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Sample records for arterial infusion epirubicin

  1. [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.

  2. 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.

  3. Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: a review.

    PubMed

    Greidanus, J; Willemse, P H; Uges, D R; Oremus, E T; De Langen, Z J; De Vries, E G

    1988-12-09

    With the recent development of reliable portable pumps and safe venous access systems, continuous infusion of chemotherapeutic agents on an out-patient basis has become feasible. Advantages of continuous infusion are the long-term exposure of tumour cells to the drug and the fact that most toxic effects are reduced for doxorubicin, epirubicin and mitoxantrone due to elimination of the high peak plasma levels. Preliminary data for doxorubicin suggest that its antitumour activity is maintained. Pharmacokinetic studies with epirubicin and mitoxantrone showed a linear relationship between drug dose infused and the steady-state plasma level for these drugs. The area under the curve for leukocytes drug level was higher during continuous infusion than after an equitoxic bolus injection of epirubicin and mitoxantrone. Well-randomized clinical trials will be necessary to investigate the role of continuous infusion of antracyclines and mitoxantrone in cancer chemotherapy in the future.

  4. Hepatic uptake of epirubicin by isolated rat hepatocytes and its biliary excretion after intravenous infusion in rats.

    PubMed

    Shin, Dae Hwan; Park, Seong Hyeok; Jeong, Sung Woo; Park, Chun-Woong; Han, Kun; Chung, Youn Bok

    2014-12-01

    Anthracycline anticancer agents are widely used in the cancer chemotherapy for hepatocelluar carcinoma. However, accurate kinetic analyses of the hepatocellular uptake and efflux of the drugs have not been reported. We, therefore, investigated the hepatobiliary transport of epirubicin, an anthracycline derived antibiotic, after intravenous (i.v.) infusion in rats. The hepatic uptake mechanisms of epirubicin were also investigated in isolated rat hepatocytes. To analyze epirubicin levels in the biological samples, we used an HPLC-based method which has been validated for a kinetic study by suitable criteria. The uptake process of epirubicin by the hepatocytes revealed one saturable component, with a Km of 99.1 μg/mL and Vmax of 3.70 μg/min/10(6) cells. The initial uptake velocity of epirubicin was significantly inhibited in a temperature-dependent manner. The velocity was also reduced in the presence of metabolic inhibitors such as rotenone or carbonylcyanide-p-(trifluoromethoxy)-phenylhydrazone. Substrates for organic anion transporters such as bromosulfophthalein and taurocholate significantly inhibited the initial uptake velocity of epirubicin. We also attempted to determine the hepatobiliary transport of epirubicin after i.v. infusion in vivo. At steady-state after i.v. infusion of epirubicin (10-160 μg/min/kg), the drug was extensively accumulated in the liver, followed by excretion into bile. Furthermore, the CLbile,plasma and CLbile,liver decreased with a corresponding increase in the Css,plasma and Css,liver. In conclusion, present studies using isolated rat hepatocytes and in vivo i.v. infusion demonstrate that epirubicin is likely to be taken up into liver cells via organic anion transporting polypeptides, and that its biliary excretion might be mediated via specific transporters.

  5. 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

  6. A phase I and pharmacokinetic study with 21-day continuous infusion of epirubicin.

    PubMed

    de Vries, E G; Greidanus, J; Mulder, N H; Nieweg, M B; Postmus, P E; Schipper, D L; Sleijfer, D T; Uges, D R; Willemse, P H

    1987-09-01

    A phase I study with continuous administration of epirubicin for 21 days using a venous access port and a portable pump was performed. The first dose step was 2 mg/m2/d for 21 days. Interval between courses was 3 weeks. Dose increment per step was 1 mg/m2/d. Twenty-two patients entered the study and received a total of 58 courses with a median of two (range, one to nine). Up to 5 mg/m2/d no toxicity (according to World Health Organization [WHO] criteria) occurred. At 6 mg/m2/d (six pts), one patient had leukopenia grade 3. Two others had some hair loss. At 7 mg/m2/d (four patients), all patients developed mucositis (two grade 3). Three patients had bone marrow depression (one grade 3 anemia, one grade 4 leukocytopenia), and one patient developed the hand-foot syndrome. No other toxicity occurred in the patients. One patient obtained a partial response (18 weeks), ten had stable disease (12 to 54 weeks), seven had progressive disease, and four were not evaluable for response. One patient developed cellulitis around the port, responding to antibiotic treatment; one patient developed a vena cava superior syndrome that resolved with urokinase and removal of the access port. No septicemia occurred. Pharmacokinetic studies were performed by high-performance liquid chromatography (HPLC) with fluorometric detection. Plasma steady state was reached after 57 hours. During steady state there was a linear relationship between epirubicin dose administered and epirubicin level in plasma (r = .58, P less than .05), whole blood (r = .75, P less than .005), and in leukocytes (r = .68, P less than .05). The area under the curve in leukocytes was higher with continuous infusion of 6 mg/m2 for 21 days compared with bolus injection of 80 mg/m2. This method of continuous infusion with epirubicin may be a way to increase intracellular drug-uptake as expressed by intracellular area under curve (AUC). We recommend 6 mg/m2/d for 3 weeks for evaluation of antitumor efficacy in phase II

  7. [Evaluation of intraarterial 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

    2003-10-01

    We evaluated the effectiveness of FEM (5-FU, epirubicin, MMC) therapy. Data for 111 patients with liver metastasis from gastric cancer were collected from January 1977, until June 2003 (synchronous: 74 cases, asynchronous: 37 cases). Thirty patients were H1, 20 were H2 and 61 were classified as H3. The patients were divided into the following groups: Group A: Resection of the primary lesion and hepatic resection (n = 10), Group A1: Hepatic resection only (5 cases), Group A2: Hepatic resection and intraarterial infusion (5 cases). Group B: Resection of the primary lesion (n = 67), Group B1: Resection of the primary lesion only (46 cases), Group B2: Intraarterial infusion (21 cases). In Groups A2 and B2, FEM therapy was applied to A2a (4 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. 1-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. One case from Group A2a and 2 cases from Group B2a have survived for 3 years or longer. 1) We treated 3 patients with liver metastasis from gastric cancer who survived for 3 years or longer. 2) Resection of the primary lesion along with hepatic intraarterial infusion therapy (in addition to hepatic resection), especially in combination with FEM therapy, provided an extended length of survival.

  8. 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.

  9. Switching the Loaded Agent from Epirubicin to Cisplatin: Salvage Transcatheter Arterial Chemoembolization with Drug-eluting Microspheres for Unresectable Hepatocellular Carcinoma

    SciTech Connect

    Seki, Akihiko Hori, Shinich

    2012-06-15

    Purpose: There is no consensus on switching anticancer agents loaded onto drug carriers in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and clinical outcomes of TACE with cisplatin-loaded microspheres (CLM-TACE) in HCC patients refractory to TACE with epirubicin-loaded microspheres (ELM-TACE). Methods: Between February 2008 and June 2010, 85 patients with unresectable HCC refractory to ELM-TACE were enrolled to undergo CLM-TACE. The number of ELM-TACE sessions until judgment of resistance ranged from 1 to 4 (median, 2.1). CLM-TACE was performed using 50-100-{mu}m superabsorbent polymer microspheres loaded with 1 mg cisplatin/1 mg microspheres together with hepatic arterial infusion of 25 mg cisplatin and 500 mg 5-fluorouracil per patient. Tumor responses were evaluated by computed tomography according to the European Association for the Study of the Liver criteria. Results: The median number of CLM-TACE treatment sessions was 1.8 (range, 1-5), and the mean total dose of cisplatin per session was 42.8 mg (range, 30.0-59.0). After 6 months, 3 (3.5%) patients achieved complete response, 31 (36.5%) had partial response, 15 (17.6%) had stable disease, and 36 (42.4%) had progressive disease. The median overall survival and time to treatment failure after initial CLM-TACE were 13.3 and 7.2 months, respectively. Overall, 9.4% of patients experienced grade 3/4 adverse events. Conclusions: witching the loaded agent from epirubicin to cisplatin is a safe, well-tolerated, and efficacious treatment strategy for salvage TACE with drug-eluting microspheres in HCC patients refractory to ELM-TACE.

  10. Experimental embolization of rabbit renal arteries to compare the effects of poly L-lactic acid microspheres with and without epirubicin release against ntraarterial injection of epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-05-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with l m g of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI l.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemo-embolizing material, maintained high local concentrations of the

  11. Experimental Embolization of Rabbit Renal Arteries to Compare the Effects of Poly L-Lactic Acid Microspheres With and Without Epirubicin Release Against Intraarterial Injection of Epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-03-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with 1 mg of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI 1.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemoembolizing material, maintained high local concentrations of the

  12. Transcatheter Arterial Chemoembolization with Epirubicin-Loaded Superabsorbent Polymer Microspheres for 135 Hepatocellular Carcinoma Patients: Single-Center Experience

    SciTech Connect

    Seki, Akihiko Hori, Shinich; Kobayashi, Kazuya; Narumiya, Seizi

    2011-06-15

    Purpose: To evaluate the safety, clinical outcomes, and hepatic artery damage after transcatheter arterial chemoembolization (TACE) with epirubicin-loaded superabsorbent polymer microspheres (ELM-TACE) in patients with hepatocellular carcinoma (HCC) in a single center in Japan. Materials and Methods: This embolic agent is the original form of microspheres, which has the same composition and nature as HepaSpheres. Between May 2007 and June 2009, 135 patients with unresectable HCC who underwent ELM-TACE were enrolled. Embolization through extrahepatic collaterals was performed in 27 (20.0%) patients. Tumor response was evaluated using European Association for the Study of the Liver criteria at 1 and 6 months after initial ELM-TACE. Results: All procedures were successfully performed. The median number of TACE per patient was 1.7 sessions (range 1-5), and the mean epirubicin dose per session was 19.7 mg (range 2.0-60.0). Local pooling within target tumors was observed during TACE in 34 (25.2%) patients, and in 14 (10.4%) of the patients, gelatin sponge particles were added after the microspheres until each pooling disappeared. No serious adverse events associated with TACE occurred, and the incidence of postembolization syndrome was {<=}17.8%. The 1- and 6-month tumor response rates were 56.3 and 52.6%, respectively. The overall 1- and 2-year survival rates were 73.7 and 59.0%, respectively. Among 99 evaluated patients, 90 (90.9%) were found to have no hepatic artery damage after initial ELM-TACE. Conclusion: ELM-TACE is safe and effective treatment for unresectable HCC and is associated with low frequency of postembolization syndrome and minimal damage to the hepatic artery.

