levodopa].

    PubMed

    Valldeoriola, Francesc; Cámara, Ana

    2010-07-01

    In the advanced stages of Parkinson's disease (PD), the conventional orally-administered pharmacological treatment can prove to be insufficient to control the motor complications associated with the disease. One of the causes involved in the genesis of the motor fluctuations that are observed in PD is the variable absorption of the medication due to an irregular or erratic emptying of the gastric content. Today, a method of therapy is now available that allows levodopa to be administered directly into the duodenum at a continuous rate by a perfusor. The medication is applied through a duodenal catheter implanted by means of a percutaneous endoscopic gastrostomy. This new form of administration has been marketed under the name of Duodopa, which is a pharmaceutical form of levodopa in a micronised suspension in a thickening gel consisting of sodium carmelose. It is presented in combination with levodopa (20 mg/mL) and a dopa decarboxylase inhibitor, carbidopa (5 mg/mL). Duodopa has proved to be effective in reducing the percentage of off time and in diminishing the periods with disabling dyskinesias. This therapy has also proved to be useful for relieving certain non-motor aspects associated with PD and presents fewer limitations regarding indication for advanced PD patients than those that usually exist for the case of deep brain stimulation. Although the therapy has proved to be effective, it is not free of complications arising from malfunctioning of the infusion system or in relation to the percutaneous endoscopic gastrostomy.

  8. Intrapleural Fibrinolysis with Urokinase Versus Alteplase in Complicated Parapneumonic Pleural Effusions and Empyemas: A Prospective Randomized Study.

    PubMed

    Alemán, Carmen; Porcel, José M; Alegre, José; Ruiz, Eva; Bielsa, Silvia; Andreu, Jordi; Deu, Maria; Suñé, Pilar; Martínez-Sogués, Mireia; López, Iker; Pallisa, Esther; Schoenenberger, Joan Antoni; Bruno Montoro, J; de Sevilla, Tomás Fernández

    2015-12-01

    Pleurofibrinolysis has been reported to be potentially beneficial in the management of complicated parapneumonic effusions (CPPE) and empyemas in the adult population. Prospective, controlled, randomized, and double-blind study, to evaluate intrapleural alteplase 10 mg (initially 20 mg was considered but bleeding events forced dose reduction) versus 100,000 UI urokinase every 24 h for a maximum of 6 days in patients with CPPE or empyemas. The primary aim was to evaluate the success rate of each fibrinolytic agent at 3 and 6 days. Success of therapy was defined as the presence of both clinical and radiological improvement, making additional fibrinolytic doses unnecessary, and eventually leading to resolution. Secondary outcomes included the safety profile of intrapleural fibrinolytics, referral for surgery, length of hospital stay, and mortality. A total of 99 patients were included, of whom 51 received alteplase and 48 urokinase. Success rates for urokinase and alteplase at 3 and 6 days were not significantly different, but when only the subgroup of CPPE was considered, urokinase resulted in a high proportion of cures. There were no differences in mortality or surgical need (overall, 3 %). Five (28 %) patients receiving 20 mg of alteplase and 4 (12 %) receiving 10 mg presented serious bleeding events. If intrapleural fibrinolytics are intended to be used, urokinase may be more effective than alteplase in patients with non-purulent CPPE and have a lower rate of adverse events.

  9. Taking aim at infusion confusion.

    PubMed

    Burdeu, Gabrielle; Crawford, Ruth; van de Vreede, Melita; McCann, Joanne

    2006-01-01

    A comprehensive multidisciplinary approach was used to improve drug infusion safety in an acute care hospital in Melbourne, Australia. This project aimed to reduce the potential for drug infusion-related error, improve drug infusion safety for patients, and encourage incident reporting to inform and guide continuous quality improvement projects. The project applied a systems approach to medication safety, using redesign strategies such as continuous quality improvement (plan, do, study, and act) and re-engineering. Key safety design concepts such as standardization, simplification, and forcing functions were also used.

  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.

  11. 3D-FIESTA Magnetic Resonance Angiography Fusion Imaging of Distal Segment of Occluded Middle Cerebral Artery.

    PubMed

    Kuribara, Tomoyoshi; Haraguchi, Koichi; Ogane, Kazumi; Matsuura, Nobuki; Ito, Takeo

    2015-01-01

    Middle cerebral artery (MCA) occlusion was examined with basi-parallel anatomical scanning (BPAS) using three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA), and 3D-FIESTA and magnetic resonance angiography (MRA) fusion images were created. We expected that an incidence of hemorrhagic complications due to vessel perforations would be decreased by obtaining vascular information beyond the occlusion and thus acute endovascular revascularization could be performed using such techniques. We performed revascularization for acute MCA occlusion for five patients who were admitted in our hospital from October 2012 to October 2014. Patients consisted of 1 man and 4 women with a mean age of 76.2 years (range: 59-86 years). Fusion images were created from three-dimensional time of flight (3D-TOF) MRA and 3D-FIESTA with phase cycling (3D-FIESTA-C). Then thrombectomy was performed in all the 5 patients. Merci retriever to 1 patient, Penumbra system to 1, urokinase infusion to 2, and Solitaire to 1 using such techniques. In all cases, a 3D-FIESTA-MRA fusion imaging could depict approximately clear vascular information to at least the M3 segment beyond the occlusion. And each acute revascularization was able to perform smoothly using these imaging techniques. In all cases, there was no symptomatic hemorrhagic complication. It showed that 3D-FIESTA MRA fusion imaging technique could obtain vascular information beyond the MCA occlusion. In this study, no symptomatic hemorrhagic complications were detected. It could imply that such techniques were useful not only to improve treatment efficiency but also to reduce the risk of development of hemorrhagic complications caused by vessel perforations in acute revascularization.

  12. 3D-FIESTA Magnetic Resonance Angiography Fusion Imaging of Distal Segment of Occluded Middle Cerebral Artery

    PubMed Central

    KURIBARA, Tomoyoshi; HARAGUCHI, Koichi; OGANE, Kazumi; MATSUURA, Nobuki; ITO, Takeo

    2015-01-01

    Middle cerebral artery (MCA) occlusion was examined with basi-parallel anatomical scanning (BPAS) using three-dimensional fast imaging employing steady-state acquisition (3D-FIESTA), and 3D-FIESTA and magnetic resonance angiography (MRA) fusion images were created. We expected that an incidence of hemorrhagic complications due to vessel perforations would be decreased by obtaining vascular information beyond the occlusion and thus acute endovascular revascularization could be performed using such techniques. We performed revascularization for acute MCA occlusion for five patients who were admitted in our hospital from October 2012 to October 2014. Patients consisted of 1 man and 4 women with a mean age of 76.2 years (range: 59–86 years). Fusion images were created from three-dimensional time of flight (3D-TOF) MRA and 3D-FIESTA with phase cycling (3D-FIESTA-C). Then thrombectomy was performed in all the 5 patients. Merci retriever to 1 patient, Penumbra system to 1, urokinase infusion to 2, and Solitaire to 1 using such techniques. In all cases, a 3D-FIESTA-MRA fusion imaging could depict approximately clear vascular information to at least the M3 segment beyond the occlusion. And each acute revascularization was able to perform smoothly using these imaging techniques. In all cases, there was no symptomatic hemorrhagic complication. It showed that 3D-FIESTA MRA fusion imaging technique could obtain vascular information beyond the MCA occlusion. In this study, no symptomatic hemorrhagic complications were detected. It could imply that such techniques were useful not only to improve treatment efficiency but also to reduce the risk of development of hemorrhagic complications caused by vessel perforations in acute revascularization. PMID:26369877

  13. Angina induced by 5-fluorouracil infusion in a patient with normal coronaries.

    PubMed

    Tajik, Reza; Saadat, Habib; Taherkhani, Maryam; Movahed, Mohammad Reza

    2010-01-01

    This article reviews the occurrence of angina in patients treated with 5-fluorouracil (5-FU) without significant coronary artery disease. We present a case followed by a review of the literature. A 43-year-old man with a history of colon cancer developed typical angina during intravenous infusion of 5-FU. His electrocardiogram (ECG) showed tall T waves during his angina episode. His angina and ECG changes reoccurred during a second 5-FU infusion. His coronary angiography was normal. This case is consistent with a rare occurrence of 5-FU-induced angina despite normal coronaries. Physician should be aware of this important side effect of 5-FU infusion.

  14. [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.

  15. 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.

  16. [Intra-arterial fibrinolysis in acute thrombosis of the basilar artery].

    PubMed

    Solaz, J; Martínez-Rodrigo, J; Lonjedo, E; Poyatos, C; Vega, M; Palmero, J

    1998-12-01

    Ischemia in the territory of the basilar artery presents with a variable clinical picture of hemiparesia-tetraplegia, progressive deterioration of level of consciousness, irregular respiration and apnea leading to irreversible coma and death in between 75% and 86% of cases. The usual treatment is supportive. We present the case of a 49 year old woman with acute thrombosis of the basilar artery and a progressive course leading to coma. No bulbar lesions were seen on the CT scan done in the Emergency Department. Thrombosis of the basilar artery and permeable bilateral carotid systems were shown on arteriography. There were no contra-indications to fibrinolysis. Following local fibrinolytic treatment with urokinase the patient had full recovery from her neurological disorder and no sequelae. The basilar artery remained permeable six months later. Emergency treatment with cerebral intra-arterial fibrinolysis within the first six hours, in a case of neurological deficit progressing in the basilar artery territory, with persistence of brain-stem functions and no signs of decerebration (provided there are no contra-indications to fibrinolysis and the initial cerebral CT scan shows no bulbar lesions) may save the patient's life, with total or partial recovery of brain-stem function.

  17. Right Aortic Arch Detected Prenatally: A Rare Case With Bilateral Arterial Duct and Nonconfluent Pulmonary Arteries.

    PubMed

    Ricci, Silvia; Fainardi, Valentina; Spaziani, Gaia; Favilli, Silvia; Chiappa, Enrico

    2015-09-01

    We describe a rare case of right aortic arch (RAA) and nonconfluent pulmonary arteries. RAA and a right-sided arterial duct (AD) were identified on the prenatal scan, but a second left-sided AD and disconnection of the left pulmonary artery were missed. The missed diagnosis in fetal life adversely affected postnatal management. We suggest that fetuses with a prenatal diagnosis of RAA and right-sided AD be delivered in tertiary care centres to rule out an association with bilateral AD and nonconfluent pulmonary arteries after birth. Prompt postnatal diagnosis will enable preservation of flow in the disconnected pulmonary artery through prostaglandin E1 infusion until surgical reconstruction.

  18. Haemodynamic and cerebrovascular responses to glycerol infusion in dogs.

    PubMed

    Chen, J L; Wang, Y C; Wang, J Y

    1989-11-01

    1. The response of cerebral blood vessels to hyperosmolar agents in vivo remains controversial, and little is known about the effect of glycerol on cerebral vessels. In this study we investigated the cerebrovascular response to intravenous administration of glycerol (1 g/kg, infused over 25 min) in dogs under pentobarbital anaesthesia. 2. intracranial pressure, systemic arterial pressure, mean arterial blood pressure, serum osmolarity and packed cell volume were continuously monitored, and blood gases were checked frequently. Through a parietal cranial window, pial vessel diameter was measured by means of a surgical microscope and a video image-analyser. 3. Pial vessel diameter increased gradually with a maximum at 30 min after the beginning of glycerol infusion. The maximum increase in diameter in small (less than or equal to 100 microns) vessels was 14.3%, whereas that in large (greater than 100 microns) vessels was 10.3%. There was only a slight increase (less than 4%) in pial vessel diameter in vehicle-infused animals. The intracranial pressure decreased drastically after glycerol infusion, whereas the mean arterial blood pressure remained constant. There were correlations between the rise in serum osmolarity, fall in packed cell volume and vasodilatation, indicating that glycerol caused vasodilatation accompanied by plasma volume expansion. 4. Our data suggest that glycerol produces cerebral vasodilatation, which might be beneficial in cerebral ischaemia and vasospasm, in addition to its intracranial pressure-reducing effect on normal or oedematous brain. The degree of vasodilatation was not sufficient to affect the predominant intracranial pressure drop resulting from cerebral dehydration.

  19. Effects of systemic hyperthermia and intrahepatic infusion with 5-fluorouracil.

    PubMed

    Daly, J M; Smith, G; Frazier, O H; Dudrick, S J; Copeland, E M

    1982-03-15

    Potential hepatotoxicity from systemic hyperthermia (43 degrees C) +/- simultaneous hepatic artery infusion with 5-FU was evaluated in an animal model. Twenty-two dogs had aorta-vena caval shunts (8 mm Dacron grafts) placed, and 10 of these dogs had silastic catheters inserted in their hepatic arteries. Two weeks later, Group I (n = 8) was heated to 43 degrees C for one hour (distal esophageal + intrahepatic temperature) using the shunts and blood-heat exchangers; Group II (n = 6) was heated to 43 degrees C for one hour with simultaneous intrahepatic infusion of 5-FU (10 mg/kg); Group III (n = 8) was shamheated (37 degrees C) and underwent a one hour intrahepatic infusion with 5-FU (10 mg/kg). Serum alkaline phosphatase, SGOT, SPGT (IU/ml) and bilirubin were measured, and liver biopsies were obtained at 0 and 1 hour, at one and seven days. Mean SGOT levels increased significantly (P less than 0.05) in Group II from 19 +/- 2 to 31 +/- 6 and 63 +/- 18 at one hour and one day; these levels rose slightly in Group I from 31 +/- 5 to 40 +/- 8 and 47 +/- 8 at one hour and one day. Hepatocellular enzyme levels returned to normal at seven days in both groups. Mean SGOT and SGPT levels remained similar in Group III at all time periods. No significant differences in mean serum alkaline phosphatase or bilirubin levels were noted. There was no histologic evidence of hepatocellular necrosis at any time period. Survival was 6/8, 5/6 and 8/8 dogs in Groups I, II, and III, respectively. Systemic hyperthermia to 43 degrees C for one hour in dogs does not adversely affect serum hepatic enzymes or cell structure; reversible serum hepatic enzyme changes occurred when hyperthermia was combined with hepatic artery infusion with 5-FU.

  20. Hyperglycemia is associated with lower levels of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor in wound fluid.

    PubMed

    Akinci, Baris; Terzi, Cem; Sevindik, Gokmen; Yuksel, Faize; Tunc, Ulku Aybuke; Tunali, Sunay; Yesil, Sena

    2014-01-01

    Wounds in patients with hyperglycemia show impaired healing. Plasminogen activation is crucial in several overlapping phases of wound healing process. In this study, we aimed i) to compare acute wound fluid in patients with hyperglycemia and normoglycemia, ii) to focus on the elements of plasminogen activation in the wound fluid, and iii) to determine if the acute wound fluid characteristics are associated with surgical site infections. In a cohort of 54 patients, a closed suction drain was placed in the wound above the anterior abdominal wall fascia under the skin in order to collect postoperative acute wound fluid samples for 3 following days after colorectal surgery. Patients were classified as normoglycemic (n=25) or hyperglycemic (n=29; 17 with type 2 diabetes and 12 with stress induced hyperglycemia). Surgical site infection was defined according to the Centers for Disease Control criteria. The levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAr), plasminogen activator inhibitor-1 (PAI-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and fibroblast growth factor-1 (FGF-1) were measured in the wound fluid. Compared to normoglycemic subjects, patients with hyperglycemia had significantly lower levels of uPA and uPAr in the wound fluid despite similar or even higher circulating levels. There was no significant difference in IL-1β, TNF-α, PAI-1 and FGF-1 levels. In the whole study population, the wound fluid levels of uPA and uPAr were negatively correlated with circulating glucose levels. No difference was detected in the wound fluid characteristics of patients with and without surgical site infection. Patients with hyperglycemia exhibit decreased levels of uPA and uPAr in the wound fluid, suggesting a local failure in plasminogen activation at the wound site. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Osteopontin induces soluble urokinase-type plasminogen activator receptor production and release.

    PubMed

    Vaschetto, R; Navalesi, P; Clemente, N; Boggio, E; Valsecchi, S; Olivieri, C; Soluri, M F; Kroumova, V; Fonio, P; Dinatale, C; Borrè, S; Fortina, G; Umberto, D; Della Corte, F; Chiocchetti, A

    2015-02-01

    Osteopontin (OPN) and soluble urokinase plasminogen activator receptor (suPAR) have been proposed as markers of disease severity and risk-stratification in infection and inflammation. In breast cancer, OPN and the membrane bound form of urokinase plasminogen activator receptor (uPAR) are functionally related, as OPN-induced cell migration depends on uPAR triggering by urokinase plasminogen activator (uPA). The aim of this study was to prospectively evaluate the kinetic of OPN and suPAR blood levels in patients developing septic shock (SS) compared to those not developing SS, and to investigate the relationships between these two biomarkers in immune cells in vitro. We measured the levels of OPN and suPAR for 15 days in forty-three patients, defined a priory as at risk to develop septic shock. Moreover, we investigated in vitro the effect of recombinant OPN on uPAR and suPAR expression in monocytes. We found that OPN and suPAR levels were directly correlated to each other both at intensive care unit admission and on the day patients met SIRS/sepsis or septic shock criteria. In patients developing septic shock, OPN increased prior to suPAR and was already detectable up to 4 days before the shock development. In vitro, OPN induced suPAR production in monocytes by increasing both uPAR gene expression, and suPAR release from the cell surface. These data suggest that OPN is partly responsible for the increased plasma levels of suPAR and might be a valuable tool to predict the occurrence of septic shock.

  2. Geometry of GPPE binding to picrate and to the urokinase type plasminogen activator.

    PubMed

    Zesławska, Ewa; Stürzebecher, Jörg; Oleksyn, Barbara J

    2007-11-15

    Crystal structure of 2-(4-guanidynephenyl)-1-phenyl-ethanone (GPPE) in two different environments was determined in order to compare the binding geometry of these compound to a simple picrate anion and to protein, urokinase-type plasminogen activator (uPA), which may be treated as a target for anti-cancer drugs. It was shown that the conformation and the hydrogen-bonding formation by GPPE molecule are similar in both environments, but several important differences were discovered and described.

  3. Effects of hyperosmotic mannitol infusion on hemodynamics of dog kidney.

    PubMed

    Behnia, R; Koushanpour, E; Brunner, E A

    1996-05-01

    This study evaluated the effect of systemic infusion of hypertonic mannitol on renal hemodynamics (aortic pressure [P]-renal blood flow [RBF] relationship, glomerular filtration rate [GFR], and effective renal plasma flow [ERPF]) during 50% reduction of left kidney blood flow. Conditioned mongrel dogs anesthetized with halothane were hydrated by continuous infusion of lactated Ringer's solution containing creatinine to measure GFR and p-aminohippurate (PAH), to measure ERPF. The left kidney was exposed and two hydraulic occluders were placed, one around the aorta just above the renal arteries and the other around the left renal artery. Experimental design consisted of measuring P near the left renal artery, RBF by electromagnetic flowmeter, and ERPF and GFR by clearance methods in both kidneys in response to stepwise reduction in the aortic pressure by aortic occlusion before and after 50% reduction in the left kidney blood flow. The P-RBF relationship, GFR, and ERPF thus obtained were compared with those obtained during systemic intravenous infusion of 20% mannitol for a period of 1 h. We found that 1) a transient increase occurred in RBF with step reduction of P from 80 to 60 mm Hg under control conditions; 2) reducing the RBF by 50% changed the shape of the P-RBF relationship from a convex to the P axis to a linear form with a marked shift toward the P axis; 3) infusion of mannitol, during reduced RBF, caused a significant shift of the P-RBF curve toward the RBF axis and returned the linear P-RBF relationship toward normal, but had no effect on altered yield pressure; and 4) infusion of hypertonic mannitol had slightly increased GFR and ERPF in the right (unconstricted) kidney. However, hypertonic mannitol significantly increased GFR and ERPF values in the left (constricted) kidney suggesting a beneficial effect of mannitol on ischemic kidney. The results are consistent with the hypothesis that infusion of hypertonic mannitol to ischemic kidney increases RBF

  4. Breadboard development of a fluid infusion system

    NASA Technical Reports Server (NTRS)

    Thompson, R. W.

    1974-01-01

    A functional breadboard of a zero gravity Intravenous Infusion System (IVI) is presented. Major components described are: (1) infusate pack pressurizers; (2) pump module; (3) infusion set; and (4) electronic control package. The IVI breadboard was designed to demonstrate the feasibility of using the parallel solenoid pump and spring powered infusate source pressurizers for the emergency infusion of various liquids in a zero gravity environment. The IVI was tested for flow rate and sensitivity to back pressure at the needle. Results are presented.

  5. 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

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

    PubMed

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

    2014-09-15

    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. Copyright © 2014 the American Physiological Society.

  7. Protein delivery with infusion pumps.

    PubMed

    Bremer, U; Horres, C R; Francoeur, M L

    1997-01-01

    When a therapeutic effect is optimized by precise control of specific temporal patterns of plasma levels, infusion offers distinct advantages over oral administration, bolus injection, or depot delivery of polypeptides. The limitations of oral delivery are well known, and although research is under way into development of carrier systems that prevent degradation of labile agents, it is unlikely that the variances in absorption will meet the need for precise control. Depot delivery from subcutaneous or intramuscular implants presents a difficult situation when local tissue reactions to the agent sometimes occur. Removal of a depot system in the event of adverse reactions presents additional difficulties. Bolus injections are unable to sustain constant plasma levels unless the drug half-life is long or the injections are frequently administered. Insulin injections, for example, would be required every 30-60 minutes to approximate the plasma levels provided by a continuous infusion; such frequent injections would not be practical on a 24-hour basis. For the developer of new polypeptides, parenteral administration offers the most direct route to the marketplace. The step from periodic injections to tightly controlled infusion is a logical progression as compared with modification of the molecules or vehicles to obtain equivalent profiles. In Table II several different types of devices that can be used for infusion of proteins are compared. Microelectronics have played a major role in the miniaturization of infusion devices and undoubtedly will continue to do so. Micromachining, a spin-off technology of integrated circuit manufacture, will also find application in small infusion devices. In the future, we will have cost-effective disposable devices (Saaman et al., 1994) built on this technology that are programmable and thus can be adapted to meet each individual therapeutic need (Horres, 1994). We can also expect to see more closed-loop drug delivery systems where

  8. 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.

  9. Pathways of Infusate Loss During Convection Enhanced Delivery into the Putamen Nucleus

    PubMed Central

    Brady, Martin L.; Raghavan, Raghu; Alexander, Andrew; Kubota, Ken; Sillay, Karl; Emborg, Marina E.

    2013-01-01

    Background New strategies aiming to treat Parkinson’s disease such as delivery of trophic factors via protein infusion or gene transfer depend upon localized intracerebral infusion, mainly into the putamen nucleus. Convection enhanced delivery (CED) has been proposed as method to improve intracerebral distribution of therapies. Yet analysis of controversial results during the clinical translation of these strategies suggests that intracerebral misdistribution of infusate may have affected the outcomes by limiting the amount of treatment into the target region. Objectives This study aimed to identify possible pathways of infusate loss and their relative impact in the success of targeted CED into the postcommisural ventral putamen nucleus. Methods Thirteen adult macaque monkeys received under intraoperative magnetic resonance imaging (MRI) guidance, intraputaminal CED infusions of 100 μl of 2.0 mM gadoteridol and bromophenol blue (0.16 mg/ml) solution at a rate of 1.0 μl/min. Quantitative maps of infusate concentration were computed at 10 minute intervals throughout the procedure in a 3T MRI. The fraction of tracer lost from the putamen and as well as the path of loss was evaluated and quantified for each infusion. Results All injections (total 22) were successfully placed in the ventral postcommisural putamen nucleus. Four major paths of infusate loss from the putamen were observed: overflow across putamen boundaries, perivascular flow along large blood vessels, backflow along the inserted catheter and catheter tract leakage into the vacated catheter tract upon catheter removal. Overflow loss was observed within the first 30 μl of infusion in all cases. Measurable tracer loss following the path of an artery out of the putamen was observed in 15 cases, and in eight of these cases the loss was greater than 10% of infusate. Backflow that exited the putamen was observed in 4 cases and led to large loss of infusate (80% in one case) into the corona radiata. Loss

  10. Chorioamnionitis induced by subchorionic endotoxin infusion in sheep.

    PubMed

    Moss, Timothy J M; Nitsos, Ilias; Newnham, John P; Ikegami, Machiko; Jobe, Alan H

    2003-12-01

    This study was undertaken to determine whether subchorionic endotoxin infusion causes chorioamnionitis and preterm lung maturation, as occurs after intra-amniotic endotoxin. From day 118 of pregnancy, sheep received infusions of endotoxin (subchorionic 7.5 mg/d, n=11; intra-amniotic 2.5 mg/d, n=9) until delivery of lambs at 120 or 124 days. Other sheep received a single intra-amniotic injection of endotoxin (10 mg, n=7) at 118 days before delivery at 124 days. Controls (n=9) received equivalent saline solution treatments. Chorioamnionitis accompanied all endotoxin treatments. Lung inflammation occurred after intra-amniotic endotoxin infusion or injection but not after subchorionic endotoxin. Umbilical arterial pH was lower and Pco(2) was higher than control after subchorionic endotoxin. Lung compliance and surfactant were increased after intra-amniotic endotoxin infusion or injection but not after subchorionic endotoxin. Chorioamnionitis may result from inflammatory stimuli at various intrauterine sites, with different sites causing different fetal effects and not all cases of chorioamnionitis being accompanied by enhanced lung maturation.

  11. Urokinase Receptor Cleavage: A Crucial Step in Fibroblast-to-Myofibroblast Differentiation

    PubMed Central

    Twining, Sally S.; Warejcka, Debra J.; Tall, Edward; Masur, Sandra K.

    2007-01-01

    Fibroblasts migrate into and repopulate connective tissue wounds. At the wound edge, fibroblasts differentiate into myofibroblasts, and they promote wound closure. Regulated fibroblast-to-myofibroblast differentiation is critical for regenerative healing. Previous studies have focused on the role in fibroblasts of urokinase plasmingen activator/urokinase plasmingen activator receptor (uPA/uPAR), an extracellular protease system that promotes matrix remodeling, growth factor activation, and cell migration. Whereas fibroblasts have substantial uPA activity and uPAR expression, we discovered that cultured myofibroblasts eventually lost cell surface uPA/uPAR. This led us to investigate the relevance of uPA/uPAR activity to myofibroblast differentiation. We found that fibroblasts expressed increased amounts of full-length cell surface uPAR (D1D2D3) compared with myofibroblasts, which had reduced expression of D1D2D3 but increased expression of the truncated form of uPAR (D2D3) on their cell surface. Retaining full-length uPAR was found to be essential for regulating myofibroblast differentiation, because 1) protease inhibitors that prevented uPAR cleavage also prevented myofibroblast differentiation, and 2) overexpression of cDNA for a noncleavable form of uPAR inhibited myofibroblast differentiation. These data support a novel hypothesis that maintaining full-length uPAR on the cell surface regulates the fibroblast to myofibroblast transition and that down-regulation of uPAR is necessary for myofibroblast differentiation. PMID:17507651

  12. [Urokinase as a blood and urine plasminogen activator in chronic glomerulonephritis and amyloidosis].

    PubMed

    Andreenko, G V; Poliantseva, L R; Podorol'skaia, L V; Bumblite, I D

    1999-01-01

    To estimate the individual role of the plasminogen activators (PA) urokinase (u-PA) and tissue (t-PA) in the development of two renal diseases (the nephrotic forms of chronic glomerulonephritis (CGN) and amyloidosis, the baseline plasma and urine levels of u-PA and t-PA antigens, their functional activity (FPAA), and changes in these parameters were determined after protein loading test (0.7 g/kg). In healthy individuals and patients with amyloidosis, the baseline FPAA changes from 0 to the maximum were caused only by the alterations of u-PA levels, in those with CGN, they were induced by the changes in the content of u-PA and t-AP antigens. The functional loading test revealed PA reserves solely in patients having a high baseline FPAA for both nephropathies: u-PA in amyloidosis and t-PA in CGN. In all the patients, the urine levels of u-PA antigens were 20-40 times more than those of t-PA antigens and 5-6 times less than those plasma u-PA. The findings suggest that urokinase may be regarded as the major plasminogen activator involved in CGN and amyloidosis.

  13. Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer

    PubMed Central

    Montuori, Nunzia; Pesapane, Ada; Rossi, Francesca W; Giudice, Valentina; De Paulis, Amato; Selleri, Carmine; Ragno, Pia

    2016-01-01

    The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored receptor that focuses urokinase (uPA) proteolytic activity on the cell surface. uPAR also regulates cell adhesion, migration and proliferation, protects from apoptosis and contributes to epithelial mesenchymal transition (EMT), independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2 and beta3 integrins, thus regulating their activities. uPAR cross-talks with receptor tyrosine kinases through integrins and regulates cancer cell dormancy, proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association with fMLF-receptors (fMLF-Rs). Further, uPAR is an adhesion receptor because it binds vitronectin (VN), a component of provisional extracellular matrix. High uPAR expression predicts for more aggressive disease in several cancer types for its ability to increase invasion and metastasis. In fact, uPAR has been hypothesized to be the link between tumor cell dormancy and proliferation that usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a feasible approach to affect tumor growth and metastasis. Here, we review the more recent advances in the development of uPAR-targeted anti-cancer therapeutic agents suitable for further optimization or ready for the evaluation in early clinical trials. PMID:27896223

  14. [The intraosseous infusion in adult].

    PubMed

    Plancade, D; Rüttimann, M; Wagnon, G; Landy, C; Schaeffer, E; Gagnon, N; Nadaud, J; Favier, J-C

    2013-05-01

    Intraosseous infusion is an old knowledge, abandoned in the 1950s in favor of the peripheral vein, and it was essentially described in pediatrics and military medicine. Since 2005, this way is experiencing a resurgence of interest in emergency medicine particularly in adults after the failure's installation of a peripheral vein in order not to waste the time of care and administration of treatment. New devices that allow intraosseous infusion are currently used in humans. We propose to review the different kind of catheters used, to know the main technical characteristics, indications, contraindications and potential complications. We propose a comparison with the peripheral vein and a comparison between the different catheters.

  15. [The effect of low molecular heparin and urokinase on MCP-1 of acute experimental pulmonary embolism in rabbits].

    PubMed

    Yu, Hongzhi; Wu, Qi; Wu, Junping; Sun, Xin; Du, Zhongzhen; Li, Li; Wu, Qian

    2014-06-01

    To evaluate effect the of thrombolytic (urokinase, UK) and anticoagulant agent (low-molecular-weight heparin, LMWH) on the pulmonary injury of rabbits with acute pulmonary embolism (PE) by assaying monocyte chemoattractant protein-1 (MCP-1). Rabbit models with PE were established by transfusing autologous blood clots on 60 healthy male Japanese white rabbits. Experimental PE rabbits were randomly divided into 3 groups:normal saline (NS) group (n = 18) , LMWH group (n = 18) and UK group (n = 18), and other 18 rabbits underwent sham operations as SHAM group (n = 18). Each group was divided into 3 subgroups based on 2 days (day 2), 4 days (day 4), and 14 days (day 14) after therapies. Arterial blood gas analysis was measured. MCP-1 levels in lung tissue and blood were assayed with ELISA at various times (day 2, day 4 and day 14 ). Fixed sections were stained with trichrome for intimal hyperplasia determination. The overall rate of success for making PE rabbit models was 90% (54/60), which was not affected by treatment. Compared with NS group, P(A-a)O2 significantly decreased in UK group. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in LMWH group on day 4 [(33 ± 9) ng/L vs (48 ± 5) ng/L, P < 0.05] and day 14 [(30 ± 11) ng/L vs (41 ± 4) ng/L, P < 0.05]; MCP-1 levels in serum on day 14 also significantly decreased in LMWH group [(36 ± 10) ng/L vs (51 ± 5) ng/L, P < 0.05]. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in UK group on day 2 and 4 [Day 2: (34 ± 8) ng/L vs (50 ± 4) ng/L, P < 0.05; Day 4: (29 ± 7) ng/L vs (48 ± 5) ng/L, P < 0.05]; MCP-1 levels in serum on day 2 and day 4 also significantly decreased in UK group [Day 2: (44 ± 3) ng/L vs (48 ± 3) ng/L, P < 0.05; Day 4: (44 ± 4) ng/L vs (53 ± 1)ng/L, P < 0.05]. UK treatment may rapidly improve V/Q ratio and decrease MCP-1 levels in lung tissue or serum, but it can not inhibit persistent inflammation. LMWH can decrease MCP-1 levels in lung

  16. 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.

  17. Use of Continuous Infusion Hydralazine in a Pediatric Patient on Mechanical Circulatory Support

    PubMed Central

    Dillman, Nicholas O.; Anders, Marc M.

    2016-01-01

    Hydralazine is a direct peripheral arterial vasodilator used for acute hypertension. Usually administered as a bolus dose, continuous infusion has been described during pregnancy for preeclampsia and eclampsia and in limited reports in cardiac surgeries for afterload reduction. This case describes the use of continuous infusion hydralazine for afterload reduction in an infant receiving extracorporeal membrane oxygenation (ECMO) post–cardiac surgery. Postsurgery, the patient's mean arterial pressures (MAPs) could not be controlled despite escalating doses of vasodilatory medications including nitroprusside, nicardipine, and milrinone; hence, continuous infusion hydralazine was initiated. Although the initiation of a hydralazine infusion produced a decrease in MAP, the response was unsustainable. This case highlights an alternative method for managing systemic vascular resistance and cardiac output to allow for myocardial recovery after cardiac surgery and use of extracorporeal support. At the time of this writing, this is the first published case describing hydralazine administration via continuous infusion in pediatric patients. The use of continuous infusion hydralazine for afterload reduction provided a brief, non-sustained reduction in MAP in a post–cardiac surgery infant managed on ECMO support. PMID:27453704

  18. Infusing Technology throughout Teacher Education.

    ERIC Educational Resources Information Center

    Maliski, Susanne; Bartell, Carol; Gathercoal, Paul

    This paper reports on overall accomplishments in meeting goals for technology infusion at California Lutheran University's School of Education, using evaluation data collected over 3 years. Data came from surveys completed by administrators, faculty, and students about their experiences using technology at baseline (1997) and over the next 3…

  19. 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…

  20. 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…

  1. 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…

  2. Microcomputer Infusion Project: A Model.

    ERIC Educational Resources Information Center

    Rossberg, Stephen A.; Bitter, Gary G.

    1988-01-01

    Describes the Microcomputer Infusion Project (MIP), which was developed at Arizona State University to provide faculty with the necessary hardware, software, and training to become models of computer use in both lesson development and presentation for preservice teacher education students. Topics discussed include word processing; database…

  3. 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.

  4. 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.

  5. Effect of calcium gluconate infusion on renin in the dog.

    PubMed

    Kotchen, T A; Maull, K I; Kotchen, J M; Luke, R G

    1977-01-01

    We have previously reported that infusion of CaCl2 into the renal artery of the dog inhibits renin release. To evaluate the possible importance of the anion delivered with calcium, similar experiments were performed in 10 dogs with equivalent amounts of calcium gluconate (0.3 mg. of Ca++ per kilogram of body weight per minute). The experiment consisted of three successive 15 minute control periods, followed by three 15 minute calcium gluconate infusion periods and two 15 minute recovery periods. During calcium gluconate infusion, mean serum Ca++, and ECa++, ENa+, and EFNa+ from the infuses kidney increased (p less than 0.005). Systolic blood pressure (142 mm. Hg +/- 8S.E.), renal blood flow (137 ml. per minute +/- 11 S.E.), creatinine clearance, and aldosterone excretion (12.0 ng. per 15 minute +/- 1.5 S.E.) did not change (p less than 0.3). Renal venous PRA (28.4 ng. per millileter per hour +/- 7.5 S.E.) decreased (p less than 0.014). The per cent decrease of PRA correlated (r = -0.70) with the per cent increase EFNa+ (p less than 0.001). Calcium gluconate had a lesser (p less than 0.01) inhibitory effect on renin than CaCl2, despite greater excretion of Ca++ and Na++ during calcium gluconate infusion. Taken together, the results indicate that Ca++ inhibits renin release, although the extent of the inhibition is modified by the anion accompanying Ca++. The effect of Ca++ on renin may be mediated by NaCl transport across the macula densa.

  6. Water intoxication associated with oxytocin infusion

    PubMed Central

    Ahmad, Audrey J.; Clark, Elizabeth H.; Jacobs, Howard S.

    1975-01-01

    During a mid-trimester abortion with high dose oxytocin infusion and intravenous fluids, a patient developed an acute dilutational hyponatraemia and coma. The relationship of water intoxication and synthetic oxytocin infusion is discussed and the literature reviewed. PMID:1197156

  7. A Case of Coronary Vasospasm after Repeat Rituximab Infusion

    PubMed Central

    Ke, Calvin; Khosla, Amit; Davis, Margot K.; Hague, Cameron; Toma, Mustafa

    2015-01-01

    Coronary artery vasospasm (CAV) can be triggered by medication reactions. CAV occurring after multiple exposures to rituximab has not been previously described. A 61-year-old woman with no cardiac risk factors was treated with the sixth cycle of gemcitabine, cisplatin, dexamethasone, and rituximab therapy. Fifteen minutes after rituximab infusion commenced, she developed typical cardiac chest pain with ST segment elevations on electrocardiogram. Angiogram revealed evidence of coronary vasospasm. The patient was successfully treated with amlodipine. This case underlines the importance of monitoring cardiac side effects of rituximab therapy, even after multiple cycles. PMID:25866684

  8. Slow infusion rate of doxorubicin induces higher pro-inflammatory cytokine production.

    PubMed

    Tien, Chin-Chieh; Peng, Yi-Chi; Yang, Fwu-Lin; Subeq, Yi-Maun; Lee, Ru-Ping

    2016-11-01

    Different infusion rates of doxorubicin (DOX) have been used for treating human malignancies. Organ toxicity after DOX infusion is a major issue in treatment disruption. However, whether different DOX infusion rates induce different toxicity is still unknown. In this study, we examined the toxicity effects of different DOX infusion rates in the early phase of organ toxicity. Thirty-six rats were randomly divided into 5-, 15-, and 30-min infusion rate groups. A single dose of DOX (8.3 mg/kg, I.V.) was administered at different infusion rates. Blood samples were collected from the femoral artery at 1, 3, 6, 9, 12, 18, 24, 36, and 48 h after DOX administration. The blood cell count and blood biochemistry were analyzed. The liver, kidney, and heart were removed for pathological examinations after the rats were sacrificed. Our findings show that the 30-min group had higher injury markers in the liver (glutamic oxaloacetic transaminase and glutamic pyruvic transaminase), kidneys (blood urea nitrogen and creatinine), and heart (creatine phosphokinase-MB and lactate dehydrogenase), and had higher tumor necrosis factor-alpha and interleukin 6 levels than did the other groups. The 30-min group also had more severe damage according to the pathological examinations. In conclusion, slower infusion of DOX induced a higher inflammatory response and greater organ damage.

  9. Tachyphylaxis and sensitization to nicotine-induced tachycardiac and pressor effects after nicotine infusions.

    PubMed

    Cruz, S L; Vidrio, H

    1997-01-01

    This work examined the effects of nicotine on mean arterial pressure and heart rate in non-anesthetized spinal rats. Nicotine (200 mg/kg) was administered as a single bolus, as infusions lasting 7.5, 15 or 30 min, and as a post-infusion bolus. A nicotine bolus increased pressure and rate. These effects were less marked as the rate of infusion decreased. The infusions affected differentially the effects of a subsequent bolus. Thus, while tachycardia was decreased, the blood pressure rise was increased. An initial transient bradycardia was observed after bolus administration, but not during infusions; this effect was unchanged after post-infusion boluses. Pharmacological analysis indicated that tachycardia and bradycardia were predominantly due to ganglionic stimulation, while adrenal and sympathetic nerve catecholamine release played a major role in the pressor response. These results indicate that slow nicotine infusions do not induce tachyphylaxis for all of the cardiovascular effects of a subsequent bolus, and that development of acute tolerance appears to depend on the mechanism of action of the response.

  10. 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 a...

  11. 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... 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 a...

  12. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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 a... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Infusion pump. 880.5725 Section 880.5725 Food...

  13. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 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 a... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Infusion pump. 880.5725 Section 880.5725 Food...

  14. 21 CFR 880.5725 - Infusion pump.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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 a... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Infusion pump. 880.5725 Section 880.5725 Food...

  15. Monocyte-expressed urokinase inhibits vascular smooth muscle cell growth by activating Stat1.

    PubMed

    Kunigal, Sateesh; Kusch, Angelika; Tkachuk, Natalia; Tkachuk, Sergey; Jerke, Uwe; Haller, Hermann; Dumler, Inna

    2003-12-15

    After vascular injury, a remodeling process occurs that features leukocyte migration and infiltration. Loss of endothelial integrity allows the leukocytes to interact with vascular smooth muscle cells (VSMCs) and to elicit "marching orders"; however, the signaling processes are poorly understood. We found that human monocytes inhibit VSMC proliferation and induce a migratory potential. The monocytes signal the VSMCs through the urokinase-type plasminogen activator (uPA). The VSMC uPA receptor (uPAR) receives the signal and activates the transcription factor Stat1 that, in turn, mediates the antiproliferative effects. These results provide the first evidence that monocytes signal VSMCs by mechanisms involving the fibrinolytic system, and they imply an important link between the uPA/uPAR-related signaling machinery and human vascular disease.

  16. Urokinase plasminogen activator receptor: a functional integrator of extracellular proteolysis, cell adhesion, and signal transduction.

    PubMed

    Ferraris, Gian Maria Sarra; Sidenius, Nicolai

    2013-06-01

    The urokinase plasminogen activator receptor (uPAR) is a cell surface receptor involved in a multitude of physiologic and pathologic processes. uPAR regulates simultaneously a branch of the plasminogen activator system and modulates cell adhesion and intracellular signaling by interacting with extracellular matrix components and signaling receptors. The multiple uPAR functions are deeply interconnected, and their integration determines the effects that uPAR expression triggers in different contexts. The proteolytic function of uPAR affects both the signaling and the adhesive functions of the receptor, whereas these latter two are closely interconnected. This review focuses on the molecular mechanisms that connect and mutually regulate the different uPAR functions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. [Thrombolytic efficacy of a Lys-plasminogen-urokinase combination: studies in experimental animals and humans].

    PubMed

    Latorre, J; Foncuberta, J; Rosendo, A; Elez, J

    1990-01-01

    During animal experimental phase, lis-pg combined with UK produced a thrombolysis of about a 62.5%. This effect is accompanied by an important fibrinolytic system activation, a decrease in fibrinogen levels (0.37 +/- 0.2 gr/l) and an increase PDF/Fg (120.5 +/- 30 ng/ml). Such thrombolytic stage produced diverse hemorrhagic complications in experimental animals. During human clinical trial stage, then patients with Deep Venous Thrombosis (DVT) at proximal lower limbs level were submitted to diverse treatment protocols with Lis-Plasminogen (Lis-plg) and Urokinase (UK). After preliminary outcomes we can conclude that administration of Lis-plg followed by UK increases the fibrinolytic activity but also increases the risk of hemorrhagic complications. This second effect is not probably caused by an specific absorption on the thrombo surface, but by an increase of circulating plasminogen levels Lis-plg exogenous-induced.

  18. Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells

    PubMed Central

    1987-01-01

    Cellular migration is an essential component of invasive biological processes, many of which have been correlated with an increase in plasminogen activator production. Endothelial cell migration occurs in vivo during repair of vascular lesions and angiogenesis, and can be induced in vitro by wounding a confluent monolayer of cells. By combining the wounded monolayer model with a substrate overlay technique, we show that cells migrating from the edges of an experimental wound display an increase in urokinase-type plasminogen activator (uPA) activity, and that this activity reverts to background levels upon cessation of movement, when the wound has closed. Our results demonstrate a direct temporal relationship between endothelial cell migration and uPA activity, and suggest that induction of uPA activity is a component of the migratory process. PMID:3121633

  19. Urokinase Plasminogen Activator Receptor (uPAR) Targeted Nuclear Imaging and Radionuclide Therapy

    PubMed Central

    Li, Dan; Liu, Shuanglong; Shan, Hong; Conti, Peter; Li, Zibo

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein. Besides regulating proteolysis, uPAR could also activate many intracellular signaling pathways that promote cell motility, invasion, proliferation, and survival through cooperating with transmembrane receptors. uPAR is overexpressed across a variety of tumors and is associated with cancer invasion and metastasis. In order to meet the demand for a rapid development and potential clinical application of anti-cancer therapy based on uPA/uPAR system, it is desirable to develop non-invasive imaging methods to visualize and quantify uPAR expression in vivo. In this review, we will discuss recent advances in the development of uPAR-targeted nuclear imaging and radionuclide therapy agents. The successful development of molecular imaging probes to visualize uPAR expression in vivo would not only assist preclinical researches on uPAR function, but also eventually impact patient management. PMID:23843898

  20. Primary focal and segmental glomerulosclerosis and soluble factor urokinase-type plasminogen activator receptor

    PubMed Central

    Trimarchi, Hernán

    2013-01-01

    Primary focal and segmental glomerulosclerosis (FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy. PMID:24255893

  1. Imaging of Prostate Cancer Using Urokinase-Type Plasminogen Activator Receptor PET.

    PubMed

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2017-04-01

    Urokinase-type plasminogen activator receptor (uPAR) overexpression is an important biomarker for aggressiveness in cancer including prostate cancer (PC) and provides independent clinical information in addition to prostate-specific antigen and Gleason score. This article focuses on uPAR PET as a new diagnostic and prognostic imaging biomarker in PC. Many preclinical uPAR-targeted PET imaging studies using AE105 in cancer models have been undertaken with promising results. A major breakthrough was obtained with the recent human translation of uPAR PET in using (64)Cu- and (68)Ga-labelled versions of AE105, respectively. Clinical results from patients with PC included in these studies are encouraging and support continuation with large-scale clinical trials.

  2. Microcirculatory Response In Vivo on Local Intraarterial Infusion of Autogenic Adipose-derived Stem Cells or Stromal Vascular Fraction.

    PubMed

    Wang, Wei Z

    2016-09-01

    Both adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) have been demonstrated to have regenerative properties with therapeutic potential for numerous diseases through local or topical applications. However, it is unclear whether ASC or SVF can be delivered systemically through an intra-arterial infusion. The purpose of this study was to examine the microcirculatory response in vivo on local intraarterial infusion of autogenic ASCs or SVF in a vascular pedicle isolated rat cremaster microcirculation model.

  3. Endotoxin induction of an inhibitor of plasminogen activator in bovine pulmonary artery endothelial cells

    SciTech Connect

    Not Available

    1986-01-05

    The effects of bacterial lipopolysaccharide (endotoxin) on the fibrinolytic activity of bovine pulmonary artery endothelial cells were examined. Endotoxin suppressed the net fibrinolytic activity of cell extracts and conditioned media in a dose-dependent manner. The effects of endotoxin required at least 6 h for expression. Cell extracts and conditioned media contained a 44-kDa urokinase-like plasminogen activator. Media also contained multiple plasminogen activators with molecular masses of 65-75 and 80-100 kDa. Plasminogen activators in extracts and media were unchanged by treatment of cells with endotoxin. Diisopropyl fluorophosphate (DFP)-abolished fibrinolytic activity of extracts and conditioned media. DFP-treated samples from endotoxin-treated but not untreated cells inhibited urokinase and tissue plasminogen activator, but not plasmin. Inhibitory activity was lost by incubation at pH 3 or heating to 56/sup 0/C for 10 min. These treatments did not affect inhibitory activity of fetal bovine serum. Incubation of /sup 125/I-urokinase with DFP-treated medium from endotoxin-treated cells produced an inactive complex with an apparent molecular mass of 80-85 kDa.