  13. Prospective Evaluation of Transcatheter Arterial Chemoembolization (TACE) with Multiple Anti-Cancer Drugs (Epirubicin, Cisplatin, Mitomycin C, 5-Fluorouracil) Compared with TACE with Epirubicin for Treatment of Hepatocellular Carcinoma

    SciTech Connect

    Sahara, Shinya; Kawai, Nobuyuki; Sato, Morio Tanaka, Takami; Ikoma, Akira; Nakata, Kouhei; Sanda, Hiroki; Minamiguchi, Hiroki; Nakai, Motoki; Shirai, Shintaro; Sonomura, Tetsuo

    2012-12-15

    Purpose: To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC). Materials and Methods: The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis; Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group. Results: No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019). Conclusion: TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone.

  14. Successful treatment of pulmonary artery sarcoma by a two-drug combination chemotherapy consisting of ifosfamide and epirubicin.

    PubMed

    Uchida, Akiko; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Yasushi; Kanehiro, Arihiko; Aoe, Motoi; Ohohara, Nobuya; Ueoka, Hiroshi; Tanimoto, Mitsune

    2005-07-01

    We describe a case of 63-year-old woman with pulmonary artery sarcoma successfully treated with chemotherapy. She developed acute shortness of breath, and left chest and shoulder pain. Although a diagnosis of acute pulmonary embolism was made at a local hospital and she received anticoagulation and thrombolysis therapy, no improvement was achieved. Thereafter, she underwent a pulmonary thromboectomy in our hospital, and the histological diagnosis was intimal sarcoma of the pulmonary artery. Since post-operative computed tomography (CT) scans of the chest showed obvious persistence of an intraluminal hypoattenuated area in the left main pulmonary artery, the patient was treated with four cycles of a doublet chemotherapy consisting of ifosfamide (2.5 g/m(2)/day) on days 1-5 and epirubicin (45 mg/m(2)/day) on days 2 and 3. CT scans of the chest after four cycles showed marked regression of the intraluminal hypoattenuated area in the left main pulmonary artery. This is the first case of pulmonary artery sarcoma responding to chemotherapy. Surgical resection is currently the most hopeful treatment for pulmonary artery sarcoma. However, intensive chemotherapy is worth trying in unresectable patients.

  15. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.

    PubMed

    Ross, P; Nicolson, M; Cunningham, D; Valle, J; Seymour, M; Harper, P; Price, T; Anderson, H; Iveson, T; Hickish, T; Lofts, F; Norman, A

    2002-04-15

    We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric cancer. Five hundred eighty patients with adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma were randomized to receive either ECF (epirubicin 50 mg/m(2) every 3 weeks, cisplatin 60 mg/m(2) every 3 weeks and PVI 5-FU 200 mg/m(2)/d) or MCF (mitomycin 7 mg/m(2) every 6 weeks, cisplatin 60 mg/m(2) every 3 weeks, and PVI 5-FU 300 mg/m(2)/d) and analyzed for survival, response, toxicity, and quality of life (QOL). The overall response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and 44.1% (95% CI, 38% to 50%) with MCF (P =.692). Toxicity was tolerable, and there were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade 2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema. Median survival was 9.4 months with ECF and 8.7 months with MCF (P =.315); at 1 year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF patients were alive. Median failure-free survival was 7 months with both regimens. Global QOL scores were better with ECF at 3 and 6 months. This study confirms response, survival, and QOL benefits of ECF observed in a previous randomized study. The equivalent efficacy of MCF was demonstrated, but QOL was superior with ECF. ECF remains one of the reference treatments for advanced esophagogastric cancer.

  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. 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.

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. [A patient with hepatic metastasis of breast cancer successfully treated with combined chemoendocrine therapy using epirubicin, tegafur and tamoxifen].

    PubMed

    Rai, Y; Emi, Y; Nishijima, N; Kai, S; Kano, T

    1999-09-01

    A solitary 1 cm sized metastatic lesion was found in the S5 region of the liver on a postoperative ultrasound screening of a 52-year-old breast cancer patient. It was confirmed by CT, MRI and hepatic angiography. At first, she was successfully treated with trans-arterial pirarubicin and lipiodol infusion but a metastatic lesion of similar size was found 6 months later in the same region. We then administered a triple 20 mg dose of epirubicin intravenously, and 450 mg of UFT and 30 mg of tamoxifen daily. Six months later the lesion had disappeared on US and CT scans and a complete remission has persisted for 18 months.

  8. 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.

  9. [Results of clinical study with epirubicin hydrochloride injectable solution in hepatoma].

    PubMed

    Monden, M; Nakamura, H; Yayoi, E; Monden, T; Ohi, H; Arisawa, J; Masuzawa, M; Shimizu, T; Tomono, N; Seki, K; Nakao, N; Todo, A; Inoue, Y; Sakon, M; Ohsaki, Y; Hosoki, T

    1998-09-01

    A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with hepatocellular carcinoma. Epirubicin-RTU 60 mg/m2 was injected into the hepatic artery and a three-week drug-free interval followed. Of 15 patients with hepatocellular carcinoma registered in this study, 14 patients were eligible, and they all completed the entire course. The objective was to investigate the safety of treatment with Epirubicin-RTU in 14 eligible patients. The adverse drug reactions frequently observed in these 14 eligible cases were leukopenia, neutropenia, thrombocytopenia, alopecia, and fever. They were all reversible and tolerable. With these results. Epirubicin-RTU was considered to be a safe pharmaceutical product to inject into the hepatic artery.

  10. [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.

  11. A case of hepatocellular carcinoma effectively treated with epirubicin aqueous vesicles in monodispersed iodized poppy-seed oil microdroplets.

    PubMed

    Higashi, S; Maeda, Y; Kai, M; Kitamura, T; Tsubouchi, H; Tamura, S; Setoguchi, T

    1996-01-01

    A 64-year-old woman with a solitary mass (18 mm in diameter) of hepatocellular carcinoma underwent hepatic arterial infusion therapy with water-in-oil-in-water emulsion (W/O/W) prepared by the membrane emulsification technique using a controlled pore glass membrane. In the W/O/W, numerous microdroplets of iodized poppy-seed oil (IPSO), which contained many vesicles of aqueous solution of epirubicin, were suspended in the external aqueous phase. The mean diameter of the IPSO microdroplets was 30 microns. Seventeen milliliters of the W/O/W containing 40 mg of epirubicin and 5 ml of IPSO was infused into the proper hepatic artery. No severe side effects were encountered. Computed tomography taken 3 days after the treatment revealed a clearly defined deposition of IPSO within the tumor. Serum alpha-fetoprotein levels, 5.35x10(3) ng/ml, before treatment, decreased to 131 ng/ml on 38 days after treatment. The tumor was extirpated and histopathological examination revealed complete necrosis of the tumor.

  12. 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.

  13. 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

  14. 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.

  15. Transarterial Chemoembolization With Cisplatin as Second-Line Treatment for Hepatocellular Carcinoma Unresponsive to Chemoembolization With Epirubicin-Lipiodol Emulsion

    SciTech Connect

    Maeda, Noboru Osuga, Keigo; Higashihara, Hiroki; Tomoda, Kaname; Mikami, Koji; Nakazawa, Tetsuro; Nakamura, Hironobu; Tomiyama, Noriyuki

    2012-02-15

    Purpose: The purpose of this retrospective study was to investigate the efficacy of transarterial chemoembolization (TACE) using cisplatin as a second-line treatment for advanced hepatocellular carcinoma (HCC) unresponsive to TACE using epirubicin-Lipiodol emulsion at our institution. Materials and Methods: Between January 2006 and March 2009, 51 patients with unresectable HCC underwent TACE using cisplatin. All patients had shown persistent viable tumor or tumor progression after at least 2 sessions of TACE using epirubicin-Lipiodol emulsion. TACE procedures consisted of arterial injection of a mixture of Lipiodol and cisplatin (30-100 mg [mean 57 {+-} 21]) (n = 29) or arterial infusion of cisplatin (30-100 mg [mean 87 {+-} 19]) solution (n = 22) followed by injection of 1-mm porous gelatin particles. Early tumor response was assessed by contrast-enhanced computed tomography (CT) according to Response Evaluation Criteria in Solid Tumors (RECIST) and European Association for the Study of the Liver (EASL) criteria. Overall survival and progression-free survival was calculated using the Kaplan-Meier method. Toxicity was assessed according to NCI-CTCAE version 3 criteria. Results: Response rates were 11.8 and 27.5% by RECIST and EASL criteria, respectively. Overall survival rates were 61.9, 48.2, and 28.9% at 1, 2, and 3 years, respectively, and the median survival time was 15.4 months. Progression-free survival rate was 35.2% at 1 year, and median progression-free survival time was 3.1 months. No major complications were observed, and the occurrence of postembolization syndrome was minimal. Grade 3 to 4 toxicities included thrombocytopenia (5.8%), increased aspartate aminotransferase (AST) level (35.3%), and increased alanine aminotransferase (ALT) level (23.5%). Conclusions: witching the TACE anticancer drug from epirubicin to cisplatin might be the feasible option for advanced HCC, even when considered resistant to the initial form of TACE.