  4. The fibrogenic actions of lung fibroblast-derived urokinase: a potential drug target in IPF

    PubMed Central

    Schuliga, Michael; Jaffar, Jade; Harris, Trudi; Knight, Darryl A; Westall, Glen; Stewart, Alastair G

    2017-01-01

    The role of urokinase plasminogen activator (uPA) in idiopathic pulmonary fibrosis (IPF) remains unclear. uPA-generated plasmin has potent fibrogenic actions involving protease activated receptor-1 (PAR-1) and interleukin-6 (IL-6). Here we characterize uPA distribution or levels in lung tissue and sera from IPF patients to establish the mechanism of its fibrogenic actions on lung fibroblasts (LFs). uPA immunoreactivity was detected in regions of fibrosis including fibroblasts of lung tissue from IPF patients (n = 7). Serum uPA levels and activity were also higher in IPF patients (n = 18) than controls (n = 18) (P < 0.05), being negatively correlated with lung function as measured by forced vital capacity (FVC) %predicted (P < 0.05). The culture supernatants of LFs from IPF patients, as compared to controls, showed an increase in plasmin activity after plasminogen incubation (5–15 μg/mL), corresponding with increased levels of uPA and IL-6 (n = 5–6, P < 0.05). Plasminogen-induced increases in plasmin activity and IL-6 levels were attenuated by reducing uPA and/or PAR-1 expression by RNAi. Plasmin(ogen)-induced mitogenesis was also attenuated by targeting uPA, PAR-1 or IL-6. Our data shows uPA is formed in active regions of fibrosis in IPF lung and contributes to LF plasmin generation, IL-6 production and proliferation. Urokinase is a potential target for the treatment of lung fibrosis. PMID:28139758

  5. Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors

    PubMed Central

    Rossmeisl, John H; Hall-Manning, Kelli; Robertson, John L; King, Jamie N; Davalos, Rafael V; Debinski, Waldemar; Elankumaran, Subbiah

    2017-01-01

    Background The expression of the urokinase plasminogen activator receptor (uPAR), a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA), have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis. The objective of this study was to characterize the expression of uPAR and the activity of uPA in canine brain tumors as justification for the development of uPAR-targeted brain tumor therapeutics in dogs. Methods We investigated the expression of uPAR in 37 primary canine brain tumors using immunohistochemistry, Western blotting, real-time quantitative polymerase chain reaction analyses, and by the assay of the activity of uPA using casein–plasminogen zymography. Results Expression of uPAR was observed in multiple tumoral microenvironmental niches, including neoplastic cells, stroma, and the vasculature of canine brain tumors. Relative to normal brain tissues, uPAR protein and mRNA expression were significantly greater in canine meningiomas, gliomas, and choroid plexus tumors. Increased activity of uPA was documented in all tumor types. Conclusions uPAR is overexpressed and uPA activity increased in canine meningiomas, gliomas, and choroid plexus tumors. This study illustrates the potential of uPAR/uPA molecularly targeted approaches for canine brain tumor therapeutics and reinforces the translational significance of canines with spontaneous brain tumors as models for human disease

  6. Intraventricular administration of urokinase as a novel therapeutic approach for communicating hydrocephalus.

    PubMed

    Feng, Zhou; Tan, Qiang; Tang, Jun; Li, Lin; Tao, Yihao; Chen, Yujie; Yang, Yunfeng; Luo, Chunxia; Feng, Hua; Zhu, Gang; Chen, Qianwei; Chen, Zhi

    2017-02-01

    Fibrosis of the subarachnoid space (SAS) after infection, inflammation, or hemorrhage can impair cerebrospinal fluid absorption and circulation, causing diffuse ventricular dilatation. In the present study, we tested the hypothesis that urokinase (also known as urokinase-type plasminogen activator [uPA]), a fibrinolytic agent, attenuates fibrosis and ventriculomegaly in a rat model of kaolin-induced communicating hydrocephalus and thus may have potential as a therapy for these conditions. Thirty microliters of sterile 25% kaolin suspension was injected into the basal cisterns of adult Sprague-Dawley rats to induce hydrocephalus, and 2 intraventricular injections of either uPA or vehicle (saline) were administered immediately and 3 days thereafter. Ventricular volumes were measured by magnetic resonance imaging (MRI) on days 3, 14, and 28 after kaolin injection. Fibrosis and reactive astrogliosis were evaluated on day 28 by immunofluorescence and Western blotting. Neurocognitive features were tested using the Morris water maze from days 23 to 28. MRI analysis demonstrated that kaolin administration successfully induced hydrocephalus in rats and that uPA treatment significantly attenuated ventricular enlargement. In addition, uPA inhibited the deposition of laminin and fibronectin, extracellular matrix molecules, in the SAS, attenuated gliosis, and improved learning and memory in kaolin-treated rats. Therefore, we concluded that uPA prevents the development of kaolin-induced communicating hydrocephalus by preventing the development of subarachnoid fibrosis and by eliciting improvements in neurocognition. The results of this study indicate that uPA may be a novel clinical therapy for communicating hydrocephalus.

  7. Participation of the urokinase-type plasminogen activator receptor (uPAR) in neutrophil transendothelial migration.

    PubMed

    Pliyev, Boris K; Antonova, Olga A; Menshikov, Mikhail

    2011-05-01

    The mechanisms underlying migration of neutrophils across endothelium are not completely understood. The urokinase-type plasminogen activator receptor (uPAR) plays a key role in neutrophil adhesion and migration. In the present study, we addressed whether uPAR regulates neutrophil transendothelial migration. We first showed that siRNA-mediated knockdown of uPAR in human umbilical vein endothelial cells (HUVECs) did not affect neutrophil migration across HUVEC monolayers indicating that endothelial uPAR does not regulate neutrophil transmigration. In contrast, the transmigration was significantly inhibited by Fab' fragment of anti-uPAR monoclonal antibody and proteolytically inactive urokinase (uPA), whereas inhibition of proteolytical activity of endogenous uPA (with amiloride or plasminogen activator inhibitor-1) did not affect the transmigration. Both the anti-uPAR Fab' fragment and proteolytically inactive uPA did not exert significant effects upon the transmigration conducted in the presence of F(ab')(2) fragment of blocking antibody to integrin Mac-1 indicating that uPAR regulates Mac-1-dependent transmigration. Mac-1-dependent, but not Mac-1-independent, transmigration was significantly reduced in the presence of N-acetyl-d-glucosamine and d-mannose, the saccharides that disrupt uPAR/Mac-1 association, but was unaffected in the presence of control saccharides (d-sorbitol and sucrose). We conclude that physical association of uPAR with Mac-1 mediates the regulatory effect of uPAR over the transmigration. Finally, we provide evidence that the functional cooperation between uPAR and Mac-1 is essential at both adhesion and diapedesis steps of neutrophil migration across endothelium. Thus, uPAR expressed on neutrophil plasma membrane regulates transendothelial migration independently of uPA proteolytical activity and acting as a cofactor for integrin Mac-1.

  8. Herbal compound triptolide synergistically enhanced antitumor activity of amino-terminal fragment of urokinase

    PubMed Central

    2013-01-01

    Background Urokinase (uPA) and its receptor (uPAR) play an important role in tumour growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumours. Targeting the excessive activation of this system as well as the proliferation of the tumour vascular endothelial cell would be expected to prevent tumour neovasculature and halt tumour development. The amino terminal fragment (ATF) of urokinase has been confirmed effective to inhibit the proliferation, migration and invasiveness of cancer cells via interrupting the interaction of uPA and uPAR. Triptolide (TPL) is a purified diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook F that has shown antitumor activities in various cancer cell types. However, its therapeutic application is limited by its toxicity in normal tissues and complications caused in patients. In this study, we attempted to investigate the synergistic anticancer activity of TPL and ATF in various solid tumour cells. Methods Using in vitro and in vivo experiments, we investigated the combined effect of TPL and ATF at a low dosage on cell proliferation, cell apoptosis, cell cycle distribution, cell migration, signalling pathways, xenograft tumour growth and angiogenesis. Results Our data showed that the sensitivity of a combined therapy using TPL and ATF was higher than that of TPL or ATF alone. Suppression of NF-κB transcriptional activity, activation of caspase-9/caspase-3, cell cycle arrest, and inhibition of uPAR-mediated signalling pathway contributed to the synergistic effects of this combination therapy. Furthermore, using a mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumour growth by inhibiting angiogenesis as compared with ATF or TPL treatment alone. Conclusions Our study suggests that lower concentration of ATF and TPL used in combination may produce a synergistic anticancer efficacy that warrants further

  9. Mis-trafficking of endosomal urokinase proteins triggers drug-induced glioma nonapoptotic cell death.

    PubMed

    Pasupuleti, Nagarekha; Grodzki, Ana Cristina; Gorin, Fredric

    2015-04-01

    5-Benzylglycinyl-amiloride (UCD38B) is the parent molecule of a class of anticancer small molecules that kill proliferative and nonproliferative high-grade glioma cells by programmed necrosis. UCD38B intracellularly triggers endocytosis, causing 40-50% of endosomes containing proteins of the urokinase plasminogen activator system (uPAS) to relocate to perinuclear mitochondrial regions. Endosomal "mis-trafficking" caused by UCD38B in human glioma cells corresponds to mitochondrial depolarization with the release and nuclear translocation of apoptotis-inducing factor (AIF) followed by irreversible caspase-independent cell demise. High-content quantification of immunocytochemical colocalization studies identified that UCD38B treatment increased endocytosis of the urokinase plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) into the early and late endosomes by 4- to 5-fold prior to AIF nuclear translocation and subsequent glioma demise. PAI-1 was found to comparably relocate with a subset of early and late endosomes in four different human glioma cell lines after UCD38B treatment, followed by caspase-independent, nonapoptotic cell death. Following UCD38B treatment, the receptor guidance protein LRP-1, which is required for endosomal recycling of the uPA receptor to the plasmalemma, remained abnormally associated with PAI-1 in early and late endosomes. The resultant aberrant endosomal recycling increased the total cellular content of the uPA-PAI-1 protein complex. Reversible inhibition of cellular endocytosis demonstrated that UCD38B bypasses the plasmalemmal uPAS complex and directly acts intracellularly to alter uPAS endocytotic trafficking. UCD38B represents a class of small molecules whose anticancer cytotoxicity is a consequence of causing the mis-trafficking of early and late endosomes containing uPAS cargo and leading to AIF-mediated necrotic cell death. Copyright © 2015 by The American Society for Pharmacology and

  10. Urokinase-Type Plasminogen Activator Promotes Dendritic Spine Recovery and Improves Neurological Outcome Following Ischemic Stroke

    PubMed Central

    Wu, Fang; Catano, Marcela; Echeverry, Ramiro; Torre, Enrique; Haile, Woldeab B.; An, Jie; Chen, Changhua; Cheng, Lihong; Nicholson, Andrew; Tong, Frank C.; Park, Jaekeun

    2014-01-01

    Spines are dendritic protrusions that receive most of the excitatory input in the brain. Early after the onset of cerebral ischemia dendritic spines in the peri-infarct cortex are replaced by areas of focal swelling, and their re-emergence from these varicosities is associated with neurological recovery after acute ischemic stroke (AIS). Urokinase-type plasminogen activator (uPA) is a serine proteinase that plays a central role in tissue remodeling via binding to the urokinase plasminogen activator receptor (uPAR). We report that cerebral cortical neurons release uPA during the recovery phase from ischemic stroke in vivo or hypoxia in vitro. Although uPA does not have an effect on ischemia- or hypoxia-induced neuronal death, genetic deficiency of uPA (uPA−/−) or uPAR (uPAR−/−) abrogates functional recovery after AIS. Treatment with recombinant uPA after ischemic stroke induces neurological recovery in wild-type and uPA−/− but not in uPAR−/− mice. Diffusion tensor imaging studies indicate that uPA−/− mice have increased water diffusivity and decreased anisotropy associated with impaired dendritic spine recovery and decreased length of distal neurites in the peri-infarct cortex. We found that the excitotoxic injury induces the clustering of uPAR in dendritic varicosities, and that the binding of uPA to uPAR promotes the reorganization of the actin cytoskeleton and re-emergence of dendritic filopodia from uPAR-enriched varicosities. This effect is independent of uPA's proteolytic properties and instead is mediated by Rac-regulated profilin expression and cofilin phosphorylation. Our data indicate that binding of uPA to uPAR promotes dendritic spine recovery and improves functional outcome following AIS. PMID:25339736

  11. The urokinase receptor is required for human monocyte chemotaxis in vitro.

    PubMed Central

    Gyetko, M R; Todd, R F; Wilkinson, C C; Sitrin, R G

    1994-01-01

    Mononuclear phagocytes (Mphi) produce urokinase-type plasminogen activator (uPA) and also express a specific cell-surface receptor for urokinase, uPAR. The concomitant expression of these proteins provides a mechanism by which Mphi can degrade extracellular matrix proteins during directed cell migration. In this study, we sought to determine if uPAR plays a role in Mphi chemotaxis that is distinct from its role in matrix proteolysis. Exposing adherent monocytes to a chemotactic gradient causes plasma membrane uPAR to localize strongly to the leading edge of cell migration. Adherence alone or exposure to FMLP had no effect on uPAR expression. Using Boyden chamber chemotaxis assays, we demonstrate that treating mononuclear cells with an anti-uPAR mAb (either as an intact mAb or F[ab']2) ablates chemotaxis induced by FMLP and monocyte chemotactic peptide-1 (P < 0.001). Inactivating the catalytic activity of uPAR-bound uPA had no effect on chemotaxis. Similarly, blocking uPAR expression with an antisense oligonucleotide to uPAR completely ablates chemotaxis, but blocking uPA expression with an antisense oligonucleotide to uPA has a minimal effect. We therefore demonstrate that expression and unimpeded function of uPAR plays an obligate role in M phi chemotaxis by mechanisms that are largely independent of its ligand, uPA. Combined with its known role in mediating pericellular proteolysis, these observations demonstrate that uPAR is essential for both locomotion and traversing tissue barriers during M phi migration. Images PMID:8163642

  12. 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

  13. Arterial insufficiency

    MedlinePlus

    ... is atherosclerosis or "hardening of the arteries." Fatty material (called plaque) builds up on the walls of your arteries. This causes them to become narrow and stiff. As a result, it is hard for blood to flow through your arteries. Blood flow may be suddenly ...

  14. Tissue levels of chemotherapeutic agents for hepatic metastasis during hepatic arterial and portal injection.

    PubMed

    Kaneko, A; Naomoto, Y; Aoyama, M; Tanaka, N

    1999-01-01

    Hepatic metastasis is one of the most important prognostic factors in digestive organ cancer, and hepatic arterial infusion is aggressively performed for therapy of nonresectable metastatic liver cancer. Although comparatively high response rates have been attained in some cases, this treatment has been ineffective in not a few cases because these metastatic tumors are frequently hypovascular in nature. To develop better methods of administering chemotherapeutic agents, we performed basic experiments concerning intraportal administration which has been regarded as having a generally negative effect, focusing on a report indicating that portal supply is dominant along the borders of metastatic liver cancer tumors. VX2 carcinoma cells were inoculated into the hepatic parenchyma beneath the capsule of juvenile Japanese white rabbits. Drugs were infused 2 weeks after the inoculation, then tissue and blood were sequentially sampled. Mitomycin C (1.7 mg/kg) was infused either by bolus injection to the hepatic artery (arterial infusion group) or by bolus injection to the portal vein (portal infusion group). Five-fluorouracil (9.5 mg/kg) and Cisplatin (1.6 mg/kg) were likewise infused continuously over 60 min, and tissue levels of the drugs were compared between the two groups. Mitomycin C and 5-fluorouracil levels were measured by HPLC and Cisplatin levels were measured by atomic absorption spectrophotometry. As a result, the levels of every drug in VX2 tumor tissue did not significantly differ between the arterial infusion group and the portal infusion group, while the levels were significantly higher than those in the intravenous infusion group. Using portal infusion, we observed a drug transition which was not inferior to that of arterial infusion, suggesting that an imported antitumoral effect may be obtained with this method compared with intravenous infusion.

  15. Antibacterial activity of epidural infusions.

    PubMed

    Coghlan, M W; Davies, M J; Hoyt, C; Joyce, L; Kilner, R; Waters, M J

    2009-01-01

    The incidence of epidural abscess following epidural catheterisation appears to be increasing, being recently reported as one in 1000 among surgical patients. This study was designed to investigate the antibacterial activity of various local anaesthetics and additives, used in epidural infusions, against a range of micro-organisms associated with epidural abscess. The aim was to determine which, if any, epidural infusion solution has the greatest antibacterial activity. Bupivacaine, ropivacaine and levobupivacaine crystals were dissolved and added to Mueller-Hinton Agar in concentrations of 0.06%, 0.125%, 0.2%, 0.25%, 0.5% and 1%. Fentanyl, adrenaline and clonidine were also mixed with agar in isolation and in combination with the local anaesthetics. Using a reference agar dilution method, the minimum inhibitory concentrations were determined for a range of bacteria. Bupivacaine showed antibacterial activity against Staphylococcus aureus, Enterococcus faecalis and Escherichia coli with minimum inhibitory concentrations between 0.125% and 0.25%. It did not inhibit the growth of Pseudomonas aeruginosa at any of the concentrations tested. Levobupivacaine and ropivacaine showed no activity against Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa, even at the highest concentrations tested, and minimal activity against Escherichia coli (minimum inhibitory concentrations 0.5% and 1% respectively). The presence of fentanyl, adrenaline and clonidine had no additional effect on the antibacterial activity of any of the local anaesthetic agents. The low concentrations of local anaesthetic usually used in epidural infusions have minimal antibacterial activity. While the clinical implications of this in vitro study are not known, consideration should be given to increasing the concentration of bupivacaine in an epidural infusion or to administering a daily bolus of 0.25% bupivacaine to reduce the risk of epidural bacterial growth.

  16. Evaluation of Ophthalmic Artery Branch Retrograde Intervention in the Treatment of Central Retinal Artery Occlusion (CRAO)

    PubMed Central

    Wang, Runsheng; Qian, Lu; Wang, Yi; Zheng, Yi; Du, Shanshuang; Lei, Tao; Lv, Peilin; Long, Tan; Wang, Wenjun

    2017-01-01

    Background Central retinal artery occlusion (CRAO) is the occlusion of the central retinal artery resulting in retinal infarction and acute vision loss. Digital subtraction angiography (DSA)–guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. This study aimed to evaluate the safety and clinical efficacy of the novel ophthalmic artery branch retrograde thrombolytic intervention for CRAO. Material/Methods Fifty patients with monocular CRAO were enrolled, including 28 males and 22 females (mean age: 55.7±2.3 years). The patients were randomly divided into two groups for thrombolysis with urokinase (400,000 U) and papaverine (30 mg) by either ophthalmic artery branch retrograde intervention (group A, n=26) or superselective ophthalmic artery/selective carotid intervention (group B, n=24). There was no significant difference in age (P=0.58), gender ratio (P=0.49), and time to onset (P=1.00) between the two groups. The adverse reactions and clinical efficacy were evaluated by postoperative DSA, fundus fluorescein angiography (FFA), and visual acuity tests. Results No serious complications, abnormal eye movement, or vitreous hemorrhage occurred in either group. DSA showed that group A had an effective rate (92.30%) comparable to that of group B (100%, χ2=2.08, P=0.25). FFA suggested that both groups had similar treatment efficacy (χ2=3.09, P=0.21). Visual acuity tests also confirmed a similar efficacy of the two intervention approaches (χ2=0.25, P=0.88). Conclusions The developed novel ophthalmic artery branch retrograde intervention is highly effective and safe for CRAO, and may be a superior method compared with the conventional approach. PMID:28064304

  17. Aluminum bioavailability from tea infusion

    PubMed Central

    Yokel, Robert A.; Florence, Rebecca L.

    2008-01-01

    The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer 26Al. 26Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous 27Al infusion. Oral Al bioavailability (F) was calculated from the area under the 26Al, compared to 27Al, serum concentration × time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F = 0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F = 0.1 to 0.3%), but greater than acidic SALP in a biscuit (F = 0.1%). Time to maximum serum 26Al concentration was 1.25, 1.5, 8 and 4.8 h, respectively. These results of oral Al bioavailability × daily consumption by the human suggest tea can provide a significant amount of the Al that reaches systemic circulation. This can allow distribution to its target organs of toxicity, the central nervous, skeletal and hematopoietic systems. Further testing of the hypothesis that Al contributes to Alzheimer's disease may be more warranted with studies focusing on total average daily food intake, including tea and other foods containing appreciable Al, than drinking water. PMID:18848597

  18. Effect of amino acid infusion on the ventilatory response to hypoxia in protein-deprived neonatal piglets.

    PubMed

    Soliz, A; Suguihara, C; Huang, J; Hehre, D; Bancalari, E

    1994-03-01

    Several amino acids (AA) act as neurotransmitters and mediate the ventilatory response to carbon dioxide and hypoxia in adult human beings and animals. To evaluate the influence of AA on the neonatal ventilatory response to hypoxia, 29 newborn piglets less than 5 d old were randomly assigned to a control diet or protein-free diet for 7-10 d. Minute ventilation, arterial blood pressure, oxygen consumption, and arterial blood gases were measured in sedated, spontaneous breathing piglets while they breathed room air and at 1, 5 and 10 min of hypoxia (fraction of inspired oxygen concentration--0.10) before and after 4 h of AA (Trophamine, 3 g/kg, i.v.) or 10% dextrose infusion. The administration of AA solution in protein-deprived piglets resulted in a significant increase in minute ventilation after 10 min of hypoxia (26 +/- 19%) in comparison with their ventilatory response before AA infusion (10 +/- 12%; p < 0.02). Similar increase in the ventilatory response to hypoxia was observed in the control diet group after AA infusion (23 +/- 17% versus 11 +/- 11%; p < 0.05). Changes in arterial blood pressure, oxygen consumption, and arterial blood gases during hypoxia were similar before and after AA infusion. The ventilatory response to hypoxia in both protein-free and control diet animals were similar before and after the 10% dextrose infusion. These results stress the importance of nutritional factors in the neonatal control of breathing.