  16. 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.

  17. 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.

  18. [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.

  19. Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

    PubMed

    Kawai, S; Tani, M; Okamura, J; Ogawa, M; Ohashi, Y; Monden, M; Hayashi, S; Inoue, J; Kawarada, Y; Kusano, M; Kubo, Y; Kuroda, C; Sakata, Y; Shimamura, Y; Jinno, K; Takahashi, A; Takayasu, K; Tamura, K; Nagasue, N; Nakanishi, Y; Makino, M; Masuzawa, M; Yumoto, Y; Mori, T; Oda, T

    1997-04-01

    A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

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

    SciTech Connect

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

    2009-05-15

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

  17. 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.

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

    PubMed Central

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

    2013-01-01

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

  19. 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.

  20. 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

  1. 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.

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

    SciTech Connect

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

    2007-04-15

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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. [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.

  18. Epirubicin

    MedlinePlus

    ... used in combination with other medications to treat breast cancer in patients who have had surgery to remove ... certain chemotherapy medications such as docetaxel (Taxotere) or paclitaxel (Abraxane, Onxol); or cimetidine (Tagamet). Your doctor may ...

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. [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.

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. [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.

  3. 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

  4. Dose-Dense Epirubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Chemotherapy in Node-Positive Breast Cancer

    PubMed Central

    Mirzaei, Hamid Reza; Sabet Rasekh, Parisa; Nasrollahi, Fatemeh; Sabet Rasekh, Parto; Akbari Tirabad, Zahra; Moein, Hamid Reza; Ghaffari Pour, Taban; Hajian, Parastoo

    2013-01-01

    Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement particularly in node-positive patients, but optimal dose and schedule remain undetermined. Objectives. This study aimed to assess the feasibility of dose-dense epirubicin and cyclophosphamide followed by docetaxel in node-positive breast cancer. Methods. All Patients first received 4 cycles of epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) at 2-week interval then followed by docetaxel (100 mg/m2) at 2-week interval for 4 cycles, with daily Pegfilgrastim (G-CSF) that was administered in all patients on days 3–10 after each cycle of epirubicin and cyclophosphamide infusion. Results. Fifty-eight patients with axillary lymph node-positive breast cancer were enrolled in the study, of whom 42 (72.4%) completed the regimen. There were two toxicity-related deaths, one patient due to grade 4 febrile neutropenia and the other due to congestive heart failure. Grade 3/4 neutropenia and febrile neutropenia were 13.8% and 5.1%. The most common grade 3/4 nonhematological complications were as follows: skin-nail disorders (48.3%), hand-foot syndrome (34.4%), paresthesia (38%), arthralgia (27.5%), and paresis (24.1%). Conclusions. Dose-dense epirubicin and cyclophosphamide followed by docetaxel with G-CSF support are not feasible, and it is not recommended for further investigation. PMID:24187626

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. Clinical pharmacokinetics of epirubicin: the importance of liver biochemistry tests.

    PubMed Central

    Twelves, C. J.; Dobbs, N. A.; Michael, Y.; Summers, L. A.; Gregory, W.; Harper, P. G.; Rubens, R. D.; Richards, M. A.

    1992-01-01

    The influence of liver biochemistry tests on epirubicin pharmacokinetics has been investigated in 52 women with advanced breast cancer, 27 of whom had radiologically proven liver metastases. Patients received epirubicin 12.5-120 mg m-2 given as an i.v. bolus. Epirubicin levels were measured by HPLC following the first cycle of treatment. Epirubicin elimination, expressed as clearance (dose/AUC), in the 22 patients with normal AST and bilirubin was compared with that of 30 patients with a raised AST +/- raised bilirubin. Epirubicin clearance was significantly reduced in the patients with a raised AST, whether their serum bilirubin was normal (22 patients) or elevated (eight patients). In the 30 patients with a raised AST +/- raised bilirubin, epirubicin clearance correlated strongly with the level of AST (r = -0.72) but not with serum bilirubin, alkaline phosphatase, albumin or creatinine. Using a multiple regression analysis, AST was the only one of these biochemical variables predictive of epirubicin clearance (r2 = 0.47, P = 0.0006). We conclude that a raised serum AST is a more sensitive and reliable measure of abnormal epirubicin pharmacokinetics than increased bilirubin. These findings have implications for anthracycline treatment in patients with abnormal liver biochemistry. PMID:1419619

  11. 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.

  12. 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.

  13. 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.

  14. NC-6300, an epirubicin-incorporating micelle, extends the antitumor effect and reduces the cardiotoxicity of epirubicin.

    PubMed

    Takahashi, Amane; Yamamoto, Yoshiyuki; Yasunaga, Masahiro; Koga, Yoshikatsu; Kuroda, Jun-ichiro; Takigahira, Misato; Harada, Mitsunori; Saito, Hiroyuki; Hayashi, Tatsuyuki; Kato, Yasuki; Kinoshita, Taira; Ohkohchi, Nobuhiro; Hyodo, Ichinosuke; Matsumura, Yasuhiro

    2013-07-01

    Epirubicin is widely used to treat various human tumors. However, it is difficult to achieve a sufficient antitumor effect because of dosage limitation to prevent cardiotoxicity. We hypothesized that epirubicin-incorporating micelle would reduce cardiotoxicity and improve the antitumor effect. NC-6300 comprises epirubicin covalently bound to PEG polyaspartate block copolymer through an acid-labile hydrazone bond. The conjugate forms a micellar structure of 40-80 nm in diameter in an aqueous milieu. NC-6300 (10, 15 mg/kg) and epirubicin (10 mg/kg) were given i.v. three times to mice bearing s.c. or liver xenograft of human hepatocellular carcinoma Hep3B cells. Cardiotoxicity was evaluated by echocardiography in C57BL/6 mice that were given NC-6300 (10 mg/kg) or epirubicin (10 mg/kg) in nine doses over 12 weeks. NC-6300 showed a significantly potent antitumor effect against Hep3B s.c. tumors compared with epirubicin. Moreover, NC-6300 also produced a significantly longer survival rate than epirubicin against the liver orthotopic tumor of Hep3B. With respect to cardiotoxicity, epirubicin-treated mice showed significant deteriorations in fractional shortening and ejection fraction. In contrast, cardiac functions of NC-6300 treated mice were no less well maintained than in control mice. This study warrants a clinical evaluation of NC-6300 in patients with hepatocellular carcinoma or other cancers. © 2013 Japanese Cancer Association.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. [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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study.

    PubMed

    Elling, D; Eggemann, H; Kümmel, S; Breitbach, P; Kohls, A; Morack, G; Schlosser, H; Krocker, J

    2003-06-01

    The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. 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

  1. A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy.

    PubMed

    Liu, Ching-Wen; Wu, Yu-Tse; Lin, Kai-Jen; Yu, Tsan-Jung; Kuo, Yu-Liang; Chang, Li-Ching

    2016-06-01

    This study aimed to examine the efficacy of epirubicin-loaded gelatin hydrogel (EPI-H) in the treatment of superficial urothelium carcinoma. Hydrogel was prepared by Schiff base-crosslinking of gelatin with glutaraldehyde. EPI-H exhibited high entrapment efficiency (59.87% ± 0.51%). EPI-H also increased epirubicin accumulation in AY-27 cells when compared with the effect of aqueous solutions of epirubicin (EPI-AQ); respective epirubicin-positive cell counts were 69.0% ± 7.6% and 38.3% ± 5.8%. EPI-H also exhibited greater cytotoxicity against AY-27 cells than that of EPI-AQ; IC50 values were 13.1 ± 1.1 and 7.5 ± 0.3 μg/mL, respectively. Cystometrograms showed that EPI-H reduced peak micturition, threshold pressures, and micturition duration, and that it increased bladder compliance more so than EPI-AQ. EPI-H enhanced epirubicin penetration into basal cells of urothelium in vivo, whereas EPI-AQ did so only to the umbrella cells. EPI-H inhibited tumor growth upon intravesical instillation to tumor-bearing bladder of F344 rats, inducing higher levels of caspase-3 expression than that observed with EPI-AQ treatment; the number of caspase-3 positive cells in treated urothelium carcinoma was 13.9% ± 4.0% (EPI-AQ) and 34.1% ± 1.0%, (EPI-H). EPI-H has value as an improved means to administer epirubicin in intravesical instillation treatments for bladder cancer.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. [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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. Ifosfamide, epirubicin and cisplatin (IEP): another active combination for small cell lung cancer (SCLC).