  19. Infusion of long-chain fatty acid anions by continuous-flow centrifugation

    PubMed Central

    Greenough, William B.; Crespin, Stephen R.; Steinberg, Daniel

    1969-01-01

    We have developed a method for the rapid infusion into plasma of large amounts of long-chain free fatty acids (FFA). Unanesthetized dogs were connected by a peripheral artery to a closed, continuousflow centrifuge from which cells and plasma emerged in separate lines. Sodium oleate was infused directly into the plasma line before cells and plasma were recombined and returned to the animal through a peripheral vein. The centrifugation procedure itself produced only small changes in circulating levels of glucose, FFA, and electrolytes. Plasma flow rates as high as 100 ml/min could be maintained, and centrifugations of 12 hr were accomplished without complications. During centrifugation, sodium oleate was infused at rates up to 80 μEq/kg per min for 2.5 hr; the maximum molar ratio of FFA to albumin without hemolysis was 10:1. Plasma FFA levels rose rapidly after infusions were started and reached constant elevated levels within 15-20 min. Oleate infusion at 10-50 μEq/kg per min produced a rise in plasma FFA proportional to the infusion rate. The maximum increment in plasma FFA above control values was 1.66 μEq/ml. When infusions ended, plasma FFA declined rapidly to control levels. Oleate infusion at rates below 30 μEq/kg per min did not reduce levels of other plasma FFA. Infusion at high rates was accompanied by a marked fall in blood glucose. This method permits adminsitration of long-chain fatty acids in sufficient quantities to study their individual metabolic effects, and provides a new way to supply lipid calories parenterally. PMID:5822596

  20. Immunohistochemical localization of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and α2-antiplasmin in human corneal perforation: a case report

    PubMed Central

    2012-01-01

    Background Corneal ulceration leading to perforation is associated with infectious and non-infectious destructive conditions in the cornea. The fibrinolytic (plasminogen/plasmin) system is considered to contribute to tissue remodeling in the wound healing process and it is believed to play an important role in proteolysis and fibrosis. To determine the localization of urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR) and α2-antiplasmin (α2AP) in the tissue of a corneal perforation, we investigated immunohistochemical expressions of u-PA, u-PAR, α2AP, CD68, and α-smooth muscle actin (α-SMA) in a patient with corneal perforation that developed from an ulcer of no clear cause. Case presentation The patient was a 77-year-old woman who presented with a perforated corneal ulcer in her right eye. The cause of her corneal ulcer was unknown. Double immunohistochemistry was performed for the combinations of u-PA with u-PAR, CD68 or α-SMA and α2AP with CD68 or α-SMA to detect the localization of u-PA and α2AP. u-PA and u-PAR co-localization was seen in the corneal ulceration area. u-PA was mainly observed in CD68-positive cells and in some α-SMA positive cells. On the other hand, α2AP was not expressed in CD68-positive cells, but was expressed in α-SMA positive cells. Conclusion We identified expression of the u-PA/u-PAR complex and α2AP in a patient with a corneal ulcer. These two molecules are believed to play a crucial role in inflammatory cell recruitment, ECM synthesis and degradation during corneal wound healing. PMID:23190581

  1. Drug Infusion Systems: Technologies, Performance, and Pitfalls.

    PubMed

    Kim, Uoo R; Peterfreund, Robert A; Lovich, Mark A

    2017-02-16

    This review aims to broadly describe drug infusion technologies and raise subtle but important issues arising from infusion therapy that can potentially lead to patient instability and morbidity. Advantages and disadvantages of gravity-dependent drug infusion are described and compared with electromechanical approaches for precise control of medication infusion, including large-volume peristaltic and syringe pumps. This review discusses how drugs and inert carriers interact within infusion systems and outlines several complexities and potential sources of drug error. Major topics are (1) the importance of the infusion system dead volume; (2) the quantities of coadministered fluid and the concept of microinfusion; and (3) future directions for drug infusion.The infusion system dead volume resides between the point where drug and inert carrier streams meet and the patient's blood. The dead volume is an often forgotten reservoir of drugs, especially when infusion flows slow or stop. Even with medications and carriers flowing, some mass of drug always resides within the dead volume. This reservoir of drug can be accidentally delivered into patients. When dose rate is changed, there can be a significant lag between intended and actual drug delivery. When a drug infusion is discontinued, drug delivery continues until the dead volume is fully cleared of residual drug by the carrier. When multiple drug infusions flow together, a change in any drug flow rate transiently affects the rate of delivery of all the others. For all of these reasons, the use of drug infusion systems with smaller dead volumes may be advantageous.For critically ill patients requiring multiple infusions, the obligate amount of administered fluid can contribute to volume overload. Recognition of the risk of overload has given rise to microinfusion strategies wherein drug solutions are highly concentrated and infused at low rates. However, potential risks associated with the dead volume may be magnified

  2. 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. ...

  3. Steady States and Dynamics of Urokinase-Mediated Plasmin Activation In Silico and In Vitro

    PubMed Central

    Venkatraman, Lakshmi; Li, Huipeng; Dewey, C. Forbes; White, Jacob K.; Bhowmick, Sourav S.; Yu, Hanry; Tucker-Kellogg, Lisa

    2011-01-01

    Plasmin (PLS) and urokinase-type plasminogen activator (UPA) are ubiquitous proteases that regulate the extracellular environment. Although they are secreted in inactive forms, they can activate each other through proteolytic cleavage. This mutual interplay creates the potential for complex dynamics, which we investigated using mathematical modeling and in vitro experiments. We constructed ordinary differential equations to model the conversion of precursor plasminogen into active PLS, and precursor urokinase (scUPA) into active urokinase (tcUPA). Although neither PLS nor UPA exhibits allosteric cooperativity, modeling showed that cooperativity occurred at the system level because of substrate competition. Computational simulations and bifurcation analysis predicted that the system would be bistable over a range of parameters for cooperativity and positive feedback. Cell-free experiments with recombinant proteins tested key predictions of the model. PLS activation in response to scUPA stimulus was found to be cooperative in vitro. Finally, bistability was demonstrated in vitro by the presence of two significantly different steady-state levels of PLS activation for the same levels of stimulus. We conclude that ultrasensitive, bistable activation of UPA-PLS is possible in the presence of substrate competition. An ultrasensitive threshold for activation of PLS and UPA would have ramifications for normal and disease processes, including angiogenesis, metastasis, wound healing, and fibrosis. PMID:22004735

  4. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    SciTech Connect

    Takahashi, K.; Gojobori, T.; Tanifuji, M. )

    1991-02-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate.

  5. Effects of abomasal vegetable oil infusion on splanchnic nutrient metabolism in lactating dairy cows.

    PubMed

    Benson, J A; Reynolds, C K; Aikman, P C; Lupoli, B; Beever, D E

    2002-07-01

    Changes in the metabolism of nutrients by the portal-drained viscera (PDV) and liver may contribute to the reduction in dry matter intake (DMI) and other production responses generally observed in lactating dairy cows fed supplemental long-chain fatty acids (LCFA). In the present study, effects of a 7-d abomasal infusion of vegetable oil on arterial concentration and splanchnic (PDV and liver) metabolism of nutrients were measured in six cows at 55 (early lactation [ELAC]) and 111 (midlactation [MLAC]) d postpartum. Cows were fed for ad libitum DMI at 8-h intervals, and blood samples for measurement of splanchnic metabolism were obtained over 8 h beginning 2 h before feeding at 0830 h. Blood flow for the PDV and liver was increased by oil infusion and was greater in ELAC, despite similar-feed DMI during blood sampling. Increased blood flow in ELAC was associated with greater liver oxygen removal and glucose release that accompanied greater milk yield. In contrast, oil infusion had no effect on splanchnic oxygen use. Greater blood flow during oil infusion may have been due to specific effects of intestinal LCFA supply on PDV blood flow. Net PDV release and liver removal of branched-chain volatile fatty acids (VFA) and ammonia were increased by oil infusion. Net PDV release of longer-chain (4 and 5 C) VFA and NEFA was greater in ELAC, but net PDV flux of other nutrients was not affected by lactation stage, possibly due to the similarity of feed DMI. Oil infusion increased arterial concentration and net PDV release and liver removal of NEFA, and it decreased net liver release and arterial concentration of glucose. Effects of oil infusion on liver glucose release were associated with decreased daily DMI. In ELAC, arterial concentration and net liver removal of NEFA were also increased, but liver release of glucose was greater than in MLAC. Oil infusion and ELAC both increased net liver removal of L-lactate. The resulting decrease in net total splanchnic release of L

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

    PubMed

    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

    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). We measured the plasma suPAR levels in 138 patients with IgAN, and then their clinical and pathological relationships were analyzed. 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. 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.

  7. Acute propranolol infusion stimulates protein synthesis in rabbit skin wound.

    PubMed

    Zhang, Xiao-Jun; Meng, Chengyue; Chinkes, David L; Finnerty, Celeste C; Aarsland, Asle; Jeschke, Marc G; Herndon, David N

    2009-05-01

    Propranolol administration has been demonstrated to improve cardiac work, decrease energy expenditure, and attenuate lipolysis in burned patients; however, its effect on wound healing has not been reported. In rabbits, a partial-thickness skin donor site wound was created on the back, and catheters were placed in the carotid artery and jugular vein. A nasogastric feeding tube was placed for enteral feeding. On day 5 after injury, stable isotope tracers were infused to determine protein and DNA kinetics in the wound. Propranolol hydrochloride was injected in 1 group during the tracer infusion to decrease heart rate, and the other group without propranolol injection served as a control. The propranolol infusion decreased heart rate by 21%. The protein fractional synthetic rate in the wound was greater in the propranolol group (8.6 +/- 0.9 vs 6.1 +/- 0.5%/day, P < .05). Wound protein fractional breakdown rates were not significantly different. The rate of protein deposition (synthesis - breakdown) was increased in the propranolol group (5.0 +/- 1.2 vs 2.8 +/- 0.7%/day, P = .07). Wound DNA fractional synthetic rates were comparable. The protein fractional synthetic rate was correlated with percent decrease in heart rate, but expression of the beta-adrenergic receptors and downstream signaling cascades in local wounds were not affected after propranolol treatment. Propranolol infusion increased wound protein synthetic rate and tended to increase wound protein deposition rate, which might be beneficial to wound healing. These changes might reflect a systemic response to the beta-adrenergic blockade.

  8. Effect of mesenteric vein infusion of propionate on splanchnic metabolism in primiparous Holstein cows.

    PubMed

    Casse, E A; Rulquin, H; Huntington, G B

    1994-11-01

    Our objective was to assess the effects of increased propionate supply on gut and liver function in lactating cows. Four multicatheterized, primiparous cows (30.4 +/- .5 kg/d of milk) were fed for ad libitum intake a diet of 50% alfalfa hay and 50% concentrate (20.6 +/- 1.9 kg/d of DM, 226 +/- 21 MJ/d of metabolizable energy, and 611 +/- 56 g/d of N). Each cow received intramesenteric infusions of NaCl (control) or Na-propionate (150 mmol/h of a 2.5 M solution) in a reversal design. After 72 h of infusion, blood flow (by indicator dilution) and net flux (venoarterial differences multiplied by blood flow) were measured across portal-drained viscera and the liver. Energy supply from feed consumed and from infusion was similar between treatments. Energy that was excreted as milk decreased with propionate infusion. Propionate infusion increased arterial concentration of propionate; decreased absorption of acetate, butyrate, and valerate; and decreased hepatic removal of L-lactate, butyrate, valerate, NEFA, and oxygen. Propionate infusion decreased splanchnic release of glucose and increased splanchnic release of acetate and alanine. Net flux of urea, BHBA, insulin, or glucagon was unaffected by treatments. Our data show a link between a greater proportion of energy supplied as propionate and decreased energy excreted as milk. This response was associated with decreased net removal of glucogenic and ketogenic substrates by the liver and increased supply of acetate for use by peripheral tissues.

  9. 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.

  10. Use of three infusion pumps for postoperative administration of buprenorphine or morphine in dogs.

    PubMed

    Gilberto, David B; Motzel, Sherri L; Bone, Ashleigh N; Burns, Carol L; Zeoli, Angela H; Lodge, Kenneth E; Goode, Tamara L

    2002-06-01

    Results of using an implantable osmotic pump, a preset disposable infusion pump, or a reusable programmable infusion pump for postoperative administration of buprenorphine or morphine in dogs undergoing abdominal surgery are described. Ten dogs underwent abdominal surgery for implantation of vascular access ports. Dogs were given buprenorphine s.c. by use of an implantable osmotic pump (4 dogs), morphine s.c. by use of a preset infusion pump (4), or buprenorphine intra-arterially by use of a programmable infusion pump (2). Dogs were monitored, and serum buprenorphine or morphine concentration was measured for 72 hours after surgery; pumps were removed 48 hours after surgery. Severity of pain was determined by assigning a pain score. The preset infusion pump and the programmable infusion pump resulted in comparable pain relief and sustained serum analgesic concentrations throughout the recovery period. However, the cost of the pumps and other associated factors may limit their use to dogs undergoing invasive surgical procedures expected to result in substantial postoperative pain. The level of analgesia obtained with the implantable osmotic pumps was inconsistent.

  11. Cardiovascular Effects of Dobutamine and Phenylephrine Infusion in Sevoflurane-anesthetized Thoroughbred Horses

    PubMed Central

    OHTA, Minoru; KURIMOTO, Shinjiro; ISHIKAWA, Yuhiro; TOKUSHIGE, Hirotaka; MAE, Naomi; NAGATA, Shun-ichi; MAMADA, Masayuki

    2013-01-01

    ABSTRACT 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. Synergic Effects of Rehabilitation and Intravenous Infusion of Mesenchymal Stem Cells After Stroke in Rats.

    PubMed

    Sasaki, Yuichi; Sasaki, Masanori; Kataoka-Sasaki, Yuko; Nakazaki, Masahito; Nagahama, Hiroshi; Suzuki, Junpei; Tateyama, Daiki; Oka, Shinichi; Namioka, Takahiro; Namioka, Ai; Onodera, Rie; Mikami, Takeshi; Wanibuchi, Masahiko; Kakizawa, Masafumi; Ishiai, Sumio; Kocsis, Jeffery D; Honmou, Osamu

    2016-11-01

    Intravenous infusion of mesenchymal stem cells (MSCs) derived from adult bone marrow improves behavioral function in rat stroke models. Rehabilitation therapy through physical exercise also provides therapeutic efficacy for cerebral ischemia. The purpose of this study was to investigate whether synergic effects of daily rehabilitation and intravenous infusion of MSCs has therapeutic effects after stroke in rats. This was an experimental study. A permanent middle cerebral artery occlusion (MCAO) was induced by intraluminal vascular occlusion with a microfilament. Four experimental groups were studied: group 1 (vehicle only, n=10), group 2 (vehicle + exercise, n=10), group 3 (MSCs only, n=10), and group 4 (MSCs + exercise, n=10). Rat MSCs were intravenously infused at 6 hours after MCAO, and the rats received daily rehabilitation with treadmill running exercise for 20 minutes. Lesion size was assessed at 1, 14, and 35 days using magnetic resonance imaging. Functional outcome was assessed using the Limb Placement Test. Both combined therapy and MSC infusion reduced lesion volume, induced synaptogenesis, and elicited functional improvement compared with the groups without MSC infusion, but the effect was greater in the combined therapy group. A limitation of this study is that the results were limited to an animal model and cannot be generalized to humans. The data indicate that the combined therapy of daily rehabilitation and intravenous infusion of MSCs improved functional outcome in a rat MCAO model. © 2016 American Physical Therapy Association.

  13. 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

  14. Microcirculatory Response In Vivo on Local Intraarterial Infusion of Autogenic Adipose-derived Stem Cells or Stromal Vascular Fraction

    PubMed Central

    2016-01-01

    Background: Both adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) have been demonstrated to have regenerative properties with therapeutic potential for numerous diseases through local or topical applications. However, it is unclear whether ASC or SVF can be delivered systemically through an intra-arterial infusion. The purpose of this study was to examine the microcirculatory response in vivo on local intraarterial infusion of autogenic ASCs or SVF in a vascular pedicle isolated rat cremaster microcirculation model. Materials and Methods: Fat tissue was surgically harvested from the flanks of male Sprague–Dawley rats (n = 12) and processed for SVF isolation. Some SVF samples were cultured for 24 hours for ASC purification. The autogenic SVF (1 × 105) cells (n = 6) or purified ASC (1 × 105) cells (n = 6) cells were infused into the microcirculation of cremaster muscle at a speed of 0.05 mL/min through the cannulation of femoral artery. As this is a vascular pedicle isolated preparation, the infused SVF or ASC cells went nowhere but the cremaster muscle. The video image of the microcirculation was monitored in real time during infusion. Results: Arteriole diameter was measured as A1 (100–160 µm), A2 (40–80 µm), and A3/A4 (10–30 µm). Capillary perfusion was quantified in 18 capillary fields of each muscle. There was a significant increase in the diameter of terminal arterioles (P = 0.049) and the capillary density (P = 0.02) after ASC intraarterial infusion. However, a significant cell aggregation, embolisms, and arterial obstruction were observed in the microcirculation in every case during SVF infusion. Conclusions: Intraarterial infusion is an appropriate route for the delivery of autogenic ASCs, but not of SVF. SVF-induced microembolisms were the reason for narrowing or blocking the lumen of terminal arterioles, resulting in no flow in the corresponding capillaries. PMID:27757364

  15. Delivery of a novel nitrosourea, MCNU, to the brain tissue in glioma-bearing rats. Intracarotid versus intravenous infusion.

    PubMed

    Hodozuka, A; Sako, K; Nakai, H; Tomabechi, M; Suzuki, N; Yonemasu, Y

    1993-01-01

    We observed the tissue delivery of a novel water-soluble nitrosourea, 1-(2-chloroethyl)-3-(methyl-alpha-D-glucopyranos-6-yl)-1-nitros our ea (MCNU) in rats bearing experimental brain tumors by conducting autoradiography on all. Prior to this study, the development of a streaming phenomenon was ascertained (and thus finding the optimum velocity for intra-arterial infusion) by 14C-iodoantipyrine (IAP) autoradiography. Furthermore, a single pass extraction value of MCNU was measured. At an arterial infusion rate of 0.2 ml/min., the streaming phenomenon was recognized but the tracer was fairly evenly distributed at a rate of 1.0 ml/min. On the other hand, the single pass extraction value for MCNU was 0.18 +/- 0.036 (mean +/- S.D., n = 3, under pentobarbital anesthesia). It was suggested that MCNU is very unlikely to be transported into the normal rat brain. We conducted 14C-MCNU autoradiography to observe tissue distribution of MCNU following its intra-arterial and intravenous infusions in a brain tumor model using rats. The normal side (the side where no infusions were given) and the cerebral cortex at the side affected by the tumor (the side where the infusion was given) showed hardly any uptake of 14C-MCNU in both the intra-arterial and intravenous infusion groups. The tumorous section was divided into the periphery and the center to measure tissue concentration of the tracer in each section. Compared against the cortical section, the periphery and the center showed significant increases in the concentration (approximately 11 to 15 times and 3 to 7 times, respectively, the figure for the cortical region) for both the intra-arterial and intravenous groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. 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.

  17. Continuous infusion indicator dilution measurement of limb blood flow and vascular response to magnesium sulfate in normotensive and hypertensive men

    PubMed Central

    Overbeck, Henry W.; Daugherty, Robert M.; Haddy, Francis J.

    1969-01-01

    A constant infusion, indicator dilution technique for blood flow measurements in the forearm and hand of man was tested and validated in vitro and in vivo. This technique employs jet injection to improve mixing of indicator with arterial blood. The mixing characteristics of the jet injection system were studied in vitro in tubing simulating the brachial artery of man. In addition, actual blood flows in the isolated pump-perfused forelimbs of five dogs were compared with constant infusion, indicator dilution calculated flows. Measurements were also made of mixing and of blood flow in the forearm and hand of man. The technique was used to compare forearm and hand vascular responses with constant intrabrachial arterial infusions of magnesium sulfate in 13 normotensive and 13 essential hypertensive men. In vitro and in vivo the jet injection system significantly improved mixing of indicator with blood, as compared with mixing produced by standard infusion techniques, without causing hemolysis. In 30 measurements in isolated, perfused dog forelimbs the correlation coefficient between actual and calculated blood flow was 0.992. Resting limb vascular resistance in the hypertensive group was significantly higher than in the normotensive group. Limb vascular resistance in all 26 men decreased in response to intrabrachial-arterial infusion of 0.25% magnesium sulfate (8 ml/min). Rate of infusion of Mg++ was 0.162 mEq/min. There was a significant positive linear correlation between level of initial limb vascular resistance and magnitude of response to magnesium sulfate. Vascular response data adjusted for this source of variation were similar in hypertensives and normotensives. The data suggest that this constant infusion, indicator dilution technique allows accurate calculation of total limb blood flow in man, provided that anomalous bifurcation of the brachial artery is not present. The data also suggest that the jet injection system improves mixing of substances with

  18. Enhanced Distal Nephron Sodium Reabsorption in Chronic Angiotensin II Infused Mice

    PubMed Central

    Zhao, Di; Seth, Dale M.; Navar, L. Gabriel

    2009-01-01

    Chronic angiotensin II (Ang II) infusions enhance urinary excretion of angiotensinogen suggesting augmentation of distal nephron sodium reabsorption. To assess if chronic Ang II infusions (15 ng/min for 2 weeks) enhance distal nephron sodium reabsorption, we compared sodium excretion before and following blockade of the two main distal nephron sodium transporters by iv amiloride (5 mg/kg body weight) plus bendroflumethiazide (12 mg/kg body weight) in male C57/BL6 anesthetized control mice (n=10) and in chronic Ang II-infused mice (n=8). Chronic Ang II infusions increased systolic blood pressure to 141±6 mm Hg compared to 106±4 mm Hg in control mice. After anesthesia, mean arterial pressure averaged 97±4 mm Hg in chronic Ang II-infused mice compared with 94±3 mm Hg in control mice allowing comparison of renal function at similar arterial pressures. Ang II-infused mice had lower urinary sodium excretion (0.16±0.04 versus 0.30±0.05 μEq/min, P<0.05), higher distal sodium reabsorption (1.74±0.18 versus 1.12±0.18 μEq/min, P<0.05) and higher fractional reabsorption of distal sodium delivery (91.1±1.8% versus 77.9±4.3 %, P<0.05) than control mice. Urinary Ang II concentrations, measured during distal blockade, were greater in Ang II infused mice (1235.0±277.2 versus 468.9±146.9 fmol/ml, P<0.05). In chronic Ang II-infused mice treated with spironolactone (n=5), fractional reabsorption of distal sodium delivery was similarly augmented as in chronic Ang II infused mice (94.6±1.7%, P<0.01). These data provide in vivo evidence that there is enhanced distal sodium reabsorption dependent on sodium channel and Na+-Cl− cotransporter activity and increased urinary Ang II concentrations in mice infused chronically with Ang II. PMID:19487583

  19. 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

  20. 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%.

  1. Brachioradial arteries with anastomotic arteries connecting to brachial arteries bilaterally.

    PubMed

    Hong, Tong; Qiuhong, Dan; Haipeng, Cai

    2010-01-01

    We present a patient with a failed radial coronary angioplasty as a result of bilateral brachioradial arteries, the radial arteries anomalously originating from the axillary arteries. We review the literature concerning abnormal origins of the radial artery and propose the left ulnar artery as optimal access of choice in cases with a right brachioradial artery of relatively small size in its proximal part.

  2. [The effect of hypoxia on the urokinase and adenylate cyclase systems in the culture of endothelial cells of the human umbilical vein].

    PubMed

    Kapustin, A N; Tishchenko, E P; Torosian, N A; Panina, O B; Tsokolaeva, Z I; Ratner, E I; Savel'eva, G M; Parfenova, E V

    2005-06-01

    Hypoxia induces angiogenesis in ischemized tissues by means of pro-angiogenic factor expression. The key role in the growth processes and blood vessel functioning belongs to the matrix metalloproteinases, plasminogen, and its activator systems. Effect of hypoxia on expression of the urokinase activating agent plasminogen and its receptor in endothelium was studied in human umbilical vein endothelial cell model. Incubation of the endothelial cells under the conditions of hypoxia proved to reduce both urokinase formation in these cells and its secreting into the culture medium. The hypoxia-induced reduction of urokinase contents was accompanied by enhancement of expression of the urokinase receptor. The hypoxia also entailed reduction of the adenylate cyclase activity and cAMP contents in the endothelial cells. The data obtained suggest that reduction of the adenylate cyclase activity and cAMP contents under the conditions of hypoxia provide basis for suppression of the urokinase expression by the endothelial cells and, consequently, inhibition of blood vessel formation in the ischemized tissue.

  3. Safety of Infusing Ipilimumab Over 30 Minutes

    PubMed Central

    Momtaz, Parisa; Park, Vivian; Panageas, Katherine S.; Postow, Michael A.; Callahan, Margaret; Wolchok, Jedd D.; Chapman, Paul B.