    PubMed

    Thongprasert, S; Jiamsriponges, K

    1993-10-01

    Sixty-four SCLC patients (44 males and 20 females, median age 60 years, median PS 60%) were treated with an IEP regimen. Forty-nine cases were evaluable, 35 cases were limited disease (LD) and 14 cases were extensive disease (ED). Treatment consisted of ifosfamide 1.5 g/m2 i.v. infusion for 4 h on days 1 and 2 with mesna uroprotection; epirubicin 60 mg/m2 i.v. on day 1; and cis-platin 60 mg/m2 i.v. infusion over 2 h on day 3; repeated treatment every 4 weeks. Eighty percent response rate (95% confidence limit = 66.75% to 93.25%) was seen in LD with 22.8% CR. In ED, total response rate was 85.7% (95% confidence limit = 67.36% to 104.04%) with 21.4% CR. One-year survival of LD was 45.5% and ED was 17.6%. Treatment toxicity was moderate. Most common toxic effects included alopecia, leukopenia (28.5% grade 3, 14.3% grade 4) nausea and vomiting (50% grade 2, 15% grade 3) and anemia (26.5% grade 3 and 4). Addition of thoracic radiotherapy after complete chemotherapy (only CR and PR in LD cases) was a good prognostic factor. These results suggest that IEP regimen is one of the active combination for SCLC. The dosage of IEP in this study caused moderate toxicity.

  17. 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.

  18. 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.

  19. 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.

  20. [Trans-Arterial Chemoembolization Therapy for Giant Cholangiocellular Carcinoma - A Single Case Report].

    PubMed

    Yamashiro, Keita; Hori, Astushi; Yuki, Takeo; Ohira, Ryosuke; Hori, Shinichi

    2016-11-01

    Here, we report a case of cholangiocellular carcinoma that was successfully treated with chemotherapy using a selective intra-arterial infusion technique. A 65-year-old man presented to our hospital to obtain a second opinion regarding his disease. The patient was diagnosed with cholangiocellular carcinoma. The giant tumor was located in the porta hepatis. Some small nodules that were considered to be metastatic lesions were also observed in the surroundingarea. The tumor was judged by the primary physician to be too large for surgical treatment. Consequently, it was decided to treat the patient with trans-arterial chemoembolization(TACE)by selectingintra -arterial infusion of 5-FU, epirubicin(EPI), and mitomycin C prior to EPI-loaded HepaSphere(super-absorbent polymer microsphere)embolization, combined with concurrent systemic gemcitabine chemotherapy. After 5 sessions of the above treatment, the primary lesion reduced dramatically in size. In addition, the levels of CEA and CA19-9 decreased from 34.2 to 2.6 ng/mL and 1,540 to 149 U/mL, respectively. Although the patient's initial life expectancy was only 3 to 6 months, his life expectancy was extended to as longas 26 months followingthe initiation of TACE. This case suggests that treatment with TACE together with systemic chemotherapy can be a powerful therapeutic option for patients with inoperable cholangiocellular carcinoma.

  1. Epirubicin and DTIC (EDIC) for advanced soft-tissue sarcomas.

    PubMed

    Lopez, M; Carpano, S; Di Lauro, L; Vici, P; Conti, E M

    1991-01-01

    Fifty-six patients with measurable advanced soft-tissue sarcomas were treated with epirubicin, 90 mg/m2 intravenously on day 1, and DTIC, 250 mg/m2 intravenously on days 1-5, with the entire regimen repeated every 3 weeks. The overall response rate in 52 evaluable patients was 48% with 9 complete remissions. Noncardiac toxicity was limited predominantly to vomiting, alopecia and myelosuppression. Laboratory evidence of cardiotoxicity [greater than or equal to 20% decrease in left-ventricular ejection fraction (LVEF) from the baseline value] was observed in 4 out of 39 patients who had at least two determinations of LVEF, at a median dose of 1,305 mg/m2. Two patients had clinical congestive heart failure at cumulative dose of 1,440 and 1,620 mg/m2. These findings suggest that the combination of epirubicin and DTIC is an active regimen in soft-tissue sarcomas, and provide further evidence that epirubicin is a doxorubicin analogue with reduced cardiac toxicity, but preserved efficacy in this disease.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Randomised trial of gemcitabine versus flec regimen given intra-arterially for patients with unresectable pancreatic cancer.

    PubMed

    Cantore, M; Fiorentini, G; Luppi, G; Rosati, G; Caudana, R; Piazza, E; Comella, G; Ceravolo, C; Miserocchi, L; Mambrini, A; Del Freo, A; Zamagni, D; Aitini, E; Marangolo, M

    2003-12-01

    Gemcitabine is considered the golden standard treatment for unresectable pancreatic adenocarcinoma. Intra-arte-rial drug administration had shown a deep rationale with some interesting results. In a multicenter phase III trial, we compared gemcitabine given weekly with a combination of 5-fluoruracil, leucovorin, epirubicin, carboplatin (FLEC) administered intra-arteriously as first-line therapy in unresectable pancreatic adenocarcinoma. Patients were randomly assigned to receive gemcitabine at a dose of 1,000 mg/m2 over 30 minutes intravenously weekly for 7 weeks, followed by 1 week of rest, then weekly for 3 weeks every 4 weeks or 5-fluoruracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2, carboplatin 300 mg/m2 infused bolus intra-arteriously at three-weekly interval for 3 times. The primary end point was overall survival, while time to treatment failure, response rate, clinical benefit response were secondary endpoints. Sixty-seven patients were randomly allocated gemcitabine and 71 were allocated FLEC intra-arterially. Patients treated with FLEC lived for significantly longer than patients on gemcitabine (p=.036). Survival at 1 year was increased from 21% in the gemcitabine group to 35% in the FLEC group. Median survival was 7.9 months in the FLEC group and 5.8 months in the gemcitabine group. Median time to treatment failure was longer with FLEC (5.3 vs 4.2 months for FLEC vs gemcitabine respectively; p=.013). Clinical benefit was similar in both groups (17.9% for gemcitabine and 26.7% for FLEC; p=NS). CT-scan partial response was similar in both group (5.9% for gemcitabine and 14% for FLEC; p=NS). Toxicity profiles were different. Compared with gemcitabine, FLEC regimen given intra-arteriously, improved survival in patient with unresectable pancreatic adenocarcinoma.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. [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.

  12. Optimizing anticancer drug treatment in pregnant cancer patients: pharmacokinetic analysis of gestation-induced changes for doxorubicin, epirubicin, docetaxel and paclitaxel.

    PubMed

    van Hasselt, J G C; van Calsteren, K; Heyns, L; Han, S; Mhallem Gziri, M; Schellens, J H M; Beijnen, J H; Huitema, A D R; Amant, F

    2014-10-01

    Pregnant patients with cancer are increasingly treated with anticancer drugs, although the specific impact of pregnancy-induced physiological changes on the pharmacokinetics (PK) of anticancer drugs and associated implications for optimal dose regimens remains unclear. Our objectives were to quantify changes in PK during pregnancy for four frequently used anticancer agents doxorubicin, epirubicin, docetaxel and paclitaxel, and to determine associated necessary dose adjustments. A pooled analysis of PK data was carried out for pregnant (Pr) and nonpregnant (NPr) patients for doxorubicin (n = 16 Pr/59 NPr), epirubicin (n = 14 Pr/57 NPr), docetaxel (n = 3 Pr/32 NPr) and paclitaxel (n = 5 Pr/105 NPr). Compartmental nonlinear mixed effect models were used to describe the PK and gestational effects. Subsequently, we derived optimized dose regimens aiming to match to the area under the concentration-time curve (AUC) in nonpregnant patients. The effect of pregnancy on volumes of distribution for doxorubicin, epirubicin, docetaxel and paclitaxel were estimated as fold-change of <1.32, <2.08, <1.37 and <4.21, respectively, with adequate precision [relative standard error (RSE) <37%]. For doxorubicin, no gestational effect could be estimated on clearance (CL). For epirubicin, docetaxel and paclitaxel, a fold-change of 1.1 (RSE 9%), 1.19 (RSE 7%) and 1.92 (RSE 21%) were, respectively, estimated on CL. Calculated dose adjustment requirements for doxorubicin, epirubicin, docetaxel and paclitaxel were +5.5%, +8.0%, +16.9% and +37.8%, respectively. Estimated changes in infusion duration were marginal (<4.2%) except for paclitaxel (-21.4%). Clinicians should be aware of a decrease in drug exposure during pregnancy and should not a priori reduce dose. The decrease in exposure was most apparent for docetaxel and paclitaxel which is supported by known physiological changes during pregnancy. The suggested dose adaptations should only be implemented after conduct of further confirmatory

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells

    PubMed Central

    Ahmad, Sheikh F.; Ansaria, Mushtaq A.; Nadeem, Ahmed; Al-Shabanah, Othman A.; Al-Harbi, Mohammed M.; Bakheet, Saleh A.

    2016-01-01

    Dexrazoxane has been approved to treat anthracycline-induced cardiomyopathy and extravasation. However, the effect of dexrazoxane on epirubicin-induced genetic alterations in germ cells has not yet been reported. Thus, the aim of this study was to determine whether dexrazoxane modulates epirubicin-induced genetic damage in the germ cells of male mice. Our results show that dexrazoxane was not genotoxic at the tested doses. Furthermore, it protected mouse germ cells against epirubicin-induced genetic alterations as detected by the reduction in disomic and diploid sperm, spermatogonial chromosomal aberrations, and abnormal sperm heads. The attenuating effect of dexrazoxane was greater at higher dose, indicating a dose-dependent effect. Moreover, sperm motility and count were ameliorated by dexrazoxane pretreatment. Epirubicin induced marked biochemical changes characteristic of oxidative DNA damage including elevated 8-hydroxy-2ʹ-deoxyguanosine levels and reduction in reduced glutathione. Pretreatment of mice with dexrazoxane before epirubicin challenge restored these altered endpoints. We conclude that dexrazoxane may efficiently mitigate the epirubicin insult in male germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and associated health risks. Thus, pretreating patients with dexrazoxane prior to epirubicin may efficiently preserve not only sperm quality but also prevent the transmission of genetic damage to future generations. PMID:27690233

  18. 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

  19. 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.

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

    PubMed Central

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

    2015-01-01

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

  1. Dexrazoxane mitigates epirubicin-induced genotoxicity in mice bone marrow cells.

    PubMed

    Attia, Sabry M; Ahmad, Sheikh F; Saquib, Quaiser; Harisa, Gamaleldin I; Al-Khedhairy, Abdulaziz A; Bakheet, Saleh A

    2016-03-01

    Dexrazoxane is the only clinically approved cardioprotectant against anthracyclines-induced cardiotoxicity. Thus, detailed evaluation of the genotoxic potential of dexrazoxane and anthracyclines combination is essential to provide more insights into genotoxic and anti-genotoxic alterations that may play a role in the development of the secondary malignancies after treatment with anthracyclines. Thus, our aim was to determine whether non-genotoxic doses of dexrazoxane in combination with the anthracycline, epirubicin can modulate epirubicin-induced genotoxicity and apoptosis in somatic cells. Bone marrow micronucleus test complemented with fluorescence in situ hybridization assay and comet assay were performed to assess the genotoxicity of dexrazoxane and/or epirubicin. Apoptosis was analysed by using the annexin V assay and the occurrence of the hypodiploid DNA content. Generation of reactive oxygen species was also assessed in bone marrow by using the oxidant-sensing fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate. Dexrazoxane was neither genotoxic nor apoptogenic in mice at a single dose of 75 or 150mg/kg. Moreover, it has been shown that dexrazoxane affords significant protection against epirubicin-induced genotoxicity and apoptosis in the bone marrow cells in a dose-dependent manner. Epirubicin induced marked generation of intracellular reactive oxygen species and prior administration of dexrazoxane ahead of epirubicin challenge ameliorated accumulation of these free radicals. It is thus concluded that dexrazoxane can be safely combined with epirubicin and that pre-treatment with dexrazoxane attenuates epirubicin-induced generation of reactive oxygen species and subsequent genotoxicity and apoptosis. Thus, epirubicin-induced genotoxicity can be effectively mitigated by using dexrazoxane.

  2. Weekly epirubicin for breast cancer with liver metastases and abnormal liver biochemistry.

    PubMed Central

    Twelves, C. J.; O'Reilly, S. M.; Coleman, R. E.; Richards, M. A.; Rubens, R. D.

    1989-01-01

    Thirty-six consecutive patients with breast cancer and liver metastases with abnormal liver biochemistry were treated with epirubicin 25 mg m-2 i.v. weekly. No dose modification was made for abnormal liver biochemistry, but dose intensity was adjusted by delaying treatment according to myelosuppression. The UICC overall response rate according to UICC criteria was 11/36 (30%) and median response duration was 27 weeks. Liver biochemistry improved in a further seven patients. Treatment was well tolerated. Epirubicin given in this way is effective in patients with breast cancer and liver metastases. An initial deterioration in liver biochemistry may occur before there is a response to epirubicin. PMID:2605102

  3. 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

  4. Stability study of epirubicin in NaCl 0.9% injection.

    PubMed

    Pujol, M; Muñoz, M; Prat, J; Girona, V; De Bolós, J

    1997-09-01

    To determine the stability of epirubicin in NaCl 0.9% injection under hospital storage conditions. NaCl 0.9% solution was added to epirubicin lyophilized powder to make a final concentration of 1 mg/mL to study the degradation kinetics and 2 mg/mL to study the stability in polypropylene syringes under hospital conditions. Physical chemistry laboratory, Unitat de Fisicoquímica, Universitat de Barcelona. Solutions of epirubicin at 2 mg/mL in NaCl 0.9% solutions stored in plastic syringes were studied under hospital conditions at room temperature (25 +/- 1 degrees C) and under refrigeration (4 +/- 1 degrees C) both protected from light and exposed to room light (approximately 50 lumens/m2). All samples were studied in triplicate and epirubicin concentrations were obtained periodically throughout each storage/time condition via a specific stability-indicating HPLC method. To determine the degradation kinetics, solutions of epirubicin in NaCl 0.9% at 1 mg/mL were stored at different temperatures (40, 50, and 60 degrees C) to obtain the rate degradation constant and the shelf life at room temperature and under refrigeration. The degradation of epirubicin in NaCl 0.9% solutions follows first-order kinetics. The shelf life was defined as the time by which the epirubicin concentration had decreased by 10% from the initial concentration. In this study, epirubicin was stable in NaCl 0.9% injection stored in polypropylene containers for all time periods and all conditions. That results in a shelf life of at least 14 and 180 days at 25 and 4 degrees C, respectively. The maximum decrease in epirubicin concentration observed at 25 degrees C and 14 days was 4%, and at 4 degrees C and 180 days was 8%. The predicted shelf life obtained from the Arrhenius equation was 72.9 +/- 0.2 and 3070 +/- 15 days at 25 and 4 degrees C, respectively, in both dark and illuminated conditions. Solutions of epirubicin in NaCl 0.9% at 2 mg/mL are chemically stable when they are stored in

  5. 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

  6. 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

  7. 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

  8. [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.

  9. 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

  10. 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

  11. A phase I study of ixabepilone in combination with epirubicin in patients with metastatic breast cancer.

    PubMed

    Roché, Henri; De Benedictis, Elena; Cottura, Ewa; Govi, Silvia; Dalenc, Florence; Locatelli, Alberta; Deslandres, Marion; Zambetti, Milvia; Gladieff, Laurence; Messina, Marianne; Gianni, Luca

    2012-06-01

    In this phase I trial, 42 women with metastatic breast cancer were treated with a fixed dose of epirubicin (75 mg/m2) and escalating doses of ixabepilone (25, 30, and 35 mg/m2). The maximum-tolerated dose of ixabepilone in combination with epirubicin was 30 mg/m2 (the recommended dose for phase II evaluation), and the dose-limiting toxicity dose was 35 mg/m2 with grade 4 neutropenia. The objectives of this phase I trial were to determine the maximum-tolerated dose (MTD), toxicity profile, dose-limiting toxicities (DLT), pharmacokinetics, and the recommended phase II dose for ixabepilone in combination with epirubicin in women with metastatic breast cancer. Patients ≥18 years old with an histologically or cytologically confirmed diagnosis of invasive breast cancer and clinical evidence of locally recurrent or metastatic disease were enrolled and treated with a fixed dose of epirubicin (75 mg/m(2)) and escalating doses of ixabepilone (25, 30, and 35 mg/m(2)). Forty-two women were treated at 3 different dose levels of ixabepilone: 25 (n = 6), 30 (n = 30), and 35 mg/m(2) (n = 6) in combination with 75 mg/m(2) epirubicin. The MTD of ixabepilone in combination with epirubicin 75 mg/m(2) was 30 mg/m(2), and the DLT dose was 35 mg/m(2) with grade 4 neutropenia. Grade 3/4 neutropenia was the most frequent moderate-to-severe adverse event and was manageable and reversible. No deaths were reported. Objective responses were achieved in 18 of 32 patients with measurable disease (56% [90% CI, 40%-71%]) and in 9 of 22 evaluable patients treated at the MTD (41% [90% CI, 23%-61%]). Ixabepilone clearance and the epirubicin pharmacokinetic profile were similar across ixabepilone dose levels. The combination of ixabepilone and epirubicin was clinically active. The recommended dose for evaluation in phase II is epirubicin 75 mg/m(2), followed by ixabepilone 30 mg/m(2) every 3 weeks. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Human cytosolic sulfotransferase SULT1C4 mediates the sulfation of doxorubicin and epirubicin.

    PubMed

    Luo, Lijun; Zhou, Chunyang; Hui, Ying; Kurogi, Katsuhisa; Sakakibara, Yoichi; Suiko, Masahito; Liu, Ming-Cheh

    2016-04-01

    Doxorubicin, an anthracycline, has been reported to be excreted in sulfate conjugated form. The current study aimed to identify the human cytosolic sulfotransferase(s) (SULT(s)) that is(are) capable of sulfating doxorubicin and its analog epirubicin, and to verify whether sulfation of doxorubicin and epirubicin may occur under metabolic conditions. A systematic analysis of thirteen known human SULTs, previously cloned, expressed, and purified, revealed SULT1C4 as the only human SULT capable of sulfating doxorubicin and epirubicin. Cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells were labeled with [(35)S]sulfate in the presence of different concentrations of doxorubicin or epirubicin. Analysis of spent labeling media showed the generation and release of [(35)S]sulfated doxorubicin and epirubicin by HepG2 cells and Caco-2 cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the expression of SULT1C4 in both HepG2 cells and Caco-2 cells. These results provided a molecular basis underlying the previous finding that sulfate-conjugated doxorubicin was excreted in the urine of patients treated with doxorubicin. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  13. ATM and p53 regulate FOXM1 expression via E2F in breast cancer epirubicin treatment and resistance.