    2015-01-01

    Purpose The approved dose of ipilimumab is 3 mg/kg infused over 90 minutes; however, in clinical trials, 10 mg/kg has also been infused over 90 minutes. At this higher dose, patients receive 3 mg/kg within the first 27 minutes of treatment. We sought to determine whether the standard dose of 3 mg/kg could be safely infused over 30 minutes. Methods We reviewed retrospectively the incidence of infusion-related reactions (IRRs) to ipilimumab at our institution in patients receiving doses of either 3 or 10 mg/kg infused over 90 minutes. Our findings led to a change in institutional guidelines for ipilimumab infusion time from 90 minutes to 30 minutes. We reviewed the first 14 months of our prospective experience using a 30-minute infusion of ipilimumab. Results Between April 1, 2008, and June 30, 2013, 595 patients received 2,507 doses of ipilimumab infused at either 3 mg/kg (n = 457) or 10 mg/kg (n = 138) over 90 minutes. Although the 10 mg/kg group had a higher incidence of IRRs (4.3%) than the 3 mg/kg group (2.2%), this difference was not statistically significant (P = .22). In 120 patients treated prospectively with ipilimumab 3 mg/kg infused over 30 minutes, seven patients (5.8%) had an IRR (P = .06 compared with 90-minute infusions). All IRRs occurred at dose 2; six were grade 2, and one was grade 3. All seven patients received subsequent doses of ipilimumab safely, the majority with premedication. Conclusion Ipilimumab at 3 mg/kg can be infused safely over 30 minutes with an acceptably low incidence of IRRs. After an IRR, patients can safely receive additional doses of ipilimumab with premedication. PMID:26124475

  4. Arterial calcifications

    PubMed Central

    Rennenberg, Roger J M W; Schurgers, Leon J; Kroon, Abraham A; Stehouwer, Coen D A

    2010-01-01

    Abstract Arterial calcifications as found with various imaging techniques, like plain X-ray, computed tomography or ultrasound are associated with increased cardiovascular risk. The prevalence of arterial calcification increases with age and is stimulated by several common cardiovascular risk factors. In this review, the clinical importance of arterial calcification and the currently known proteins involved are discussed. Arterial calcification is the result of a complex interplay between stimulating (bone morphogenetic protein type 2 [BMP-2], RANKL) and inhibitory (matrix Gla protein, BMP-7, osteoprotegerin, fetuin-A, osteopontin) proteins. Vascular calcification is especially prevalent and related to adverse outcome in patients with renal insufficiency and diabetes mellitus. We address the special circumstances and mechanisms in these patient groups. Treatment and prevention of arterial calcification is possible by the use of specific drugs. However, it remains to be proven that reduction of vascular calcification in itself leads to a reduced cardiovascular risk. PMID:20716128

  5. Urokinase-type plasminogen activator: a new target for male contraception?

    PubMed Central

    Qin, Ying; Han, Yan; Xiong, Cheng-Liang; Li, Hong-Gang; Hu, Lian; Zhang, Ling

    2015-01-01

    Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P < 0.05) when compared with control groups. However, the mating capacity and reproductive organ weights had no obvious change, and histological analysis of the testes and epididymides also showed normal morphology for immunized male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P < 0.05). Together, these observations indicated that subcutaneous injection human uPA to the male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development. PMID:25578931

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

    PubMed

    Patecki, Margret; von Schaewen, Markus; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika

    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.

  7. Computer-assisted mutagenesis of ecotin to engineer its secondary binding site for urokinase inhibition.

    PubMed

    Laboissière, Martha C A; Young, Malin M; Pinho, Rilva G; Todd, Stephen; Fletterick, Robert J; Kuntz, Irwin; Craik, Charles S

    2002-07-19

    Inhibitors of urokinase-type plasminogen activator (uPA) were selected in vitro from two ecotin phage-display libraries to study the effect on binding of amino acid substitutions at critical positions 108, 110, 112, and 113 within the 100s loop (RNKL, respectively, in wild type ecotin). The first, a focused library, was the result of a computation-assisted approach using the three-dimensional structure of the ecotin-trypsin complex to guide the modeling of amino acid substitutions predicted to increase affinity for uPA. The second, a complete library, allowed for all substitutions at the above identified positions. The consensus sequences selected from the focused, and complete libraries were RRWS and R(R/N)QL, respectively. Inhibition constant determinations showed ecotin variants containing these sequences to be similarly potent (K(i) = 1-2 nm). These substitutions were combined with previously identified substitutions in another critical region of ecotin. One of these combinations (D70R/M84R/RRQL) is the tightest (K(i) = 50 pm) ecotin variant inhibitor of uPA. The blending of combinatorial methods and computer algorithms designed to predict stronger binders has allowed us to obtain protein derivatives that exhibit greatly increased affinity for a predetermined target. This technology can be applied to select for enhanced binding interactions at protein-protein interfaces and accelerate the process of protease inhibitor development.

  8. The structure of the urokinase-type plasminogen activator receptor gene.

    PubMed

    Casey, J R; Petranka, J G; Kottra, J; Fleenor, D E; Rosse, W F

    1994-08-15

    The cellular receptor for urokinase-type plasminogen activator (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that plays a central role in pericellular plasminogen activation. It contains 313 amino acid residues, including 28 cysteine residues in a pattern of three homologous repeats. The cysteine residue pattern suggests that uPAR belongs to a superfamily of proteins including CD59, murine Ly-6, and a variety of elapid snake venom toxins. A novel 1.7-kb uPAR cDNA was isolated that is missing exon 5 and that contains 380 bp not previously reported at the 5' end. This cDNA was used to probe a human genomic library from which three clones were isolated and analyzed. The uPAR gene consists of 7 exons spread over 23 kb of genomic DNA. Exons 2, 4, and 6 code for homologous domains within the mature protein, as do exons 3, 5, and 7; CD59-like homologous pairs are encoded by exons 2-3, 4-5, and 6-7, respectively. The structure of the gene for uPAR further confirms the relationship of this molecule to the superfamily containing CD59, Ly-6, and the elapid snake venom toxins.

  9. Elevation of serum urokinase plasminogen activator receptor and liver stiffness in postoperative biliary atresia

    PubMed Central

    Udomsinprasert, Wanvisa; Honsawek, Sittisak; Jirathanathornnukul, Napaphat; Chongsrisawat, Voranush; Poovorawan, Yong

    2016-01-01

    AIM To investigate serum urokinase-type plasminogen activator receptor (uPAR) and liver stiffness in biliary atresia (BA) and examine the correlation of circulating uPAR, liver stiffness, and clinical outcomes in postoperative BA children. METHODS Eighty-five postKasai BA children and 24 control subjects were registered. Circulating uPAR was measured using enzyme-linked immunosorbent essay. Liver stiffness was analyzed using transient elastography. RESULTS BA children had significantly greater circulating uPAR and liver stiffness scores than control subjects (P < 0.001). Circulating uPAR and liver stiffness were substantially higher in jaundiced BA children than non-jaundiced BA children (P < 0.001). In addition, circulating uPAR was positively associated with serum aspartate aminotransferase (r = 0.507, P < 0.001), alanine aminotransferase (r = 0.364, P < 0.001), total bilirubin (r = 0.559, P < 0.001), alkaline phosphatase (r = 0.325, P < 0.001), and liver stiffness scores (r = 0.508, P < 0.001). CONCLUSION Circulating uPAR and liver stiffness values were greater in BA children than healthy controls. The increased circulating uPAR was associated with liver dysfunction in BA. As a consequence, serum uPAR and liver stiffness may be used as noninvasive biomarkers indicating the progression of liver fibrosis in postKasai BA. PMID:27957246

  10. Pyelonephritis: renal urokinase activity in rats on essential fatty acid diets.

    PubMed

    du Toit, P J; van Aswegen, C H; Nel, J D; Strasheim, B; Becker, P J; du Plessis, D J

    1994-01-01

    This study was undertaken to assess whether additions of different oils to the diets of male rats would affect the renal urokinase (UK) activity of healthy and pyelonephritic kidneys. Four groups of fatty acid diets were studied: fat-free, coconut oil, fish oil and evening primrose oil (EPO). Pyelonephritis was obtained by unilateral extrarenal urinary obstruction and subcutaneous injection of Escherichia coli. The UK activity of the non-obstructed kidneys did not differ statistically between rats infected and not infected with bacteria (P > 0.056), except within the coconut oil group. A statistically decreased UK activity was obtained with bacteria injected animals on a coconut oil diet (P < 0.0001). This phenomenon, namely a decrease in UK activity, was also seen with pyelonephritic kidneys of rats on fat-free, coconut and fish oil diets (P < 0.0065). However, the UK activity of the obstructed kidneys with and without infection in the EPO group remained similar (P = 0.8477). These results suggest that the UK activity in infection-induced renal stones may be restored by EPO containing diets and may be of high relevance in the prevention and treatment of infection-induced renal stones. This revelation now needs to be more fully investigated.

  11. Differential expression of the urokinase receptor (CD87) in arthritic and normal synovial tissues.

    PubMed Central

    Szekanecz, Z; Haines, G K; Koch, A E

    1997-01-01

    AIM: To determine whether the urokinase plasminogen activator receptor (u-PAR; CD87) exhibits a possible pathogenic role in rheumatoid and osteoarthritis. METHODS: A semiquantitative, indirect immunoperoxidase histochemical analysis was performed on frozen synovial tissue sections. The recently characterised monoclonal antibody 10G7 recognising transfectants bearing u-PAR was used. Synovial tissue was obtained from 10 patients with rheumatoid arthritis, 10 patients with osteoarthritis, and four normal subjects. RESULTS: u-PAR was expressed on 70-90% of synovial tissue lining cells and subsynovial, interstitial macrophages from the arthritis patients, but only on a few myeloid cells from the normal subjects. It was also present on more endothelial cells from the rheumatoid and osteoarthritis patients, than from normal synovial tissue. CONCLUSIONS: Plasminogen activators are important in joint destruction underlying arthritis. The up-regulated expression of u-PAR in diseased versus normal synovial tissue suggests a role for this antigen in the inflammatory and angiogenic mechanisms underlying rheumatoid and osteoarthritis. Images PMID:9215148

  12. Involvement of urokinase-type plasminogen activator system in cancer: an overview.

    PubMed

    Mekkawy, Ahmed H; Pourgholami, Mohammad H; Morris, David L

    2014-09-01

    Currently, there are several studies supporting the role of urokinase-type plasminogen activator (uPA) system in cancer. The association of uPA to its receptor triggers the conversion of plasminogen into plasmin. This process is regulated by the uPA inhibitors (PAI-1 and PAI-2). Plasmin promotes degradation of basement membrane and extracellular matrix (ECM) components as well as activation of ECM latent matrix metalloproteases. Degradation and remodeling of the surrounding tissues is crucial in the early steps of tumor progression by facilitating expansion of the tumor mass, release of tumor growth factors, activation of cytokines as well as induction of tumor cell proliferation, migration, and invasion. Hence, many tumors showed a correlation between uPA system component levels and tumor aggressiveness and survival. Therefore, this review summarizes the structure of the uPA system, its contribution to cancer progression, and the clinical relevance of uPA family members in cancer diagnosis. In addition, the review evaluates the significance of uPA system in the development of cancer-targeted therapies.

  13. Retro-inverso Urokinase Receptor Antagonists for the Treatment of Metastatic Sarcomas.

    PubMed

    Carriero, Maria Vincenza; Bifulco, Katia; Ingangi, Vincenzo; Costantini, Susan; Botti, Giovanni; Ragone, Concetta; Minopoli, Michele; Motti, Maria Letizia; Rea, Domenica; Scognamiglio, Giosuè; Botti, Gerardo; Arra, Claudio; Ciliberto, Gennaro; Pessi, Antonello

    2017-05-02

    The development of metastases is a multistep process that requires the activation of physiological and biochemical processes that govern migration, invasion and entry of metastatic cells into blood vessels. The urokinase receptor (uPAR) promotes cell migration by interacting with the Formyl Peptide Receptors (FPRs). Since both uPAR and FPR1 are involved in tumor progression, the uPAR-FPR1 interaction is an attractive therapeutic target. We previously described peptide antagonists of the uPAR-FPR1 interaction that inhibited cell migration and angiogenesis. To develop enzyme-resistant analogues, we applied here the Retro-Inverso (RI) approach, whereby the topology of the side chains is maintained by inverting the sequence of the peptide and the chirality of all residues. Molecular dynamics suggests that peptide RI-3 adopts the turn structure typical of uPAR-FPR1 antagonists. Accordingly, RI-3 is a nanomolar competitor of N-formyl-Met-Leu-Phe for binding to FPR1 and inhibits migration, invasion, trans-endothelial migration of sarcoma cells and VEGF-triggered endothelial tube formation. When sarcoma cells were subcutaneously injected in nude mice, tumor size, intra-tumoral microvessel density, circulating tumor cells and pulmonary metastases were significantly reduced in animals treated daily with 6 mg/Kg RI-3 as compared to animals treated with vehicle only. Thus, RI-3 represents a promising lead for anti-metastatic drugs.

  14. Inhibition of tumor growth and metastasis by ATF-Fc, an engineered antibody targeting urokinase receptor.

    PubMed

    Hu, Xian-Wen; Duan, Hai-Feng; Gao, Li-Hua; Pan, Shu-Yuan; Li, Yong-Mei; Xi, Yongyi; Zhao, Su-Rong; Yin, Liang; Li, Jin-Feng; Chen, Hui-Peng; Wu, Chu-Tse

    2008-05-01

    Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. In this study, ATF-Fc, an antibody-like molecule comprising the amino-terminal fragment of human uPA (ATF) linked to the Fc fragment of human IgG1 via a flexible linker was developed. Its antitumor activities were evaluated in vitro and in vivo. The results showed that ATF-Fc had obvious cytotoxic effect on several types of tumor cells, which is dependent on cellular expression of uPAR and its Fc fragment. Treatment with ATF-Fc caused a significant suppression on tumor growth and metastasis of xenograft human tumors (MCF-7 breast cancer and BGC-823 gastric cancer) in athymic nude mice. Furthermore, we demonstrated that ATF-Fc had an anti-angiogenesis activity both in vitro and in vivo. In conclusion, we provided a novel therapeutic antibody-like molecule in the management of a variety of solid tumors by disrupting the uPA/uPAR interaction.

  15. Urokinase Receptor Promotes Skin Tumor Formation by Preventing Epithelial Cell Activation of Notch1.

    PubMed

    Mazzieri, Roberta; Pietrogrande, Giovanni; Gerasi, Laura; Gandelli, Alessandro; Colombo, Piergiuseppe; Moi, Davide; Brombin, Chiara; Ambrosi, Alessandro; Danese, Silvio; Mignatti, Paolo; Blasi, Francesco; D'Alessio, Silvia

    2015-11-15

    The urokinase-type plasminogen activator receptor (uPAR) has a well-established role in cancer progression, but it has been little studied at earlier stages of cancer initiation. Here, we show that uPAR deficiency in the mouse dramatically reduces susceptibility to the classical two-stage protocol of inflammatory skin carcinogenesis. uPAR genetic deficiency decreased papilloma formation and accelerated keratinocyte differentiation, effects mediated by Notch1 hyperactivation. Notably, Notch1 inhibition in uPAR-deficient mice rescued their susceptibility to skin carcinogenesis. Clinically, we found that human differentiated keratoacanthomas expressed low levels of uPAR and high levels of activated Notch1, with opposite effects in proliferating tumors, confirming the relevance of the observations in mice. Furthermore, we found that TACE-dependent activation of Notch1 in basal kerantinocytes was modulated by uPAR. Mechanistically, uPAR sequestered TACE within lipid rafts to prevent Notch1 activation, thereby promoting cell proliferation and tumor formation. Given that uPAR signaling is nonessential for normal epidermal homeostasis, our results argue that uPAR may present a promising disease-specific target for preventing skin cancer development.

  16. Construction of Urokinase Mutant Glu154-mtcu-PA and Characterization of Its Properties.

    PubMed

    Peng, Gui-Hong; Ma, Zhong; Xue, Yu-Ming; Chen, Yu-Hong; Zhu, De-Xu

    1997-01-01

    The recombinant single chain urokinase-type plasminogen activator (rscu-PA) and a mutant constructed by in vitro site-specific mutagenesis of Argl54 in rscu-PA to Glul54 (Glul54-mscu-PA) were both expressed in E. coli. The expressed products were both purified to homogeneity by in vitro denaturation and renaturation, followed by Zn(2+) selective precipitation and immuno-affinity chromatography. The plasmin sensitivity assay indicated that the activation of this single chain Glul54-mscu-PA by plasmin was essentially identical to that of rscu-PA. After activation by plasmin, the kinetic constants against synthetic substrate S2444 of the resulted two chain form of Glul54-mscu-PA (Glul54-mtcu-PA) and that of rscu-PA (rtcu-PA) were 87 &mgr;M and 80 &mgr;M, respectively, which indicated that the catalytic active site of the Glul54-mtcu-PA was not changed by the mutation. Whereas, both (125)I-fibrin plasma-clot lysis and fibrinogenolysis in plasma showed that the Glul54-mtcu-PA possessed a better affinity and selectivity for fibrin than rtcu-PA, even better than rscu-PA.

  17. Mutation of Arg154 to Gly154 in urokinase augments its fibrin-specificity.

    PubMed

    Peng, G; Ma, Z; Kuai, L; Zhu, D

    1997-04-01

    Rscu-PA and its mutant constructed by in vitro site specific mutagenesis of Arg154 in rscu-PA to Gly154 (mscu-PA) were both expressed in Escherichia coli. After in vitro denaturation and renaturation, the rscu-PA and mscu-PA were purified to homogeneity by Zn2+ selective precipitation, anti-u-PA IgG-sepharose CL 4B affinity chromatography. After activation by plasmin, the kinetic constants for the resultant mtcu-PA against synthetic substrate S2444 hydrolysis were found to be essentially identical to rtcu-PA, suggesting that no impairment had been exerted on the catalytic active site of mtcu-PA. However, both 125I-fibrin plasma-clot lysis and fibrinogenolysis showed that mtcu-PA possessed a higher fibrinolytic activity but hardly any degradation of fibrinogen in plasma compared to rtcu-PA and rscu-PA. It was concluded that the substitution of Arg154 by Gly154 in tcu-PA promoted the fibrin-specificity of urokinase.

  18. Homocysteine and its thiolactone impair plasmin activity induced by urokinase or streptokinase in vitro.

    PubMed

    Kolodziejczyk-Czepas, Joanna; Talar, Beata; Nowak, Pawel; Olas, Beata; Wachowicz, Barbara

    2012-04-01

    Mechanisms of homocysteine (Hcy) contribution to thrombosis are complex and only partly recognized. The available data suggest that the prothrombotic activity of homocysteine may be not only a result of the changes in coagulation process and endothelial dysfunction, but also the dysfunction of fibrinolysis. The aim of the present work was to assess the effects of homocysteine (10-100 μM mM) and its thiolactone (HTL, 0.1-1 μM) on plasminogen and plasmin functions in vitro. The amidolytic activity of generated plasmin in Hcy or HTL-treated plasminogen and plasma samples was measured by the hydrolysis of chromogenic substrate. Effects of Hcy and HTL on proteolytic activity of plasmin were monitored electrophoretically, by using of fibrinogen as a substrate. The exposure of human plasma and purified plasminogen to Hcy or HTL resulted in the decrease of urokinase-induced plasmin activity. In plasminogen samples treated with the highest concentration of homocysteine (100 μM) or thiolactone (1 μM), the activity of plasmin was inhibited by about 50%. In plasma samples, a reduction of amidolytic activity by about 30% (for 100 μM Hcy) and 40% (for 1 μM HTL), was observed. Both Hcy and HTL were also able to diminish the streptokinase-induced proteolytic activity of plasmin. In conclusion, the results obtained in this study demonstrate that Hcy and HTL may affect fibrinolytic properties of plasminogen and plasma, leading to the decrease of plasmin activity.

  19. 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.

  20. Mice Deficient in Urokinase-Type Plasminogen Activator Have Delayed Healing of Tympanic Membrane Perforations

    PubMed Central

    Du, Chun; Wilczynska, Malgorzata; Hellström, Sten; Ny, Tor

    2012-01-01

    Mice deficient in plasminogen, the precursor of plasmin, show completely arrested healing of tympanic membrane (TM) perforations, indicating that plasmin plays an essential role in TM healing. The activation of plasminogen to plasmin is performed by two plasminogen activators (PAs), urokinase-type PA (uPA) and tissue-type PA (tPA). To elucidate the functional roles of PAs in the healing of TM perforations, we investigated the phenotypes of single gene-deficient mice lacking uPA (uPA−/−) or tPA (tPA−/−) after TM perforation. Delayed healing of TM perforations was observed in uPA−/− mice but not tPA−/− mice. The migration of keratinocytes was clearly delayed and seemed to be misoriented in uPA−/− mice. Furthermore, fibrin deposition and the inflammatory response were persistent in these mice. Our findings demonstrate that uPA plays a role in the healing of TM perforations. The observed phenotypes in uPA−/− mice are most likely due to the reduced generation of plasmin. PMID:23236466

  1. Urokinase gene transfer augments angiogenesis in ischemic skeletal and myocardial muscle.

    PubMed

    Traktuev, Dmitry O; Tsokolaeva, Zoya I; Shevelev, Alexander A; Talitskiy, Konstantin A; Stepanova, Victoria V; Johnstone, Brian H; Rahmat-Zade, Tahmina M; Kapustin, Alexander N; Tkachuk, Vsevolod A; March, Keith L; Parfyonova, Yelena V

    2007-11-01

    Urokinase plasminogen activator (uPA) is required for both endogenous and vascular endothelial growth factor (VEGF)-augmented angiogenesis in normal tissues, leading us to hypothesize that uPA augmentation by gene transfer might promote angiogenesis in ischemic tissues. Overexpression of uPA was studied in rat myocardial infarction (MI) and mouse hind limb ischemia models and compared with VEGF overexpression effects. Animals were divided into control and three experimental groups (n = 6), receiving intramuscular injections of plasmids as follows: (i) control (empty vector or expressing beta-galactosidase); (ii) uPA; (iii) VEGF(165); (iv) a 1:1 mixture of uPA and VEGF(165). The capillary densities in both ischemic models were greater (P < 0.05) in tissues treated with uPA, VEGF, or a combination of both than in controls. Infarct size was reduced in hearts from uPA and VEGF experimental groups compared with controls (P < 0.05). Local overexpression of uPA induced a marked increase in the number of macrophages and myofibroblasts present within infarcts. Hind limb blood flow was greater in all experimental groups by day 10 (P < 0.05). Overall, the effects of uPA and VEGF were uniformly comparable. Additional analysis revealed association of local edema with VEGF but not with uPA treatment. This study established that uPA gene therapy effectively induces functionally significant angiogenesis in models of acute MI and hind limb ischemia.

  2. Loss of Urokinase Receptor Sensitizes Cells to DNA Damage and Delays DNA Repair

    PubMed Central

    Narayanaswamy, Pavan B.; Hodjat, Mahshid; Haller, Hermann; Dumler, Inna; Kiyan, Yulia

    2014-01-01

    DNA damage induced by numerous exogenous or endogenous factors may have irreversible consequences on the cell leading to cell cycle arrest, senescence and cell death. The DNA damage response (DDR) is powerful signaling machinery triggered in response to DNA damage, to provide DNA damage recognition, signaling and repair. Most anticancer drugs induce DNA damage, and DNA repair in turn attenuates therapeutic efficiency of those drugs. Approaches delaying DNA repair are often used to increase efficiency of treatment. Recent data show that ubiquitin-proteasome system is essential for signaling and repair of DNA damage. However, mechanisms providing regulation of proteasome intracellular localization, activity, and recruitment to DNA damage sites are elusive. Even less investigated are the roles of extranuclear signaling proteins in these processes. In this study, we report the involvement of the serine protease urokinase-type plasminogen activator receptor (uPAR) in DDR-associated regulation of proteasome. We show that in vascular smooth muscle cells (VSMC) uPAR activates DNA single strand break repair signaling pathway. We provide evidence that uPAR is essential for functional assembly of the 26S proteasome. We further demonstrate that uPAR mediates DNA damage-induced phosphorylation, nuclear import, and recruitment of the regulatory subunit PSMD6 to proteasome. We found that deficiency of uPAR and PSMD6 delays DNA repair and leads to decreased cell survival. These data may offer new therapeutic approaches for diseases such as cancer, cardiovascular and neurodegenerative disorders. PMID:24987841

  3. Expression and localization of urokinase-type plasminogen activator receptor in bovine cumulus-oocyte complexes.

    PubMed

    García, Daniela C; Miceli, Dora C; Rizo, Gabriela; García, Elina V; Valdecantos, Pablo A; Roldán-Olarte, Mariela

    2016-04-01

    Urokinase-type plasminogen activator (uPA) is a serine protease involved in extracellular matrix remodeling through plasmin generation. uPA usually binds to its receptor, uPAR, which is anchored to the plasma membrane through a glycosylphosphatidylinositol anchor. uPA/uPAR binding increases proteolytic activity in the neighborhood of the cells containing uPAR and activates intracellular signaling pathways involved in extracellular matrix remodeling, cell migration and proliferation. The aim of this work was to study the expression of uPA, uPAR and plasminogen activator inhibitor-1 (PAI-1) in immature and in vitro matured bovine cumulus-oocyte complexes (COCs). uPA is only expressed in the cumulus cells of immature and in vitro matured COCs, while uPAR and PAI-1 are expressed in both the cumulus cells and the immature and in vitro matured oocytes. In addition, uPAR protein was localized by confocal microscopy in the plasma membrane of oocytes and cumulus cells of immature COCs. Results from this research led us to hypothesize that the uPA/uPAR interaction could cause the local production of uPA-mediated plasmin over oocyte and cumulus cell surface; plasmin formation could also be regulated by PAI-1.