    PubMed

    Millour, Julie; de Olano, Natalia; Horimoto, Yoshiya; Monteiro, Lara J; Langer, Julia K; Aligue, Rosa; Hajji, Nabil; Lam, Eric W F

    2011-06-01

    In this report, we investigated the role and regulation of forkhead box M1 (FOXM1) in breast cancer and epirubicin resistance. We generated epirubicin-resistant MCF-7 breast carcinoma (MCF-7-EPI(R)) cells and found FOXM1 protein levels to be higher in MCF-7-EPI(R) than in MCF-7 cells and that FOXM1 expression is downregulated by epirubicin in MCF-7 but not in MCF-7-EPI(R) cells. We also established that there is a loss of p53 function in MCF-7-EPI(R) cells and that epirubicin represses FOXM1 expression at transcription and gene promoter levels through activation of p53 and repression of E2F activity in MCF-7 cells. Using p53(-/-) mouse embryo fibroblasts, we showed that p53 is important for epirubicin sensitivity. Moreover, transient promoter transfection assays showed that epirubicin and its cellular effectors p53 and E2F1 modulate FOXM1 transcription through an E2F-binding site located within the proximal promoter region. Chromatin immunoprecipitation analysis also revealed that epirubicin treatment increases pRB (retinoblastoma protein) and decreases E2F1 recruitment to the FOXM1 promoter region containing the E2F site. We also found ataxia-telangiectasia mutated (ATM) protein and mRNA to be overexpressed in the resistant MCF-7-EPI(R) cells compared with MCF-7 cells and that epirubicin could activate ATM to promote E2F activity and FOXM1 expression. Furthermore, inhibition of ATM in U2OS cells with caffeine or depletion of ATM in MCF-7-EPI(R) with short interfering RNAs can resensitize these resistant cells to epirubicin, resulting in downregulation of E2F1 and FOXM1 expression and cell death. In summary, our data show that ATM and p53 coordinately regulate FOXM1 via E2F to modulate epirubicin response and resistance in breast cancer.

  14. Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions.

    PubMed

    Loers, Gabriele; Saini, Vedangana; Mishra, Bibhudatta; Gul, Sheraz; Chaudhury, Sidhartha; Wallqvist, Anders; Kaur, Gurcharan; Schachner, Melitta

    2016-01-01

    Polysialic acid (PSA), a large, linear glycan composed of 8 to over 100 α2,8-linked sialic acid residues, modulates development of the nervous system by enhancing cell migration, axon pathfinding, and synaptic targeting and by regulating differentiation of progenitor cells. PSA also functions in developing and adult immune systems and is a signature of many cancers. In this study we identified vinorelbine, a semi-synthetic third generation vinca alkaloid, and epirubicin, an anthracycline and 4'-epimer of doxorubicin, as PSA mimetics. Similar to PSA, vinorelbine and epirubicin bind to the PSA-specific monoclonal antibody 735 and compete with the bacterial analog of PSA, colominic acid in binding to monoclonal antibody 735. Vinorelbine and epirubicin stimulate neurite outgrowth of cerebellar neurons via the neural cell adhesion molecule, via myristoylated alanine-rich C kinase substrate, and via fibroblast growth factor receptor, signaling through Erk pathways. Furthermore, the two compounds enhance process formation of Schwann cells and migration of cerebellar neurons in culture, and reduce migration of astrocytes after injury. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds vinorelbine and epirubicin, thus raising the possibility to re-target drugs used in treatment of cancers to nervous system repair. Vinorelbine and epirubicin, identified as PSA mimetics, enhance, like PSA, neuronal migration, neuritogenesis, and formation of Schwann cell processes, and reduce astrocytic migration. Ablating NCAM, inhibiting fibroblast growth factor (FGFR) receptor, or adding the effector domain of myristoylated alanine-rich C kinase substrate (MARCKS) minimize the vinorelbine and epirubicin effects, indicating that they are true PSA mimetics triggering PSA-mediated functions.

  15. Breast tumour growth inhibition in vitro through the combination of cyclophosphamide/metotrexate/5-fluorouracil, epirubicin/cyclophosphamide, epirubicin/paclitaxel, and epirubicin/docetaxel with the bisphosphonates ibandronate and zoledronic acid.

    PubMed

    Vogt, Ulf; Bielawski, Krzysztof P; Bosse, Ulrich; Schlotter, Claus M

    2004-11-01

    Breast cancer has a significant capacity to metastasize to bone. Bisphosphonates are the standard treatment for hypocalcaemia of malignancy (HCM), which is a common complication of bone metastasis. The combination of bisphosphonates with standard anticancer drugs such as paclitaxel or tamoxifen results in a synergistic apoptotic effect greater than that produced by either single agent alone. Potential antitumour effects in vitro of the two bisphosphonates zoledronic acid (Zol) and ibandronate (Ib) (each at 30 microM) combined with different anticancer drug combinations: cyclophosphamide/metotrexate/5-fluorouracil (CMF), epirubicin/cyclophosphamide (EC), epirubicin/paclitaxel (ET), and epirubicin/docetaxel (EDoc) were investigated using ATP-cell viability assay (ATP-CVA). Twenty cases of female primary, invasive breast cancer were assessed. Ibandronate and zoledronic acid alone showed an inhibitory effect on breast cancer tumour cells in vitro. The breast tumour growth inhibition effect for those two drugs amounted to 22 and 25% respectively. Inhibitory effects were clearly visible for all four combinations of anticancer drugs together with both bisphosphonates. Combinations of anticancer drugs with zoledronic acid seem to be more effective with respect to tumour growth inhibition than combinations with ibandronate.

  16. [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.

  17. 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.

  18. [Results of clinical study with epirubicin hydrochloride injectable solution and cyclophosphamide in breast cancer].

    PubMed

    Koyama, H; Adachi, I; Tajima, T; Kanda, K; Yoshida, M; Miura, S; Nakao, K; Kikkawa, N; Takai, S; Toge, T; Tamura, K; Inaji, H; Shiba, E

    1998-09-01

    A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with breast cancer. One course of treatment consisted of one intravenous administration of Epirubicin-RTU at the dose of 60 mg/m2 followed by a 3-week drug-free interval and concomitant daily administration of oral cyclophosphamide at 100 mg/day during the period between Days 1 through 14. At least, two courses of treatment were given. Among 20 registered cases, all 20 cases were eligible and 16 cases completed the whole course of the study. In 16 completers, PR was observed in 5 cases, indicating the efficacy rate of 31.3% (5/16).. No local irritation was observed at the injection sites. Adverse reactions frequently observed were leukopenia, neutropenia, anorexia, alopecia, and nausea/vomiting, which were all reversible and tolerable. From the above results, Adverse reactions both locally and systemically were tolerable. Intravenous administration of Epirubicin-RTU was considered to be useful for the treatment of breast cancer.

  19. Vinorelbine and epirubicin share common features with polysialic acid and modulate neuronal and glial functions

    PubMed Central

    Mishra, Bibhudatta; Gul, Sheraz; Chaudhury, Sidhartha; Wallqvist, Anders; Kaur, Gurcharan; Schachner, Melitta

    2015-01-01

    Polysialic acid (PSA), a large, linear glycan composed of 8 to over 100 α2,8-linked sialic acid residues, modulates development of the nervous system by enhancing cell migration, axon pathfinding, synaptic targeting and by regulating differentiation of progenitor cells. PSA also functions in developing and adult immune systems and is a signature of many cancers. In this study we identified vinorelbine, a semi-synthetic third generation vinca alkaloid, and epirubicin, an anthracycline and 4′-epimer of doxorubicin, as PSA mimetics. Similar to PSA, vinorelbine and epirubicin bind to the PSA-specific monoclonal antibody 735 and compete with the bacterial analogue of PSA, colominic acid in binding to monoclonal antibody 735. Vinorelbine and epirubicin stimulate neurite outgrowth of cerebellar neurons via the neural cell adhesion molecule (NCAM), via myristoylated alanine-rich C kinase substrate, and via fibroblast growth factor receptor, signaling through Erk pathways. Furthermore, the two compounds enhance process formation of Schwann cells and migration of cerebellar neurons in culture, and reduce migration of astrocytes after injury. These novel results show that the structure and function of PSA can be mimicked by the small organic compounds vinorelbine and epirubicin, thus raising the possibility to retarget drugs used in treatment of cancers to nervous system repair. PMID:26443186

  20. A first-in-human Phase 1 study of epirubicin-conjugated polymer micelles (K-912/NC-6300) in patients with advanced or recurrent solid tumors.

    PubMed

    Mukai, Hirofumi; Kogawa, Takahiro; Matsubara, Nobuaki; Naito, Yoichi; Sasaki, Masaoki; Hosono, Ako

    2017-06-01

    Background K-912 also known as NC-6300 is a novel epirubicin pro-drug conjugate developed using micellar nanoparticle technology. We conducted a first-in-human, Phase 1, open-label, non-randomized dose escalation study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of K-912 administered as monotherapy in patients with advanced or recurrent solid tumors. Methods Patients aged 41 to 72 years with histologically or cytologically confirmed advanced or recurrent malignant solid tumors either refractory to standard therapy or had no other viable treatment options were enrolled. K-912 was administered as a 10-min intravenous infusion every three weeks. Doses were increased in a step-wise manner based on a predetermined series: 15, 30, 60, 80, 100, 130, 170, and 225 mg/m(2). The appropriateness of doses above 60 mg/m(2) was assessed using a Bayesian continual reassessment model. Treatment-emergent adverse events and tumor response were evaluated according to internationally accepted criteria. Results Nineteen patients were treated with K-912. No additional adverse events expected with anthracyclines were observed. While the number of patients treated at the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) were small, MTD and RP2D were established to be 170 mg/m(2). Partial response was observed in one patient with breast cancer treated at 100 mg/m(2), yielding an objective response rate of 5% (1/19). Stable disease was observed in 10 patients. The human pharmacokinetic profile of K-912 was consistent with that observed from nonclinical studies in rats and monkeys. Conclusions This study showed that K-912 was well tolerated in patients with various solid tumors and exhibited less toxicity than conventional epirubicin formulations.

  1. [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.

  2. Advanced chemoresistant breast cancer responding to multidisciplinary treatment with hyperthermia, radiotherapy, and intraarterial infusion.

    PubMed

    Yokoyama, Goro; Fujii, Teruhiko; Ogo, Etsuyo; Yanaga, Hiroshi; Toh, Uhi; Yamaguchi, Miki; Mishima, Mai; Takamori, Shinzo; Shirouzu, Kazuo; Yamana, Hideaki

    2005-04-01

    We employed multidisciplinary therapy, consisting of hyperthermia, radiotherapy, and intraarterial infusion, for a patient with progressive advanced breast cancer that was resistant to epirubicin hydrochloride and cyclophosphamide (EC) therapy as well as being resistant to docetaxel hydrate, and obtained a good therapeutic response. Because estrogen and progesterone receptors were both negative and HER2 was 3(+), administration of trastuzumab was started, and this patient has shown no signs of recurrence at 33 months after our treatment. The results suggested that our multidisciplinary therapy can be an effective method for the treatment of progressive breast cancer showing resistance to major chemotherapy agents such as anthracyclines and taxanes.

  3. 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.

  4. 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

  5. Infusional fluorouracil, epirubicin, and cisplatin followed by weekly paclitaxel plus bevacizumab in locally advanced breast cancer with unfavorable prognostic features.

    PubMed

    Balduzzi, Alessandra; Montagna, Emilia; Bagnardi, Vincenzo; Torrisi, Rosalba; Bertolini, Francesco; Mancuso, Patrizia; Scarano, Eloise; Viale, Giuseppe; Veronesi, Paolo; Cardillo, Anna; Orlando, Laura; Goldhirsch, Aron; Colleoni, Marco

    2009-03-01

    The objective of this study was to evaluate the clinical and biological activities of bevacizumab in combination with preoperative anthracyclines and taxane-based chemotherapy in locally advanced breast cancer selected for unfavorable prognostic features. Patients with cT2-4c, cN0-2, estrogen and progesterone receptors less than 10% of the cells or cT4d and any estrogen/progesterone receptors expression received four courses of ECF-chemotherapy (epirubicin, cisplatin, fluorouracil as continuous infusion) followed by three courses of weekly paclitaxel in combination with bevacizumab. Thirty patients were included in the study. An objective response, either complete or partial, was observed in 26 patients (87%; 95% confidence interval: 69-96%), stable disease was observed in two patients (7%), and two patients (7%) progressed. A pathological complete response was obtained in 10 patients (33%; 95% confidence interval: 17-53%). Side effects related to bevacizumab with grade >or=2 included headache and hypertension. A nonstatistical significant decrease in the median value of circulating endothelial cells was observed at surgery (3.0/microl vs. 5.7/microl, P=0.19). In conclusion, high rates of both clinical and pathological responses with anthracycline-containing chemotherapy followed by weekly paclitaxel plus bevacizumab were observed in locally advanced breast cancer with unfavorable prognostic features. A non-negligible rate of progressive disease was observed, suggesting careful monitoring of the patients. Further studies evaluating the potential benefit of bevacizumab in neoadjuvant treatment need to be tested.

  6. 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.

  7. Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations.

    PubMed

    Tariq, Mohammad; Alam, Md Aftab; Singh, Anu T; Panda, Amulya K; Talegaonkar, Sushama

    2016-10-01

    Epirubicin (EPI) elicits poor-oral bioavailability hence commercially available as injection for intravenous administration which follows a rapid increase and fast decay in plasma drug concentration often needs a frequent dosing that may lead to serious side effects. Aim of the present study is to develop a nanoparticulate system which could deliver epirubicin effectively via oral administration and could eventually promote new concept "chemotherapy at home." In this perspective, epirubicin loaded Poly-lactide-co-glycolic acid nanoparticles (EPI-NPs) were developed by double emulsion evaporation techniques and evaluated for its safety and efficacy against Ehrlich's Ascites (EAT) induced tumor in balb/c mice. In vivo fate of nanoparticles after oral administration in Albino wistar rats was also studied. EPI-NPs showed marked reduction in tumor size ∼40% while tumor size was increased 3.55 and 3.28 folds in control as well as in group treated orally with free epirubicin solution (EPI-S), respectively. Furthermore, toxicological evaluation demonstrated insignificant difference in levels of biomarkers including MDA, CAT, SOD, LDH, CK-MB, AST and ALT when EPI-NPs-oral treatment was compared with control group while levels of these biomarkers were found extremely significant in group treated with EPI-S (i.v). and demonstrated increment in LDH (p < 0.001), CK-MB (p < 0.001), AST (p < 0.001), ALT (p < 0.001) and MDA levels (p < 0.001) and reduction in SOD (p < 0.001) and CAT levels (p < 0.001) thus confirmed better safety profile of EPI-NPs oral than EPI-S i.v. Biodistribution study demonstrated the presence of NPs in different body organs and blood which suggests probability of NPs translocation across intestine thus at the tumor site.

  8. What is the effect of adjusting epirubicin doses for body surface area?

    PubMed Central

    Dobbs, N. A.; Twelves, C. J.

    1998-01-01

    Doses of cytotoxic drugs are routinely adjusted according to body surface area. We have evaluated this practice in 32 women with advanced breast cancer treated with single-agent epirubicin 12.5-120 mg m(-2). Epirubicin and its metabolites were measured by high-performance liquid chromatography (HPLC). Unadjusted plasma clearance was calculated from dose in mg, and adjusted clearance from dose in mg m(-2). Unadjusted clearance did not correlate with surface area, height, weight, per cent ideal body weight or body mass index. There was no difference in the coefficient of variation (CV) of adjusted and unadjusted clearance (39.4% and 37.7% respectively). The AUC that would have resulted from giving an unadjusted dose was calculated. This predicted AUC was accurate, unbiased and had the same CV as the actual AUC. Similarly, in 11 patients an analysis of actual and predicted neutropenia confirmed that unadjusted dosing would have had no significant effect on the pattern of myelosuppression. Normalization of epirubicin dosage according to surface area appears not to reduce either pharmacokinetic or pharmacodynamic variability. PMID:9744507

  9. 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.

  10. 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

  11. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial.

    PubMed

    Earl, Helena M; Hiller, Louise; Howard, Helen C; Dunn, Janet A; Young, Jennie; Bowden, Sarah J; McDermaid, Michelle; Waterhouse, Anna K; Wilson, Gregory; Agrawal, Rajiv; O'Reilly, Susan; Bowman, Angela; Ritchie, Diana M; Goodman, Andrew; Hickish, Tamas; McAdam, Karen; Cameron, David; Dodwell, David; Rea, Daniel W; Caldas, Carlos; Provenzano, Elena; Abraham, Jean E; Canney, Peter; Crown, John P; Kennedy, M John; Coleman, Robert; Leonard, Robert C; Carmichael, James A; Wardley, Andrew M; Poole, Christopher J

    2017-06-01

    The tAnGo trial was designed to investigate the potential role of gemcitabine when added to anthracycline and taxane-containing adjuvant chemotherapy for early breast cancer. When this study was developed, gemcitabine had shown significant activity in metastatic breast cancer, and there was evidence of a favourable interaction with paclitaxel. tAnGo was an international, open-label, randomised, phase 3 superiority trial that enrolled women aged 18 years or older with newly diagnosed, early-stage breast cancer who had a definite indication for chemotherapy, any nodal status, any hormone receptor status, Eastern Cooperative Oncology Group performance status of 0-1, and adequate bone marrow, hepatic, and renal function. Women were recruited from 127 clinical centres and hospitals in the UK and Ireland, and randomly assigned (1:1) to one of two treatment regimens: epirubicin, cyclophosphamide, and paclitaxel (four cycles of 90 mg/m(2) intravenously administered epirubicin and 600 mg/m(2) intravenously administered cyclophosphamide on day 1 every 3 weeks, followed by four cycles of 175 mg/m(2) paclitaxel as a 3 h infusion on day 1 every 3 weeks) or epirubicin, cyclophosphamide, and paclitaxel plus gemcitabine (the same chemotherapy regimen as the other group, with the addition of 1250 mg/m(2) gemcitabine to the paclitaxel cycles, administered intravenously as a 0·5 h infusion on days 1 and 8 every 3 weeks). Patients were randomly assigned by a central computerised deterministic minimisation procedure, with stratification by country, age, radiotherapy intent, nodal status, and oestrogen receptor and HER-2 status. The primary endpoint was disease-free survival and the trial aimed to detect 5% differences in 5-year disease-free survival between the treatment groups. Recruitment completed in 2004 and this is the final, intention-to-treat analysis. This trial is registered with EudraCT (2004-002927-41), ISRCTN (51146252), and ClinicalTrials.gov (NCT00039546). Between Aug 22