  4. 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.

  5. 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

  6. Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

    PubMed Central

    Haastrup, Eva; Grau, Katrine; Eugen-Olsen, Jesper; Thorball, Christian; Kessing, Lars Vedel; Ullum, Henrik

    2014-01-01

    Objectives Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. Methods suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register. Results For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1st to the 4th quartile (HR = 1.72, 95% CI: 1.11–2.69). For women, it increased by 108% from the 1st to the 4th quartile (HR = 2.08, 95% CI: 1.45–2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002). Conclusions High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression. PMID:25329298

  7. Serum levels of soluble urokinase plasminogen activator receptor as a new inflammatory marker in adolescent obesity.

    PubMed

    Can, Ummugulsum; Buyukinan, Muammer; Yerlikaya, Fatma Humeyra

    2017-03-01

    Obesity is known for low-grade inflammatory state with enhanced production of inflammatory mediators in children and adolescents. Soluble urokinase plasminogen activator receptor (suPAR) can be generated as a pro-inflammatory marker. This study was conducted to evaluate the role of suPAR, and its association with leptin, adiponectin, interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP) and fibrinogen in adolescent obesity. A total of 98 participants, 55 obese individuals and 43 healthy controls, aged between 10 and 17 yr, were included in the study. Serum suPAR, IL-6, leptin and adiponectin were measured using ELISA method. Serum suPAR, IL-6, fibrinogen, hsCRP and leptin levels in obese individuals were significantly higher than those of controls (P<0.05 & P<0.001). Serum adiponectin levels in obese individuals were significantly lower than those of controls (P<0.01). Our findings showed that suPAR, IL-6, fibrinogen, hsCRP and leptin were significantly higher in the obese individuals than those of controls. suPAR may be a good novel biomarker for systemic subclinical inflammation and immune activation linked to adolescent obesity.

  8. Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression.

    PubMed Central

    de Vries, T. J.; Quax, P. H.; Denijn, M.; Verrijp, K. N.; Verheijen, J. H.; Verspaget, H. W.; Weidle, U. H.; Ruiter, D. J.; van Muijen, G. N.

    1994-01-01

    Degradation of the extracellular matrix and other tissue barriers by proteases like plasminogen activators (PAs) is a prerequisite for neoplastic growth and metastasis. Recently, we reported that highly metastatic behavior of human melanoma cells in nude mice correlates with urokinase-type PA (u-PA) expression and activity and with PA inhibitor type 1 and 2 (PAI-1, PAI-2) expression. Here we report on the occurrence of components of the PA system in the various stages of human melanoma tumor progression in situ. We studied the protein distribution on freshly frozen lesions of common nevocellular nevi (n = 25), dysplastic (= atypical) nevi (n = 16), early primary melanomas (n = 8), advanced primary melanomas (n = 11), and melanoma metastases (n = 17). Tissue-type PA was present in endothelial cells in all lesions, whereas in metastases it could be detected in tumor cells in a minority of the lesions. u-PA, its receptor, PAI-1, and PAI-2 could not be detected in benign and in early stages but appeared frequently in advanced primary melanoma and melanoma metastasis lesions. u-PA was detected in stromal cells and in tumor cells at the invasive front, the u-PA receptor and PAI-2 in tumor cells, and PAI-1 in the extracellular matrix surrounding tumor cells. Localization of the corresponding messenger RNAs and enzyme activities revealed a similar distribution. We conclude that plasminogen activation is a late event in melanoma tumor progression. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8291613

  9. Acute hepatitis after amiodarone infusion.

    PubMed

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

    2015-10-16

    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.

  10. General-purpose infusion pumps.

    PubMed

    1998-01-01

    General-purpose infusion pumps deliver liquid medications to patients through intravenous or epidural routes at specified flows. They are most often used in hospitals and alternative care settings (e.g., physician' offices, patients' homes) when liquid medications need to be administered with greater accuracy or at higher flows than can be provided through a manually adjusted gravity administration set. In this Update of our February 1997 Evaluation of infusion pumps (Health Devices 26[2]), we tested 3 additional pumps from 3 suppliers. We also rated and ranked them in comparison with the 16 units from the February 1997 study that are still being produced. With a few exceptions, we tested the new pumps against the same criteria and using the same test methods as those in the previous Evaluation. However, for this Update, the focus of our findings has broadened: although we continue to place strong emphasis on the pumps' protection against gravity free-flow, we also give significant weight to their overall safety, performance, and human factors design. As a result, our ratings and rankings scheme has changed, affecting the rankings of some of the previously evaluated units. Of the 19 currently available units that have been evaluated to date, we rated 13 units Acceptable, with 5 of those units ranked above the other 8. A further 5 units were rated Conditionally Acceptable; we consider them Acceptable if they are used with the available free-flow protection. And 1 unit had performance problems that caused us to rate it Unacceptable (this unit has been recalled by its supplier; see the inset on page 162). As always, we caution readers not to base selection and purchasing decisions on our conclusions alone, but on a thorough understanding of the issues behind those conclusions, which can be gained by reading this Evaluation in its entirety and carefully reviewing the February 1997 issue.

  11. Accidental hypoglycaemia caused by an arterial flush drug error: a case report and contributory causes analysis.

    PubMed

    Gupta, K J; Cook, T M

    2013-11-01

    In 2008, the National Patient Safety Agency (NPSA) issued a Rapid Response Report concerning problems with infusions and sampling from arterial lines. The risk of blood sample contamination from glucose-containing arterial line infusions was highlighted and changes in arterial line management were recommended. Despite this guidance, errors with arterial line infusions remain common. We report a case of severe hypoglycaemia and neuroglycopenia caused by glucose contamination of arterial line blood samples. This case occurred despite the implementation of the practice changes recommended in the 2008 NPSA alert. We report an analysis of the factors contributing to this incident using the Yorkshire Contributory Factors Framework. We discuss the nature of the errors that occurred and list the consequent changes in practice implemented on our unit to prevent recurrence of this incident, which go well beyond those recommended by the NPSA in 2008. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

  12. The Infusion Approach to Teacher Development.

    ERIC Educational Resources Information Center

    Kowalski, Ellen M.

    1995-01-01

    The underlying premise of infusion is that information about individuals with disabilities must be more systematically integrated throughout an entire curriculum. This article describes the infusion approach to teacher development, explaining three central premises, providing sample program applications for each premise, and discussing brain…

  13. 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…

  14. Problems identified with home infusion pumps.

    PubMed

    Koeppen, M A; Caspers, S M

    1994-01-01

    A variety of infusion pumps and devices are available on the market today. In this article, the authors examine these products based on questionnaires sent out to typical consumers, including hospitals and caregivers. Using the results of this questionnaire, the authors identify whether or not users of home infusion pumps and devices find them difficult to operate.

  15. The U.S. home infusion market.

    PubMed

    Monk-Tutor, M R

    1998-10-01

    Medicare legislation stimulated the development of home care services but also resulted in fragmentation of service components. In the 1980s, prospective pricing and diagnosis-related groups, and resulting pressures to reduce inpatient length of stay, prompted additional growth of the industry. Even so, in 1995 home care represented only 3% of total national expenditures on health care. The annual growth rate of the home infusion industry dropped from 64% in 1982-86 to 24% in 1986-93. While revenue per patient for home infusion is expected to decrease under managed care, an increasing number of patients will support continued market growth. The home infusion market is highly competitive, with only a few large national providers and many small local providers. In 1996, 29% of acute care hospitals provided or were developing a home care program. Community pharmacists' options in the home infusion area include independent services, partnerships, joint ventures, contracts with hospitals, and franchises. The home infusion market is being integrated into alternative sites, such as ambulatory infusion centers (AICs), as providers attempt to diversify to maintain managed care contracts. AICs provide infusion therapy and nursing to noninstitutionalized, nonhome-bound patients. Untapped sources for future growth of the infusion market include long-term-care facilities. More consistent studies of the home care market are needed. Despite slowed growth in recent years, home care has a strong market in the United States.

  16. 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…

  17. Treatment of a patient with congenital analbuminemia with atorvastatin and albumin infusion

    PubMed Central

    Del Ben, Maria; Angelico, Francesco; Loffredo, Lorenzo; Violi, Francesco

    2013-01-01

    Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, apart from ease of fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for safely treating both hypercholesterolemia and analbuminemia in order to eventually decrease the atherosclerotic risk. We report a case of congenital analbuminemia (1.0 g/dL) in a 38-year-old male with hypercholesterolemia (range: 406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated dilation (FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was associated with the appearance of peripheral edema. Two-months of infusion with albumin improved FMD (7%) and reduced serum cholesterol (273 mg/dL), supporting the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment, together with periodical albumin infusions, may contribute to the safe reduction of cardiovascular risk. PMID:24303462

  18. Impact of chronic fructose infusion on hepatic metabolism during TPN administration.

    PubMed

    Donmoyer, Christine M; Lacy, D Brooks; Zhang, Yiqun; Chen, Sheng-Song; McGuinness, Owen P

    2002-12-01

    During chronic total parenteral nutrition (TPN), net hepatic glucose uptake (NHGU) is markedly elevated. However, NHGU is reduced by the presence of an infection. We recently demonstrated that a small, acute (3-h) intraportal fructose infusion can correct the infection-induced impairment in NHGU. The aim of this study was to determine whether the addition of fructose to the TPN persistently enhances NHGU in the presence of an infection. TPN was infused continuously into the inferior vena cava of chronically catheterized dogs for 5 days. On day 3, a bacterial clot was implanted in the peritoneal cavity, and either saline (CON, n = 5) or fructose (+FRUC, 1.0 mg. kg(-1). min(-1), n = 6) infusion was included with the TPN. Forty-two hours after the infection was induced, hepatic glucose metabolism was assessed in conscious dogs with arteriovenous and tracer methods. Arterial plasma glucose concentration was lower with chronic fructose infusion (120 +/- 4 vs. 131 +/- 3 mg/dl, +FRUC vs. CON, P < 0.05); however, NHGU was not enhanced (2.2 +/- 0.5 vs. 2.8 +/- 0.4 mg. kg(-1). min(-1)). Acute removal of the fructose infusion dramatically decreased NHGU (2.2 +/- 0.5 to -0.2 +/- 0.5 mg. kg(-1). min(-1)), and net hepatic lactate release also fell (1.6 +/- 0.3 to 0.5 +/- 0.3 mg. kg(-1). min(-1)). This led to an increase in the arterial plasma glucose (Delta13 +/- 3 mg/dl, P < 0.05) and insulin (Delta5 +/- 2 micro U/ml) concentrations and to a decrease in glucagon (Delta-11 +/- 3 pg/ml) concentration. In conclusion, the addition of chronic fructose infusion to TPN during infection does not lead to a persistent augmentation of NHGU.

  19. Renal electrolyte excretion and renin release during calcium and parathormone infusions in conscious rabbits.

    PubMed Central

    Peart, W S; Roddis, S A; Unwin, R J

    1986-01-01

    Following a random block experimental design in each case, three repeated measurement studies were carried out in three different groups of conscious rabbits, to investigate the renal effects of increasing doses of intravenous calcium chloride (CaCl2) and bovine parathyroid hormone (PTH). In the first study, each rabbit received either CaCl2 (0.15, 0.3, 0.5 or 1.0 mg kg-1 min-1) or vehicle alone (control) for 160 min. In the second study, rabbits were given either PTH (0.15 microgram kg-1 min-1), CaCl2 (1.0 mg kg-1 min-1), PTH plus CaCl2 (0.15 microgram kg-1 min-1 and 1.0 mg kg-1 min-1, respectively) or vehicle alone; PTH was infused for just over 60 min. In the third study, a much smaller dose (0.05 mg kg-1 min-1) of CaCl2 was infused for 100 min. CaCl2 infusion produced a striking fall in fractional excretion of sodium of at least 50% (P less than 0.01), but this was not dose related, being almost maximal at the smaller doses infused. Although this effect was evident in the absence of any changes in total plasma calcium concentration at the lower doses of CaCl2, renal calcium excretion was increased between 2- and 20-fold (P less than 0.01) at all doses infused. Fractional excretion of chloride doubled at the two higher doses of CaCl2 (P less than 0.01), but potassium excretion was unchanged. There were no consistent alterations in mean arterial blood pressure, effective renal plasma flow, glomerular filtration rate or plasma renin activity (PRA); total plasma calcium concentration was consistently elevated only during infusion of the high dose by just under 1 mmol l-1. PTH infusion had no measured effect on fractional excretion of sodium or renal calcium excretion, but doubled fractional potassium excretion (P less than 0.05). Heart rate and PRA increased (P less than 0.01 and less than 0.05, respectively), the latter by 50%, but systemic pressure and renal haemodynamics were not significantly affected. By contrast, PTH infused with CaCl2 produced a 4-fold rise

  20. 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.

  1. The effect of intracarotid vasopressin infusion on ACTH release in neurohypophysectomized, conscious dogs.

    PubMed

    Raff, H; Papanek, P E; Liard, J F; Cowley, A W

    1994-09-01

    Neurohypophysectomy (NHX) attenuates the adrenocorticotropic hormone (ACTH) response to arterial hypotension but not corticotropin-releasing hormone (CRH) or insulin-induced hypoglycemia in conscious dogs. The purpose of the present study was to determine if increasing vasopressin (AVP) in the cephalic circulation by carotid infusion normalizes the ACTH response to hypotension attenuated by NHX. Five male, conditioned dogs underwent controlled, acute decreases in arterial pressure (by approximately 25 mmHg) by infusion of sodium nitroprusside (NP) before and > 4 wk after selective NHX. ACTH increased from 40 +/- 3 to 242 +/- 79 pg/ml during NP in the intact state. This response was greatly attenuated after NHX (peak ACTH 81 +/- 15 pg/ml). Simultaneous intravenous infusion of AVP (12.5 ng/min) had a small, augmenting effect on the ACTH response to NP (peak ACTH 120 +/- 27 pg/ml). Intracarotid AVP (12.5 ng/min) greatly augmented the ACTH response to NP (peak ACTH 202 +/- 26 pg/ml) such that it was no longer different from the intact response. Neither intravenous nor intracarotid AVP infusion per se had a great effect on ACTH. A normal ACTH response to hypotension requires an intact neurohypophysis and is mediated by a cephalic action of magnocellular AVP.

  2. Hemodynamic changes with high infusion rates of lipid emulsion. Experimental study in swine.

    PubMed

    Udelsmann, Artur; Melo, Marcos De Simone

    2015-11-01

    To evaluate hemodynamic changes caused by sole intravenous infusion of lipid emulsion with doses recommended for treatment of drug-related toxicity. Large White pigs underwent general anesthesia, tracheal intubation was performed, and mechanical ventilation was instituted. Hemodynamic variables were recorded using invasive blood pressure and pulmonary artery catheterization. Baseline hemodynamic measurements were obtained after a 30-minute stabilization period. An intravenous bolus injection of 20% lipid emulsion at 1.5 ml/kg was administered. Additional hemodynamic measurements were made after 1 minute, followed by a continuous intravenous lipid infusion of 0.25 ml/kg/min. Further measurements were carried out at 10, 20 and 30 minutes, when the infusion was doubled to 0.5 ml/kg/min. Assessment of hemodynamic changes were then made at 40, 50 and 60 minutes. Lipid infusion did not influence cardiac output or heart rate, but caused an increase in arterial blood pressure, mainly pulmonary blood pressure due to increased vascular resistance. Ventricular systolic stroke work consequently increased with greater repercussions on the right ventricle. In doses used for drug-related toxicity, lipid emulsion cause significant hemodynamic changes with hypertension, particularly in the pulmonary circulation and increase in vascular resistance, which is a factor to consider prior to use of these solutions.

  3. Cardiopulmonary effects of dobutamine and norepinephrine infusion in healthy anesthetized alpacas.

    PubMed

    Vincent, Caitlin J; Hawley, Alexander T; Rozanski, Elizabeth A; Lascola, Kara M; Bedenice, Daniela

    2009-10-01

    To characterize the cardiopulmonary effects of dobutamine and norepinephrine infusion in isoflurane-anesthetized healthy alpacas. 8 adult alpacas. Initial baseline cardiovascular, respiratory, and metabolic variables were obtained 30 minutes after induction of isoflurane anesthesia in 8 alpacas (3 females and 5 sexually intact males). Four treatments (dobutamine at 4 and 8 microg/kg/min and norepinephrine at 0.3 and 1 microg/kg/min) were administered in random order via constant rate infusion over 15 minutes, followed by repeat measurements of cardiopulmonary values and a 20-minute washout period. Subsequent baseline and posttreatment measurements were similarly repeated until both drugs and dosages were administered to each animal. Baseline data in awake alpacas were obtained 18 to 24 hours following recovery from anesthesia. Both dobutamine and norepinephrine significantly increased cardiac index and arterial blood pressure from baseline values. Similar increases in hemoglobin concentration, oxygen content, and oxygen delivery were observed following administration of each drug at either dosage. Only dobutamine, however, reduced relative oxygen consumption while improving overall tissue oxygenation. Furthermore, heart rate was selectively enhanced by dobutamine and systemic vascular resistance by norepinephrine. Norepinephrine infusion resulted in dose-dependent changes in cardiopulmonary variables. Results indicated that both dobutamine and norepinephrine were appropriate choices to improve cardiac index, mean arterial pressure, and overall oxygen delivery in alpacas with isoflurane-induced hypotension. Careful titration by use of low infusion rates of dobutamine and norepinephrine is recommended to avoid potential arrhythmogenic effects and excessive vasoconstriction, respectively.

  4. Mesenteric artery ischemia

    MedlinePlus

    ... bowel - mesenteric; Dead gut - mesenteric; Atherosclerosis - mesenteric artery; Hardening of the arteries - mesenteric artery ... the aorta, the main artery from the heart. Hardening of the arteries occurs when fat, cholesterol, and ...

  5. 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 ...

  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. Infusion of 2.5 meq/min of Lactic Acid minimally increases CO2 production compared to an isocaloric glucose infusion in healthy anesthetized, mechanically ventilated pigs.

    PubMed

    Zanella, Alberto; Giani, Marco; Redaelli, Sara; Mangili, Paolo; Scaravilli, Vittorio; Ormas, Valentina; Costanzi, Marco; Albertini, Mariangela; Bellani, Giacomo; Patroniti, Nicolò; Pesenti, Antonio

    2013-11-11

    Blood acidification by lactic acid infusion converts bicarbonate to CO2. This effect can be exploited to increase the transmembrane PCO2 gradient of an extracorporeal membrane lung, resulting in a significant increase of extracorporeal CO2 removal. Lactic acid, however, is an energetic substrate and its metabolism might increase total body CO2 production (VCO2), limiting the potential beneficial effects of this technique. The aim of our study was to compare VCO2 during isocaloric infusion of lactic acid or glucose. Six pigs (45 ± 5 kg) were sedated and mechanically ventilated. Estimated caloric needs were 2,300-2,400 Kcal/die (95 to 100 Kcal/h). A sequence of two steps lasting four hours each was performed: 1) Glucose, 97 kcal/h were administered as 50% glucose solution, and 2) Lactic Acid, approximately 48.5 kcal/h were administered as lactic acid and approximately 48.5 kcal/h as 50% glucose solution. This sequence was repeated three times with two-hour intervals. Every hour VCO2, arterial blood gases and lactate were measured. Blood glucose level was kept constant by titrating an insulin infusion, ventilation was adjusted to maintain arterial PCO2 at 50 mmHg, a normal value for our animal model. During Lactic Acid steps VCO2 increased less than 5% compared to the Glucose steps (282 vs. 269 ml/min, P < 0.05); blood glucose did not differ between the two groups (respectively 101 ± 12 vs. 103 ± 8 mg/dl). Arterial lactate was always lower than 3 mmol/L. Arterial pH was lower during Lactic Acid steps (7.422 vs. 7.445, P < 0.05). Replacing 50% of the caloric input with lactic acid increased total CO2 production by less than 5% compared to an equal caloric load provided entirely by a 50% glucose solution.

  8. Fibrin sheaths in central venous port catheters: treatment with low-dose, single injection of urokinase on an outpatient basis

    PubMed Central

    Chang, De-Hua; Mammadov, Kamal; Hickethier, Tilman; Borggrefe, Jan; Hellmich, Martin; Maintz, David; Kabbasch, Christoph

    2017-01-01

    Purpose Evaluation of the efficacy of single-shot, low-dose urokinase administration for the treatment of port catheter-associated fibrin sheaths. Methods Forty-six patients were retrospectively evaluated for 54 episodes of port catheter dysfunction. The presence of a fibrin sheath was detected by angiographic contrast examinations. On an outpatient basis, patients subsequently received thrombolysis consisting of a single injection of urokinase (15.000 IU in 1.5 mL normal saline) through the port system. A second attempt was made in cases of treatment failure. Patients were followed up for technical success, complications and long-term outcome. Results Port dysfunction occurred at a median of 117 days after implantation (range: 7–825 days). The technical success after first port dysfunction by thrombolysis was 87% (40/46); thereof, initial thrombolysis was effective in 78% (36/46). Nine patients (20%) received a second dose of urokinase after previous treatment failure. Follow-up was available for 26 of 40 patients after successful thrombolysis. In 8 of these, rethrombosis occurred after a median of 98 days (range: 21–354 days), whereby rethrombolysis was effective in 5 of 7 (63%) patients. The overall success of all thrombolyses performed was 70% (45/64). No procedure-related technical or clinical complications occurred. After first favorable thrombolysis, a Kaplan–Meier analysis yielded a 30-, 90- and 180-day probability of patency of 96%, 87% and 81%. Conclusion Thrombolytic therapy on an outpatient basis appears to be a safe and efficient. Three-month patency rates are comparable to more invasive treatment options, including catheter exchange over a guide wire and percutaneous fibrin sheath stripping. PMID:28182117

  9. Effect of converting enzyme inhibition on the renal haemodynamic responses to noradrenaline infusion in the rat.

    PubMed Central

    Arundell, L. A.; Johns, E. J.

    1982-01-01

    1 The renal haemodynamic responses to a close arterial infusion of noradrenaline (29.7-177.9 nmol kg-1 h-1) were measured in rats anaesthetized with pentobarbitone. Systemic blood pressure was unaffected by noradrenaline infusion at this dose level. Renal blood flow was significantly reduced by 16% while glomerular filtration rate remained unchanged. These responses resulted in a rise in filtration fraction of some 10%. 2 In a separate group of animals, noradrenaline infusion in this manner and at similar dose rate increased plasma renin activity approximately 3 fold. 3 Continuous infusion of the angiotensin converting enzyme inhibitor, teprotide (3.36 mumol kg-1 h-1), had no measurable effect on systemic blood pressure, renal blood flow, glomerular filtration rate or filtration fraction. 4 Infusion of noradrenaline into these animals receiving teprotide caused a significant fall in renal blood flow of 16%. There was a fall in glomerular filtration rate of some 17% which was significantly different from the response observed in the animals not receiving teprotide. There was a consequent small but insignificant fall in filtration fraction. 5 These data show that the regulation of glomerular filtration rate in response to the vasoconstrictor drug, noradrenaline, is partly mediated via the renin-angiotensin system. They provide evidence for a role of intrarenal angiotensin II in regulating glomerular filtration by causing efferent arteriolar vasoconstriction. PMID:6175369

  10. A comparative study of Sterofundin and Ringer lactate based infusion protocol in scoliosis correction surgery

    PubMed Central

    Sharma, Ashima; Yadav, Monu; Kumar, B. Rajesh; Lakshman, P. Sai; Iyenger, Raju; Ramchandran, Gopinath

    2016-01-01

    Background: A major change in anesthesia practice as regards to intraoperative infusion therapy is the present requirement. Switching over to balanced fluids can substantially decrease the incidence of lactic acidosis and hyperchloremic acidosis. The deleterious effects of unbalanced fluids are more recognizable during major surgeries. We prospectively studied the influence of Sterofundin (SF) and Ringer lactate (RL) on acid–base changes, hemodynamics, and readiness for extubation during scoliosis surgery. Subjects and Methods: Thirty consecutive children posted for scoliosis surgery were randomized to receive either RL (n = 15) or SF (n = 15) as intraoperative fluid at 10 mg/kg/h. Fluid boluses were added according to the study fluid algorithm. Arterial blood was sampled and analyzed at hourly intervals during surgery. Red blood cell transfusion was guided by hematocrit below 27. Patients were followed for 24 h postoperatively in the Intensive Care Unit. Results: There was no statistically significant difference in the volume of infused fluid (2400 ± 512 ml in Group RL and 2200 ± 640 ml in Group SF. There were no significant changes in pH of patients infused with SF. Statistically, significant higher lactate levels were seen in RL-infused group. The strong ion difference was decreased in both groups, but it normalized earlier with SF. Conclusions: SF-infused patients had nonremarkable changes in acid–base physiology in scoliosis surgery. PMID:27746547

  11. The haemodynamic effects of bolus versus slower infusion of intravenous crystalloid in healthy volunteers.

    PubMed

    Ukor, Ida F; Hilton, Andrew K; Bailey, Michael J; Bellomo, Rinaldo

    2017-05-30

    This pilot study aimed to characterise the haemodynamic effect of 1L of IV normal saline (NS) administered as a rapid versus slow infusion on cardiac output (CO), heart rate (HR), systemic blood pressures, and carotid blood flow in six healthy volunteers. Six healthy male volunteers aged 18-65years were randomized to receive 1L NS given over 30min or 120min. On a subsequent study session the alternate fluid regimen was administered. Haemodynamic data was gathered using a non-invasive finger arterial pressure monitor (Nexfin®), echocardiography and carotid duplex sonography. Time to micturition and urine volume was also assessed. Compared to baseline, rapid infusion of 1L of saline over 30min produced a fall in Nexfin®-measured CO by 0.62L/min (p<0.001), whereas there was a marginal but significant increase during infusion of 1L NS over 120min of 0.02L/min (p<0.001). This effect was mirrored by changes in HR and blood pressure (BP) (p<0.001). There were no significant changes in carotid blood flow, time to micturition, or urine volume produced. Slower infusion of 1L NS in healthy male volunteers produced a greater increase in CO, HR and BP than rapid infusion. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  12. Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors.

    PubMed

    Hiendlmeyer, Elke; Regus, Susanne; Wassermann, Stella; Hlubek, Falk; Haynl, Angela; Dimmler, Arno; Koch, Claudia; Knoll, Claudia; van Beest, Moniek; Reuning, Ute; Brabletz, Thomas; Kirchner, Thomas; Jung, Andreas

    2004-02-15

    Expression of the urokinase plasminogen activator (uPA) increases during the progression of colorectal tumors from adenomas to carcinomas. The highest amounts of uPA are found at the invasion front of carcinomas, which also displays a strong expression of nuclear beta-catenin and is therefore a region expressing beta-catenin target genes at high levels. Here we show that beta-catenin contributes to the transactivation of uPA. Therefore, beta-catenin might have an impact on the capacity of colorectal tumors for invasion and metastasis, as well as dormancy, which are hallmarks of cancer.

  13. [Correction of hemodynamics and heart rate disorders in paitients with right coronary artery disease].

    PubMed

    Luk'ianova, I Iu; Sokolov, Iu V; Korotkevich, I A; Katasonov, S P

    2013-01-01

    To analyze a correlation between sino-atrial node automatic activity and atrio-ventricular conductivity in patients with lower acute myocardial infarction (AMI) and atrio-ventricular blockade II-III (AVB) during infusion therapy. Retrospective analysis of care for patients with AMI and AVB was carried out. Infusion therapy effects were studied in 12 patients with right coronary artery disease and AVB. Infusion therapy in patients with lower acute myocardial infarction, atrio-ventricular blockade and right ventricular failure corrects haemodynamic and dromotropic disturbances. Systolic arterial pressure (SAP) increased to 100,4 mmHg (9,9) after infusion of 400 mLin comparison with SAP after infusion of 200 mL (p = 0.003), Diastolic arterial pressure (DAP) increased to 58,7 mmHg (6,8) in comparison with DAP after infusion of 200 mL (p = 0.011), central venous pressure (CVP) decreased to 12.2 cmH2O (3,7) in comparison with CVP after infusion of 200 mL (p = 0.003). Mode of AVB degree indicator changed t 0O (0;0) (p = 0.028). Infusion volume therapy should be used for correction of right ventricular failure and disturbances of atrio-ventricular conductivity in case of right ventricular failure absence.

  14. Arterial Stiffness.

    PubMed

    Avolio, Alberto

    2013-04-01

    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.

  15. 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

  16. Air elimination capability in rapid infusion systems.

    PubMed

    Zoremba, N; Gruenewald, C; Zoremba, M; Rossaint, R; Schaelte, G

    2011-11-01

    Pressure infusion devices are used in clinical practice to apply large volumes of fluid over a short period of time. Although air infusion is a major complication, they have limited capability to detect and remove air during pressure infusion. In this investigation, we tested the air elimination capabilities of the Fluido(®) (The Surgical Company), Level 1(®) (Level 1 Technologies Inc.) and Ranger(®) (Augustine Medical GmbH) pressure infusion devices. Measurements were undertaken with a crystalloid solution during an infusion flow of 100, 200, 400 and 800 ml.min(-1). Four different volumes of air (25, 50, 100 and 200 ml) were injected as boluses in one experimental setting, or infused continuously over the time needed to perfuse 2 l saline in the other setting. The perfusion fluid was collected in an airtight infusion bag and the amount of air obtained in the bag was measured. The delivered air volume was negligible and would not cause any significant air embolism in all experiments. In our experimental setting, we found, during high flow, an increased amount of uneliminated air in all used devices compared with lower perfusion flows. All tested devices had a good air elimination capability. The use of ultrasonic air detection coupled with an automatic shutoff is a significant safety improvement and can reliably prevent accidental air embolism at rapid flows. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  17. Safety and Feasibility of Long-term Intravenous Sodium Nitrite Infusion in Healthy Volunteers

    PubMed Central

    Pluta, Ryszard M.; Oldfield, Edward H.; Bakhtian, Kamran D.; Fathi, Ali Reza; Smith, René K.; DeVroom, Hetty L.; Nahavandi, Masoud; Woo, Sukyung; Figg, William D.; Lonser, Russell R.

    2011-01-01

    Background Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion. Methodology Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008. All subjects provided written consent to participate. Twelve subjects (5 males, 7 females; mean age, 38.8±9.2 years (range, 21–56 years)) were intravenously infused with increasing doses of sodium nitrite for 48 hours (starting dose at 4.2 µg/kg/hr; maximal dose of 533.8 µg/kg/hr). Clinical, physiologic and laboratory data before, during and after infusion were analyzed. Findings The maximal tolerated dose for intravenous infusion of sodium nitrite was 267 µg/kg/hr. Dose limiting toxicity occurred at 446 µg/kg/hr. Toxicity included a transient asymptomatic decrease of mean arterial blood pressure (more than 15 mmHg) and/or an asymptomatic increase of methemoglobin level above 5%. Nitrite, nitrate, S-nitrosothiols concentrations in plasma and whole blood increased in all subjects and returned to preinfusion baseline values within 12 hours after cessation of the infusion. The mean half-life of nitrite estimated at maximal tolerated dose was 45.3 minutes for plasma and 51.4 minutes for whole blood. Conclusion Sodium nitrite can be safely infused intravenously at defined concentrations for prolonged intervals. These results should be valuable for developing studies to investigate new NO treatment paradigms for a variety of clinical disorders, including cerebral vasospasm after subarachnoid hemorrhage, and ischemia of the heart, liver, kidney and brain, as well as organ transplants, blood-brain barrier modulation and pulmonary hypertension. Clinical Trial Registration Information http

  18. 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.

  19. [INFUSION THERAPY IN RECONSTRUCTIVE MAXILLOFACIAL SURGERY].

    PubMed

    Yu, Zajcev A; Dubrovin, K V; Svetlov, V A

    2016-01-01

    Restricted infusion strategy in combination with antifibrinolytic agents such as aprotinin and tranexamic acid is effective for blood saving in maxillofacial surgery. But reduction of infusion volume can lead to intraoperative hypovolemia. The goal of this study was to assess compensative effect of different regimes of infusion therapy and antifibrinolytics on intraoperative volume status and electrolyte balance in reconstructive maxillofacial surgery. 65 patients were included in the study. There were 4 groups: (1) Infusion rate 8-12 mg/kg/h and acute normo/hypervolemic hemodilution; (2) 4-6 mg/kg/h and aprotinin 500,000 - 100,000 IU/4 hours; 3.6-8 mg/kg/h and tranexamic acid 8-10 mg/kg every 4 hours; 4.6-8 mg/kg/h and tranexamic acid 8-10 mg/kg every 4 hours and regional analgesia offacial nerves. We assessed parameters of central hemodynamic, peripheral perfusion, water-electrolyte balance and acid-base status. Different infusion strategies were effective in maintaining positive volume balance despite intraoperative blood loss and continuous diuresis. Hypovolemia or peripheral perfusion insufficiency weren't mentioned in the study. Water-electrolyte and acid-base balance was also secured in every case. Nevertheless, CVP and diuresis in the group with infusion rate 4-6 ml/kg/h were near the critical threshold and could be dangerous in poorly controlled intraoperative bleeding. The optimal infusion rate for surgical interventions in reconstructive maxillofacial surgery is 6-8 ml/kg/h. Infusion rate 8-12 ml/kg/h can potentially lead to dilutional coagulopathy and thus to increase the volume of blood loss. Infusion rate 4-6 ml/kg/h is associated with relative risk of hypovolemia and can't be recommended.

  20. 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

  1. 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

  2. Hepatic Microenvironment Affects Oval Cell Localization in Albumin-Urokinase-Type Plasminogen Activator Transgenic Mice

    PubMed Central

    Braun, Kristin M.; Thompson, Anne W.; Sandgren, Eric P.

    2003-01-01

    Mice carrying an albumin-urokinase type plasminogen activator transgene (AL-uPA) develop liver disease secondary to uPA expression in hepatocytes. Transgene-expressing parenchyma is replaced gradually by clones of cells that have deleted transgene DNA and therefore are not subject to uPA-mediated damage. Diseased liver displays several abnormalities, including hepatocyte vacuolation and changes in nonparenchymal tissue. The latter includes increases in laminin protein within parenchyma and the appearance of cytokeratin 19-positive bile ductule-like cells (oval cells) both in portal regions and extending into the hepatic parenchyma. In this study, we subjected AL-uPA mice to two-thirds partial hepatectomy to identify the response of these livers to additional growth stimulation. We observed several changes in hepatic morphology. First, the oval cells increased in number and often formed ductules in the parenchyma. Second, this cellular change was accompanied by a further increase in laminin associated with single or clusters of oval cells. Third, desmin-positive Ito cells increased in number and maintained close association with oval cells. Fourth, these changes were localized precisely to uPA-expressing areas of liver. Regenerating clones of uPA-deficient cells appeared to be unaffected both by stromal and cellular alterations. Thus, additional growth stimulation of diseased uPA-expressing liver induces an oval cell-like response, as observed in other models of severe hepatic injury, but the localization of this response seems to be highly regulated by the hepatic microenvironment. PMID:12507902

  3. 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

  4. Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus.

    PubMed

    Enocsson, Helena; Wetterö, Jonas; Skogh, Thomas; Sjöwall, Christopher

    2013-11-01

    Assessments of disease activity and organ damage in systemic lupus erythematosus (SLE) remain challenging because of the lack of reliable biomarkers and disease heterogeneity. Ongoing inflammation can be difficult to distinguish from permanent organ damage caused by previous flare-ups or medication side effects. Circulating soluble urokinase plasminogen activator receptor (suPAR) has emerged as a potential marker of inflammation and disease severity, and an outcome predictor in several disparate conditions. This study was done to evaluate suPAR as a marker of disease activity and organ damage in SLE. Sera from 100 healthy donors and 198 patients with SLE fulfilling the 1982 American College of Rheumatology classification criteria and/or the Fries criteria were analyzed for suPAR by enzyme immunoassay. Eighteen patients with varying degree of disease activity were monitored longitudinally. Disease activity was assessed by the SLE disease activity index 2000 and the physician's global assessment. Organ damage was evaluated by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Compared with healthy control subjects, serum suPAR levels were elevated significantly in patients with SLE. No association was recorded regarding suPAR levels and SLE disease activity in cross-sectional or consecutive samples. However, a strong association was observed between suPAR and SDI (P < 0.0005). Considering distinct SDI domains, renal, neuropsychiatric, ocular, skin, and peripheral vascular damage had a significant effect on suPAR levels. This study is the first to demonstrate an association between serum suPAR and irreversible organ damage in SLE. Further studies are warranted to evaluate suPAR and other biomarkers as predictors of evolving organ damage.

  5. Cell associated urokinase activity and colonic epithelial cells in health and disease.

    PubMed Central

    Gibson, P R; van de Pol, E; Doe, W F

    1991-01-01

    It is not known if urokinase-type plasminogen activator (uPA) is associated with normal colonic epithelial cells. The aims of this study were to determine if normal colonic epithelial cells have uPA activity and whether this is concentrated at the cell membrane. In addition, the contribution of colonic epithelial cell associated uPA activity to disease related pertubations of mucosal uPA activity were examined. A highly enriched population of colonic epithelial cells was isolated from resected colon or biopsy specimens by an enzymatic technique. uPA activity was measured in cell homogenates by a specific and sensitive colorimetric method and expressed relative to cellular DNA. In two experiments subcellular fractionation of colonic epithelial cells was performed by nitrogen cavitation followed by ultracentrifugation over a linear sucrose gradient. The fractions collected were analysed for uPA and organelle-specific enzyme activities. Normal colonic epithelial cells have cell associated uPA activity (mean (SEM) 5.6 (1.1) IU/mg, n = 18). This colocalised with fractions enriched for leucine-beta-naphthylamidase and 5'-nucleotidase, markers of plasma membrane. uPA activities in epithelial cells from cancerous colons (9.8 (3.1) n = 7) or from mucosa affected by inflammatory bowel disease (3.8 (0.7) n = 15) were not significantly different from normal (paired t test), while that in epithelial cells from greatly inflamed mucosa was similar to that from autologous normal or mildly inflamed areas (4.4 (1.2) v 5.9 (3.6), n = 9). Thus normal colonic epithelial cells have cell associated uPA activity which is concentrated on the plasma membranes, suggesting the presence of uPA receptors. Increased mucosal levels of uPA previously reported in patients with inflammatory bowel disease are not due to increased colonic epithelial cell associated uPA. PMID:1650741

  6. Soluble urokinase-type plasminogen activator receptor as a putative marker of male accessory gland inflammation.

    PubMed

    Autilio, C; Morelli, R; Milardi, D; Grande, G; Marana, R; Pontecorvi, A; Zuppi, C; Baroni, S

    2015-11-01

    The association between male accessory gland infection/inflammation (MAGI) and infertility is well-known in clinical practice. Standard semen analysis, leukocytospermia, and microbiological tests are often not enough accurate for a diagnosis. A large amount of biochemical parameters in seminal plasma have been suggested as inflammation markers, however, there is not yet a sensitive and specific biomarker that accurately identifies MAGI. We investigated the presence of soluble urokinase-type plasminogen activator receptor (suPAR), known marker of systemic inflammation, in the seminal plasma to evaluate its possible involvement in urogenital tract inflammation. On the basis of andrological evaluation, including spermiogram and ultrasound findings, we selected 76 patients with MAGI and 30 healthy men as control group. Patients were classified according to the results of the semen culture in group A (n = 28) presenting a bacterial MAGI and group B (n = 48) with abacterial MAGI. C-reactive protein (CRP), total protein (TP), procalcitonin (PCT), leukocytes peroxidase (LP), and suPAR concentrations were assayed on seminal plasma. Spermiogram parameters were significantly lower in the patients with MAGI than in controls. CRP, TP, PCT, and LP did not differ in MAGI vs. suPAR was detectable in all semen samples; it was significantly increased in A and B groups (86.6 ± 30.7 ng/mL vs. 39.7 ± 17.2 ng/mL) with an inverse correlation with sperm parameters. We selected by receiver operating characteristic curve a suPAR cut-off value of 55.3 ng/mL as a diagnostic threshold for the diagnosis of MAGI. We report in this study the first evidence of suPAR presence in seminal plasma, focusing on its interesting role as reliable and sensitive marker of inflammation for the differential diagnosis of MAGI. © 2015 American Society of Andrology and European Academy of Andrology.

  7. High molecular weight kininogen binds phosphatidylserine and opsonizes urokinase plasminogen activator receptor-mediated efferocytosis

    PubMed Central

    Yang, Aizhen; Dai, Jihong; Xie, Zhanli; Colman, Robert W.; Wu, Qingyu; Birge, Raymond B.; Wu, Yi

    2014-01-01

    Summary Phagocytosis of apoptotic cells (efferocytosis) is essential for regulation of immune responses and tissue homeostasis, and is mediated by phagocytic receptors. In this study we found that urokinase plasminogen activator receptor (uPAR) plays an important role in internalization of apoptotic cells, and also characterized the underlying mechanisms. In a flow cytometry-based phagocytic assay, uPAR-deficient (uPAR−/−) macrophages displayed significant defect in internalization but not tethering of apoptotic cells. When uPAR−/− mice were challenged with apoptotic cells, they exhibited pronounced splenomegaly resulting from accumulation of abundant apoptotic cells in spleen. Overexpression of uPAR in HEK-293 cells enhanced efferocytosis, which was inhibited by annexin V and phosphatidylserine (PS) liposome, suggesting that uPAR-mediated efferocytosis is dependent on PS. In serum lacking high-molecular-weight kininogen (HK), a uPAR ligand, uPAR-mediated efferocytosis was significantly attenuated, which was rescued by replenishment of HK. As detected by flow cytometry, HK selectively bound to apoptotic cells, but not viable cells. In purified systems, HK was specifically associated with PS liposome. HK binding to apoptotic cells induced its rapid cleavage to two-chain HKa and bradykinin. Both heavy chain and light chain of HKa were associated with PS liposome and apoptotic cells. HKa has higher binding affinity than HK to uPAR. Overexpression of Rac1/N17 cDNA inhibited uPAR-mediated efferocytosis. HK plus PS liposome stimulated a complex formation of CrkII with p130Cas and Dock-180, and Rac1 activation in uPAR-293 cells, but not in control HEK-293 cells. Thus, uPAR mediates efferocytosis through HK interaction with PS on apoptotic cells and activation of Rac1 pathway. PMID:24688027

  8. Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Patients With Schizophrenia

    PubMed Central

    Nielsen, Jimmi; Røge, Rasmus; Pristed, Sofie Gry; Viuff, Anne Grethe; Ullum, Henrik; Thørner, Lise Wegner; Werge, Thomas; Vang, Torkel

    2015-01-01

    Background: The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (suPAR) is a protein that can be measured in blood samples and reflects the levels of inflammatory activity. It has been associated with mortality and the development of type 2 diabetes and cardiovascular disease. Methods: suPAR levels in patients with schizophrenia were compared to healthy controls from the Danish Blood Donor Study. SuPAR levels were dichotomized at >4.0 ng/ml, which is considered the threshold for low grade inflammation. A multiple logistic regression model was used and adjusted for age, sex, and current smoking. Results: In total we included 1009 subjects, 105 cases with schizophrenia (10.4%) and 904 controls (89.6%). The mean suPAR values were 4.01 ng/ml (SD = 1.43) for the cases vs 1.91 ng/ml (SD = 1.35) for the controls (P < .001). Multiple logistic regression with odds ratio (OR) for suPAR levels >4.0 ng/ml yielded: schizophrenia, OR: 46.15 95% CI 22.69–93.87, P < .001; age, OR: 1.02 95% CI 0.99–1.02, P = .15; male sex, OR: 0.70 95% CI 0.35–1.36, P = .29; and current smoking, OR: 3.51 95% CI 1.78–6.94, P < .001. Conclusions: Patients with schizophrenia had significantly higher suPAR levels than healthy controls. Further studies are warranted to clarify if elevated suPAR levels are involved in the pathophysiology of schizophrenia and/or the increased mortality found in patients with schizophrenia. PMID:25154621

  9. Regulation of urokinase receptor proteolytic function by the tetraspanin CD82.

    PubMed

    Bass, Rosemary; Werner, Finn; Odintsova, Elena; Sugiura, Tsuyoshi; Berditchevski, Fedor; Ellis, Vincent

    2005-04-15

    The high affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored cellular receptor (uPAR) promotes plasminogen activation and the efficient generation of pericellular proteolytic activity. We demonstrate here that expression of the tetraspanin CD82/KAI1 (a tumor metastasis suppressor) leads to a profound effect on uPAR function. Pericellular plasminogen activation was reduced by approximately 50-fold in the presence of CD82, although levels of components of the plasminogen activation system were unchanged. uPAR was present on the cell surface and molecularly intact, but radioligand binding analysis with uPA and anti-uPAR antibodies revealed that it was in a previously undetected cryptic form unable to bind uPA. This was not due to direct interactions between uPAR and CD82, as they neither co-localized on the cell surface nor could be co-immunoprecipitated. However, expression of CD82 led to a redistribution of uPAR to focal adhesions, where it was shown by double immunofluorescence labeling to co-localize with the integrin alpha(5)beta(1), which was also redistributed in the presence of CD82. Co-immunoprecipitation experiments showed that, in the presence of CD82, uPAR preferentially formed stable associations with alpha(5)beta(1), but not with a variety of other integrins, including alpha(3)beta(1). These data suggest that CD82 inhibits the proteolytic function of uPAR indirectly, directing uPAR and alpha(5)beta(1) to focal adhesions and promoting their association with a resultant loss of uPA binding. This represents a novel mechanism whereby tetraspanins, integrins, and uPAR, systems involved in cell adhesion and migration, cooperate to regulate pericellular proteolytic activity and may suggest a mechanism for the tumor-suppressive effects of CD82/KAI1.

  10. Gelsolin Induces Colorectal Tumor Cell Invasion via Modulation of the Urokinase-Type Plasminogen Activator Cascade

    PubMed Central

    Zhuo, Jingli; Tan, Ee Hong; Yan, Benedict; Tochhawng, Lalchhandami; Jayapal, Manikandan; Koh, Shiuan; Tay, Hwee Kee; Maciver, Sutherland K.; Hooi, Shing Chuan; Salto-Tellez, Manuel; Kumar, Alan Prem; Goh, Yaw Chong; Lim, Yaw Chyn; Yap, Celestial T.

    2012-01-01

    Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells. We found that gelsolin was highly expressed at tumor borders infiltrating into adjacent liver tissues, as examined by immunohistochemistry. Although gelsolin contributes to lamellipodia formation in migrating cells, the mechanisms by which it induces tumor invasion are unclear. Gelsolin’s influence on the invasive activity of colorectal cancer cells was investigated using overexpression and small interfering RNA knockdown. We show that gelsolin is required for invasion of colorectal cancer cells through matrigel. Microarray analysis and quantitative PCR indicate that gelsolin overexpression induces the upregulation of invasion-promoting genes in colorectal cancer cells, including the matrix-degrading urokinase-type plasminogen activator (uPA). Conversely, gelsolin knockdown reduces uPA levels, as well as uPA secretion. The enhanced invasiveness of gelsolin-overexpressing cells was attenuated by treatment with function-blocking antibodies to either uPA or its receptor uPAR, indicating that uPA/uPAR activity is crucial for gelsolin-dependent invasion. In summary, our data reveals novel functions of gelsolin in colorectal tumor cell invasion through its modulation of the uPA/uPAR cascade, with potentially important roles in colorectal tumor dissemination to metastatic sites. PMID:22927998

  11. Serum cathepsin B and plasma urokinase-type plasminogen activator levels in gastrointestinal tract cancers.

    PubMed

    Herszényi, László; István, Gábor; Cardin, Romilda; De Paoli, Massimo; Plebani, Mario; Tulassay, Zsolt; Farinati, Fabio

    2008-10-01

    Cathepsin B (CATB) and urokinase-type plasminogen activator (UPA) play an important part in cancer invasion and metastasis. The behavior of CATB and UPA has not been evaluated in the same experimental setting in different gastrointestinal tumors and in precancerous lesions. Serum CATB and plasma UPA levels were determined by enzyme-linked immunoadsorbent assay and their sensitivity, specificity, and diagnostic accuracy have been calculated in patients with colorectal (n=72), gastric (n=30), hepatocellular (n=28), and pancreatic cancer (n=15) as well as in gastric epithelial dysplasia (n=25), colorectal adenomas (n=30), and tumor-free control patients (n=44). Serum CATB and plasma UPA antigen concentrations were significantly higher in patients with cancer than in controls. When all tumors were considered, the sensitivity, specificity, and diagnostic accuracy of CATB (89, 86, and 89%) were higher than that of UPA (76, 70, and 74%). CATB demonstrated in all types of tumors a better diagnostic accuracy than UPA. The positive predictive values of CATB (95%) and UPA (89%) may suggest their use in the evaluation of patients with a suspicion of malignancy. CATB and UPA were significantly higher in patients with gastric epithelial dysplasia and colorectal adenomas than in controls. Antigen levels of CATB and UPA were significantly correlated in both cancers and precancerous lesions. At the time of clinical presentation, serum CATB and plasma UPA antigen levels are sensitive indicators of gastrointestinal malignancies. Determination of serum CATB and plasma UPA levels may be useful to identify patients at a higher risk for progression to cancer, who could be subjected to a more strict follow-up protocol.

  12. Role of the urokinase-fibrinolytic system in epithelial-mesenchymal transition during lung injury.

    PubMed

    Marudamuthu, Amarnath Satheesh; Bhandary, Yashodhar Prabhakar; Shetty, Shwetha Kumari; Fu, Jian; Sathish, Venkatachalem; Prakash, Ys; Shetty, Sreerama

    2015-01-01

    Alveolar type II epithelial (ATII) cell injury precedes development of pulmonary fibrosis. Mice lacking urokinase-type plasminogen activator (uPA) are highly susceptible, whereas those deficient in plasminogen activator inhibitor (PAI-1) are resistant to lung injury and pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) has been considered, at least in part, as a source of myofibroblast formation during fibrogenesis. However, the contribution of altered expression of major components of the uPA system on ATII cell EMT during lung injury is not well understood. To investigate whether changes in uPA and PAI-1 by ATII cells contribute to EMT, ATII cells from patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, and mice with bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced lung injury were analyzed for uPA, PAI-1, and EMT markers. We found reduced expression of E-cadherin and zona occludens-1, whereas collagen-I and α-smooth muscle actin were increased in ATII cells isolated from injured lungs. These changes were associated with a parallel increase in PAI-1 and reduced uPA expression. Further, inhibition of Src kinase activity using caveolin-1 scaffolding domain peptide suppressed bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced EMT and restored uPA expression while suppressing PAI-1. These studies show that induction of PAI-1 and inhibition of uPA during fibrosing lung injury lead to EMT in ATII cells. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Role of the Urokinase-Fibrinolytic System in Epithelial–Mesenchymal Transition during Lung Injury

    PubMed Central

    Marudamuthu, Amarnath Satheesh; Bhandary, Yashodhar Prabhakar; Shetty, Shwetha Kumari; Fu, Jian; Sathish, Venkatachalem; Prakash, YS; Shetty, Sreerama

    2016-01-01

    Alveolar type II epithelial (ATII) cell injury precedes development of pulmonary fibrosis. Mice lacking urokinase-type plasminogen activator (uPA) are highly susceptible, whereas those deficient in plasminogen activator inhibitor (PAI-1) are resistant to lung injury and pulmonary fibrosis. Epithelial–mesenchymal transition (EMT) has been considered, at least in part, as a source of myofibroblast formation during fibrogenesis. However, the contribution of altered expression of major components of the uPA system on ATII cell EMT during lung injury is not well understood. To investigate whether changes in uPA and PAI-1 by ATII cells contribute to EMT, ATII cells from patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, and mice with bleomycin-, transforming growth factor β–, or passive cigarette smoke–induced lung injury were analyzed for uPA, PAI-1, and EMT markers. We found reduced expression of E-cadherin and zona occludens-1, whereas collagen-I and α-smooth muscle actin were increased in ATII cells isolated from injured lungs. These changes were associated with a parallel increase in PAI-1 and reduced uPA expression. Further, inhibition of Src kinase activity using caveolin-1 scaffolding domain peptide suppressed bleomycin-, transforming growth factor β–, or passive cigarette smoke–induced EMT and restored uPA expression while suppressing PAI-1. These studies show that induction of PAI-1 and inhibition of uPA during fibrosing lung injury lead to EMT in ATII cells. PMID:25447049

  14. 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.

  15. Uncharged isocoumarin-based inhibitors of urokinase-type plasminogen activator

    PubMed Central

    Heynekamp, Justin J; Hunsaker, Lucy A; Vander Jagt, Thomas A; Deck, Lorraine M; Vander Jagt, David L

    2006-01-01

    Background Urokinase-type plasminogen activator (uPA) plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis. Consequently, uPA is an attractive target for the development of small molecule active site inhibitors. Most of the recent drug development programs aimed at nonpeptidic inhibitors targeted at uPA have focused on arginino mimetics containing amidine or guanidine functional groups attached to aromatic or heterocyclic scaffolds. There is a general problem of limited bioavailability of these charged inhibitors. In the present study, uPA inhibitors were designed on an isocoumarin scaffold containing uncharged substituents. Results 4-Chloro-3-alkoxyisocoumarins were synthesized in which the 3-alkoxy group contained a terminal bromine; these were compared with similar inhibitors that contained a charged terminal functional group. Additional variations included functional groups attached to the seven position of the isocoumarin scaffold. N- [3-(3-Bromopropoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide was identified as an uncharged lead inhibitor of uPA, Ki = 0.034 μM. Molecular modeling of human uPA with these uncharged inhibitors suggests that the bromine occupies the same position as positively charged arginino mimetic groups. Conclusion This study demonstrates that potent uncharged inhibitors of uPA can be developed based upon the isocoumarin scaffold. A tethered bromine in the three position and an aromatic group in the seven position are important contributors to binding. Although the aim was to develop compounds that act as mechanism-based inactivators, these inhibitors are competitive reversible inhibitors. PMID:16466576

  16. Binding site of amiloride to urokinase plasminogen activator depends on species.

    PubMed

    Jankun, J; Skrzypczak-Jankun, E

    2001-10-01

    A novel drug candidate is checked on its potency on animal models before it can advance to human phase of the research. Usually negative results on animal phase disqualify it. Targeting specific enzymes by small chemicals raises the question about the appropriateness of this approach. As an example, the urokinase (uPA) is recognized as an important enzyme responsible for cancer metastasis and angiogenesis. It is therefore important to ask the question if a small chemical will inhibit uPA of different species with the same or different potency. Using DNA sequence and known structure of uPA we have modeled 3D structures of uPAs for several different species. By theoretical calculations we have determined most probable structure of amiloride/uPAs complexes. Catalytic triad (B57, B102, B195) and specificity pocket (B187-B197, B212-B229) are highly conserved in all cases, and are the regions responsible for proteolytic activity and recognition of the substrate. Significant differences were observed in a different region (loop B93-B101), that we identified as binding site of amiloride to the tissue plasminogen activator (tPA). Although tPA shares the same function of activating plasminogen and it is structurally similar to uPA. Amiloride is a specific inhibitor of uPA but does not inhibit tPA. Our study shows that predicted position of amiloride depends on species and in some cases was located, as expected, in the specificity pocket, but in the other cases close to the loop B93-B101. This location could weaken affinity of binding or prevent inhibition of uPA. Therefore, drug screening and elimination process based solely on animal study, without careful structural analysis, could lead to the elimination of potential drugs for humans.

  17. 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.

  18. Effects of small peptides or amino acids infused to a perfused area of the skin of Angora goats on mohair growth.

    PubMed

    Puchala, R; Pierzynowski, S G; Wuliji, T; Goetsch, A L; Sahlu, T; Lachica, M; Soto-Navarro, S A

    2002-04-01

    The effect of infusing dipeptides or their amino acids on mohair growth of Angora goats was investigated using a skin perfusion technique. Seven Angora wethers (average BW 24 +/- 2.5 kg) were implanted bilaterally with silicon catheters into the superficial branches of the deep circumflex iliac artery and vein and carotid artery. The experiment consisted of three 28-d phases. In the first 14 d of Phases 1 and 3, saline was infused into deep circumflex iliac arteries supplying skin and in Phase 2 a mixture of dipeptides (methionine-leucine [Met-Leu], lysine-leucine [Lys-Leu]) was infused into the artery on one side, and free amino acids were administered on the other side. Infusion rates of peptides were 0.85 mg/h Met-Leu and 0.85 mg/h Lys-Leu in 2.4 mL saline. Infusion rates of amino acids were 0.474 mg/h Lys, 0.483 mg/h Met, and 0.743 mg/h Leu in 2.4 mL saline. A 100-cm2 area within the perfused region was used to determine mohair growth. Two weeks after the cessation of infusions, perfused areas were shorn. Clean mohair production from the dipeptide- and amino acids-perfused regions were similar (4.21 vs 4.35 g/[100 cm2 +/- 28 d], respectively; P > 0.05). However, clean mohair production during dipeptides and amino acids infusions was greater (P < 0.01) than that observed during saline infusions (3.63 g/[100 cm2 +/- 28 d]). There were no significant differences between dipeptides and free amino acids in concentrations of various hormones and metabolites in blood from deep circumflex iliac veins (P > 0.05). In conclusion, the studied small dipeptides and amino acids similarly increased mohair fiber growth, presumably through supplying limiting amino acids directly to the fiber follicle.

  19. Intravenous infusion of amino acids in dogs attenuates hypothermia during anaesthesia and stimulates insulin secretion.

    PubMed

    Takashima, Satoshi; Shibata, Sanae; Yamada, Kazuto; Ogawa, Mizuho; Nishii, Naohito; Kitagawa, Hitoshi

    2016-07-01

    To evaluate the effect of intravenous infusion of amino acids on the prevention of hypothermia during anaesthesia in dogs. Randomized experimental trial. Seven healthy Beagle dogs. Four concentrations of amino acids were prepared with a 10% amino acid solution and an acetated Ringer's solution, and dogs were infused with each of the solutions at 1 week intervals. Dogs were infused with amino acid solution at 12 mL kg(-1)  hour(-1) for 60 minutes before and for 60 minutes after induction of anaesthesia. Acetated Ringer's solution was infused at the same rate for the remaining 60 minutes of anaesthesia. The infusion treatments were: 1) A0, nutrient-free acetated Ringer's solution; 2) A6, 0.6 g kg(-1)  hour(-1) ; 3) A9, 0.9 g kg(-1)  hour(-1) ; and 4) A12, 1.2 g kg(-1) hour(-1) . Rectal temperature (RT), heart rate (HR), mean arterial pressure (MAP), blood insulin, glucose, urea nitrogen (BUN) and creatinine concentrations, and time to extubation were measured. Before anaesthesia, RT was not affected by amino acid infusion. RT decreased progressively during anaesthesia and the absolute values of RT from 30 to 120 minutes were significantly higher in A12 than in A0 (p < 0.05). Reductions in HR and MAP during anaesthesia were attenuated by amino acid infusion in a dose-dependent manner. Plasma insulin concentration was significantly higher in A12 than in A0 during amino acid infusion and the increase in insulin concentration was greater during than before anaesthesia. BUN increased during amino acid infusion in a dose- and time-dependent fashion. Time until extubation was shorter in A12 than in A0. Amino acids infused at 1.2 g kg(-1)  hour(-1) in dogs attenuated the decrease in RT, HR, and MAP during anaesthesia, and induced a significant increase in plasma insulin concentration. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  20. The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations.

    PubMed

    Drinkwater, D C; Cushen, C K; Laks, H; Buckberg, G D

    1992-11-01

    The benefits of combined antegrade-retrograde infusion of blood cardioplegic solution are becoming well known in adult coronary and valvular heart operations. Many of these advantages relate directly to the pediatric patient. They include prompt arrest and even distribution, particularly with aortic insufficiency or open aortic root, avoiding or limiting ostial cannulation, allowing uninterrupted surgical procedures, and flushing air/debris from the coronary arteries. We therefore report on the first 123 pediatric patients at the University of California, Los Angeles, to receive myocardial protection with antegrade (aortic) infusion in conjunction with retrograde (coronary sinus) infusion of blood cardioplegic solution. We employed a retroplegia catheter with a self-inflating and deflating occlusion balloon on the tip of a pressure-monitored infusion cannula that remains in the coronary sinus during the operation. Induction blood cardioplegic solution, 30 ml/kg in equally divided doses, is administered in the coronary sinus first antegrade at an aortic pressure less than 80 mm Hg, followed by retrograde infusion at less than 40 mm Hg. Maintenance cardioplegic solution (15 ml/kg) is administered every 20 minutes through one or both of the infusion cannulas, depending on the surgical procedure. Patients' ages ranged from 1 week to 16 years with a mean of 4.6 years. The following procedures were included in descending order: Fontan 20, atrioventricular valve repair/replacement (and complete atrioventricular canal) 16, aortic root/Konno/Ross 16, Rastelli 13, aortic valve repair/replacement 13, ventricular septal defect (and double-outlet right ventricle) 13, tetralogy of Fallot 10, coronary artery reimplantation/fistula repair 6, truncus arteriosus 4, arterial switch 3, bidirectional Glenn 2, sinus venosus 2, and aortopulmonary window, Senning, Stansel, interrupted aortic arch, and Ebstein's, 1 each. Aortic crossclamp times ranged from 6 to 219 minutes with a mean of

  1. Overflow cascades on liquid-infused surfaces

    NASA Astrophysics Data System (ADS)

    Jacobi, Ian; Wexler, Jason; Stone, Howard

    2014-11-01

    The shear-driven dewetting of liquid-infused, micro-patterned surfaces is shown to exhibit a complex cascade of overflow, droplet generation and liquid displacement behaviors. Because liquid-infused surfaces are important in systems as varied as free-surface microfluidic devices and high Reynolds number drag-reducing coatings, understanding the dewetting mechanism is crucial to designing substrates capable of retaining infused liquid or, alternatively, dispensing it in a controlled way. Shear flow experiments on a variety of liquid-infused surface architectures are performed and the interfacial dynamics are characterized at macro- and microscopic scales. Analysis of the different stages of the dewetting cascade is then used to develop substrate design criteria for enhanced liquid control under a variety of shear flow conditions.

  2. [A new volumetric infusion pump (author's transl)].

    PubMed

    Radke, J; Wencker, K H

    1977-06-01

    Our experience with a new volumetric infusion pump "Tekmar T 92" is reported. Over a period of months the reported advantages of the instrument were investigated on three separate units. Some few disadvantages for routine use were observed.

  3. 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 ...

  4. [Iliac aneurysm rupture during preconditioning with levosimendan for coronary artery bypass graft].

    PubMed

    Román Fernández, A; López Álvarez, A; Corujeira Rivera, M C; Vilanova Vázquez, V; Carregal Rañó, A; Pereira Loureiro, M Á

    2014-03-01

    We present the case of a 77 year-old patient scheduled for coronary artery bypass. During the infusion of levosimendan as preconditioning for surgery, a rupture of right common iliac artery occurred. Surgery was delayed and an urgent aorto-bifemoral bypass was performed. We believe that the rupture of the artery was triggered by an increase in transmural pressure due to the inotropic effects of levosimendan in a dilated diseased vessel. To our knowledge, there are no cases of aneurysm rupture as a complication during levosimendan infusion, but the coincidence of events in time strongly suggests some kind of causal relationship.

  5. The History of Target-Controlled Infusion.

    PubMed

    Struys, Michel M R F; De Smet, Tom; Glen, John Iain B; Vereecke, Hugo E M; Absalom, Anthony R; Schnider, Thomas W

    2016-01-01

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted ("target") drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical and regulatory issues addressed in prototype development. We also describe the launch of the current clinically available systems.

  6. Improving Infusion Pump Safety Through Usability Testing.

    PubMed

    Miller, Kristen E; Arnold, Ryan; Capan, Muge; Campbell, Michele; Zern, Susan Coffey; Dressler, Robert; Duru, Ozioma O; Ebbert, Gwen; Jackson, Eric; Learish, John; Strauss, Danielle; Wu, Pan; Bennett, Dean A

    With the recognition that the introduction of new technology causes changes in workflow and may introduce new errors to the system, usability testing was performed to provide data on nursing practice and interaction with infusion pump technology. Usability testing provides the opportunity to detect and analyze potentially dangerous problems with the design of infusion pumps that could cause or allow avoidable errors. This work will reduce preventable harm through the optimization of health care delivery.

  7. 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.

  8. 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.

  9. Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin.

    PubMed Central

    Waltz, D A; Natkin, L R; Fujita, R M; Wei, Y; Chapman, H A

    1997-01-01

    The urokinase receptor (uPAR) coordinates plasmin-mediated cell-surface proteolysis and promotes cellular adhesion via a binding site for vitronectin on uPAR. Because vitronectin also binds plasminogen activator inhibitor type 1 (PAI-1), and plasmin cleavage of vitronectin reduces PAI-1 binding, we explored the effects of plasmin and PAI-1 on the interaction between uPAR and vitronectin. PAI-1 blocked cellular binding of and adhesion to vitronectin by over 80% (IC50 approximately 5 nM), promoted detachment of uPAR-bearing cells from vitronectin, and increased cellular migration on vitronectin. Limited cleavage of vitronectin by plasmin also abolished cellular binding and adhesion and induced cellular detachment. A series of peptides surrounding a plasmin cleavage site (arginine 361) near the carboxy-terminal end of vitronectin were synthesized. Two peptides spanning res 364-380 blocked binding of uPAR to vitronectin (IC50 approximately 8-25 microM) identifying this region as an important site of uPAR-vitronectin interaction. These data illuminate a complex regulatory scheme for uPAR-dependent cellular adhesion to vitronectin: Active urokinase promotes adhesion and also subsequent detachment through activation of plasmin or complex formation with PAI-1. Excess PAI-1 may also promote migration by blocking cellular adhesion and/or promoting detachment, possibly accounting in part for the strong correlation between PAI-1 expression and tumor cell metastasis. PMID:9202057

  10. 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.

  11. The effect of propofol infusion with topical epinephrine on cochlear blood flow and hearing: An experimental study.

    PubMed

    Jang, Chul Ho; Cho, Yong Beom; Lee, Jun Sik; Kim, Geun Hyung; Jung, Won-Kyo; Pak, Sok Cheon

    2016-12-01

    Propofol is the most commonly used intravenous (IV) anesthetic agent and is associated with hypotension upon induction of anesthesia. Intravenous propofol infusion has several properties that may be beneficial to patients undergoing middle ear surgery. Topical application of concentrated epinephrine is a valuable tool for achieving hemostasis in the middle ear and during mastoid surgery. The purpose of the present study was to determine the effects of propofol infusion with topical epinephrine on cochlear blood flow (CBF) and hearing in rats. Twenty one male Sprague-Dawley rats were divided into three groups. The rate of intravenous infusion of propofol was 4-6 ml/kg/hour. The first group (control group, n = 7) was given IV infusion of phosphate buffered saline (PBS) with topical application of PBS in the round window. In study group A (n = 7), the effect of topical phosphate buffered saline with IV infusion of propofol on CBF and hearing was evaluated. In study group B (n = 7), additional effects of topical epinephrine with IV infusion of propofol on CBF and hearing were evaluated. The laser Doppler blood flowmeter, CBF, and the mean arterial blood pressure (MAP) were measured and analyzed. Additionally, hearing test using auditory brainstem response (ABR) was performed in both groups. In both groups, infusion of propofol induced a time-dependent decrease in MAP. Approximately 30 min after the start of the propofol infusion, the CBF started to decrease slowly. The decrease in CBF was significantly greater in the study group compared to the control group. The threshold was elevated in the study group relative to the control group. During middle ear surgery, use of IV infusion of propofol with topical epinephrine cotton ball or cottonoid application is not recommended. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Disinhibition of AVP release during noradrenaline and angiotensin II infusions in dogs by maintaining normotension with sodium nitroprusside.

    PubMed

    Szczypaczewska, M; Simon, E; Simon-Oppermann, C; Gray, D A

    1993-05-01

    Noradrenaline (NA) and angiotensin II (A II) were infused intravenously in conscious dogs without (series I) and with (series II) additional infusions of sodium nitroprusside at doses re-establishing normal levels of mean arterial pressure (MAP). In series I, NA infusion (1.6 micrograms/min per kg for 30 min) initially elevated MAP by some 25 mm Hg and lowered heart rate by some 30 beats/min. Plasma concentrations of arginine vasopressin (AVP) remained constant, while those of A II and atrial natriuretic factor were slightly, but significantly, increased. Infusion of A II (10 or 20 ng/min per kg for 30 min) induced similar rises in MAP and slight reductions of heart rate and increased plasma AVP by 70% and atrial natriuretic factor by 60%. In series II, sodium nitroprusside (1-4 micrograms/min per kg) was added for 30 min to infusions of NE (1.6 micrograms/min per kg) and A II (20 ng/min per kg) in order to maintain MAP at its control level. This resulted in an 11-fold increase in plasma AVP during NA infusion and a 19-fold increase during A II infusion. Infusing sodium nitroprusside (4 micrograms/min per kg) alone lowered MAP to clearly hypotensive levels, but the resulting rises in plasma AVP were less than, rather than equal to, those seen at normotensive MAP levels during the combined infusions of sodium nitroprusside with A II or NA, respectively. It is concluded that both NA and A II exert strong stimulatory actions on AVP release which are, however, counteracted by inhibitory influences arising from the hypertensive effects of NA and A II.

  13. Myrtus communis L. infusions: the effect of infusion time on phytochemical composition, antioxidant, and antimicrobial activities.

    PubMed

    Messaoud, Chokri; Laabidi, Abdelmonoem; Boussaid, Mohamed

    2012-09-01

    In traditional medicine, myrtle (Myrtus communis L.) is frequently consumed as an infusion and decoction. In this study, we investigate the phenolic and volatile compositions and antioxidant and antibacterial activities of leaf infusions prepared during 3 different times. The total phenolics contents (146.74 to 179.55 mg GAE/g DM) varied significantly between infusions. Eleven phenolic compounds were identified by reversed-phase high-performance liquid chromatography. Phenolic acids (7.64 to 14.28 μmol/g DM) and flavonol glycosides (7.05 to 12.11 μmol/g DM) were the major phenolic fractions of infusions. Significant quantitative variation in 6 phenolic components was observed between infusions. Sixteen volatile components were identified by gas chromatography (GC) and GC mass spectrometry analyses. The main constituents were 1,8-cineole (42.58% to 51.39%), α-terpineol (9.45% to 9.72%), methyl eugenol (6.69% to 7.11%), and linalool (5.91% to 6.06%). Quantitative variations of the volatile components of the analyzed oils in relation to the infusion time were observed. The antioxidant properties of infusions, assayed through DPPH (2,2- diphenyl-1-picrylhydrazyl) method, β-carotene bleaching test, chelating effect on ferrous ions, and ferric reducing power method, were considerable and varied according to the infusion time. Myrtle infusions exhibited a substantial antimicrobial activity against 6 tested bacteria.