  12. 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

  13. PUMA gene transfection can enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells.

    PubMed

    Sun, C-G; Zhuang, J; Teng, W-J; Wang, Z; Du, S-S

    2015-05-29

    We explored whether p53 upregulated modulator of apoptosis (PUMA) gene transfection could enhance the sensitivity of epirubicin-induced apoptosis of MCF-7 breast cancer cells. The liposome-mediated recombinant eukaryotic expression vector PU-MA-pCDNA3 and empty vector plasmid were stably transfected into MCF-7 cells. Epirubicin (0.01-100 μM) was applied to MCF-7, MCF-7/PUMA, and MCF-7/pCDNA3 cells for 72 h. The MTT assay was used to calculate the cell survival rate in each group, and the 50% inhibitory concentration (IC50) was calculated. The IC50 values of epirubicin in MCF-7, MCF-7/PUMA, and MCF-7/pCDNA3 cells were 13 ± 1.4, 1.8 ± 0.2, and 10.7 ± 1.3 μM, respectively. The sensitivity of MCF-7/PUMA cells to epirubicin increased 7.2-fold. Epirubicin induced apoptosis in MCF-7 cells dose-dependently, but MCF-7/PUMA cell-induced apoptosis was more significant compared to controls. Low concentrations of epirubicin (0.1 μM) caused low levels of apoptosis of MCF-7/pCDNA3 (1.15 ± 0.26%) and MCF-7 cells (0.9 ± 0.24%), but significantly induced apoptosis of MCF-7/PUMA cells (6.44 ± 1.46%). High epirubicin concentration (1 μM) induced apoptosis in each group, but the epirubicin MCF-7/PUMA apoptosis rate (35.47 ± 9.36%) was significantly higher than that of MCF-7 (12.6 ± 3.73%) and MCF-7/ pCDNA3 (15.2 ± 5.17%) cells (P < 0 01). Flow cytometry and TUNEL assays for apoptosis detection showed similar results. PUMA protein expression in MCF-7/PUMA cells was significantly higher than that in MCF-7 and MCF-7/pCDNA3 cells by Western blot analysis. There-fore, stable transfection of PUMA can significantly enhance epirubicin-induced apoptosis sensitivity of MCF-7 breast cancer cells.

  14. Comparison of epirubicin and doxorubicin cardiotoxicity in children and adolescents treated within the German Cooperative Soft Tissue Sarcoma Study (CWS).

    PubMed

    Stöhr, W; Paulides, M; Brecht, I; Kremers, A; Treuner, J; Langer, T; Beck, J D

    2006-01-01

    Up to now, cardiotoxicity of epirubicin has been studied almost exclusively in adult cancer patients. The aim of this study was to investigate epirubicin in children and adolescents, in comparison with doxorubicin. About 172 soft tissue sarcoma patients (mean age at diagnosis: 8.3 years), treated with epirubicin (median cumulative dose: 450 mg/m2) or doxorubicin (median cumulative dose: 240 mg/m2) within the high-risk group of the CWS-96 study, were examined in a prospective multicentre study. Heart function was analysed by echocardiography, measuring left-ventricular fractional shortening (FS). The median follow up was 27.7 months. Incidence of clinically manifest cardiomyopathy was 0% (0/60; 95% CI: 0-6.0%) in patients treated with epirubicin, and 0.9% (1/108; 95% CI: 0-5.1%) in patients treated with doxorubicin. A further three patients showed subclinical cardiomyopathy. There was no difference in FS between the two treatment arms. Cardiotoxicity was low in our study. For the short term, cardiotoxicity seems to be only a minor problem in patients treated with epirubicin as applied in this cohort.

  15. 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.

  16. Influence of Alternative Tubulin Inhibitors on the Potency of a Epirubicin-Immunochemotherapeutic Synthesized with an Ultra Violet Light-Activated Intermediate

    PubMed Central

    Coyne, C. P.; Jones, Toni; Bear, Ryan

    2015-01-01

    Immunochemotherapeutics, epirubicin-(C3-amide)-SS-[anti-HER2/neu] with an internal disulfide bond, and epirubicin-(C3-amide)-[anti-HER2/neu] were synthesized utilizing succinimidyl 2-[(4,4′-azipentanamido) ethyl]-1,3′-dithioproprionate or succinimidyl 4,4-azipentanoate respectively. Western blot analysis was used to determine the presence of any immunoglobulin fragmentation or IgG-IgG polymerization. Retained HER2/neu binding characteristics of epirubicin-(C3-amide)-[anti-HER2/neu] and epirubicin-(C3-amide)-SS-[anti-HER2/neu] were validated by cell-ELISA using a mammary adenocarcinoma (SKBr-3) population that highly over-expresses trophic HER2/neu receptor complexes. Cytotoxic anti-neoplastic potency of epirubicin-(C3-amide)-[anti-HER2/neu] and epirubicin-(C3-amide)-SS-[anti-HER2/neu] between epirubicin-equivalent concentrations of 10−10 M and 10−6 M was determined by measuring the vitality/proliferation of chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3 cell type). Cytotoxic anti-neoplastic potency of benzimidazoles (albendazole, flubendazole, membendazole) and griseofulvin were assessed between 0-to-2 μg/ml and 0-to-100 μg/ml respectively while mebendazole and griseofulvin were analyzed at fixed concentrations of 0.35 μg/ml and 35 g/ml respectively in dual combination with gradient concentrations of epirubicin-(C3-amide)-[anti-HER2/neu] and epirubicin-(C3-amide)-SS-[anti-HER2/neu]. Cytotoxic anti-neoplastic potency for epirubicin-(C3-amide)-[anti-HER2/neu] and epirubicin-(C3-amide)-SS-[anti-HER2/neu] against chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3) was nearly identical at epirubicin-equivalent concentrations of 10−10 M and 10−6 M. The benzimadazoles also possessed cytotoxic anti-neoplastic activity with flubendazole and albendazole being the most and least potent respectively. Similarly, griseofulvin had cytotoxic anti-neoplastic activity and was more potent than methylselenocysteine. Both mebendazole and griseofulvin

  17. 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

  18. 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.

  19. 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

  20. 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

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

    PubMed

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

    2017-05-15

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

  2. 5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial.

    PubMed

    Del Mastro, Lucia; Levaggi, Alessia; Michelotti, Andrea; Cavazzini, Giovanna; Adami, Francesca; Scotto, Tiziana; Piras, Margherita; Danese, Saverio; Garrone, Ornella; Durando, Antonio; Accortanzo, Valeria; Bighin, Claudia; Miglietta, Loredana; Pastorino, Simona; Pronzato, Paolo; Castiglione, Federico; Landucci, Elisabetta; Conte, PierFranco; Bruzzi, Paolo

    2016-01-01

    The study was designed to compare an anthracycline-containing regimen to a regimen combining both anthracycline and paclitaxel as adjuvant therapy for high-risk breast cancer patients. In this multicenter, randomized phase-III trial, node-positive early breast cancer patients were randomly assigned to receive either 6 cycles of FEC (5-fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2), day 1, every 3 weeks) or 4 cycles of EP (epirubicin 90 mg/m(2) and paclitaxel 175 mg/m(2), day 1, every 3 weeks). The primary endpoint was overall survival (OS). Secondary endpoints included toxicity and event-free survival (EFS). From 1996 to 2001, 1055 patients were enrolled. At a median follow-up of 12.8 years, 335 deaths had been recorded. The 10-year OS was 73 % (95 % CI 69-77) in the FEC arm and 74 % (95 % CI 70-78) in the EP arm (p = 0.405). The 10-year EFS was 51 % (95 % CI 45-56) in the FEC arm and 49 % (95 % CI 44-55) in the EP arm (p = 0.572). No difference in the hazard of death was observed (HR for EP 0.85, 95 % CI 0.68-1.06, p = 0.15). Patients treated with FEC experienced more frequently nausea and vomiting, stomatitis, and leukopenia as compared to patients treated with EP. Toxicities which occurred more frequently with EP were anemia, fever, myalgias, and neurotoxicity. Our study failed to demonstrate a superiority of an adjuvant treatment with four EP as compared to six FEC in node-positive breast cancer patients.

  3. Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

    PubMed

    Zhang, Hua; Shen, Wei-sheng; Gao, Chun-heng; Deng, Li-chun; Shen, Dong

    2012-06-01

    Salidroside [2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated. The aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin. Sixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n = 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2. A decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p < 0.05) and 400 mg/m2 (1.68 ± 0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside. Salidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

  4. Co-encapsulation of chrysophsin-1 and epirubicin in PEGylated liposomes circumvents multidrug resistance in HeLa cells.

    PubMed

    Lo, Yu-Li; Tu, Wei-Chen

    2015-12-05

    Chrysophsin-1, an amphipathic alpha-helical antimicrobial peptide, is isolated from the gills of the red sea bream and possesses different structure and mechanism(s) in comparison with traditional multidrug resistance (MDR) modulators. For the purpose of reducing off-target normal cell toxicity, it is rational to incorporate chrysophsin-1 and epirubicin in a PEGylated liposomal formulation. In the present study, we report a multifunctional liposomes with epirubicin as an antineoplastic agent and an apoptosis inducer, as well as chrysophsin-1 as a MDR transporter inhibitor and an apoptosis modulator in human cervical cancer HeLa cells. Co-incubation of HeLa cells with PEGylated liposomal formulation of epirubicin and chrysophsin-1 resulted in a significant increase in the cytotoxicity of epirubicin. The liposomal formulations of epirubicin and/or chrysophsin-1 were shown to considerably improve the intracellular H2O2 and O2(-) levels of HeLa cells. Furthermore, these treatments were found to extensively reduce mRNA expression levels of MDR1, MRP1, and MRP2. The addition of chrysophsin-1 in liposomes was demonstrated to substantially enhance the intracellular accumulation of epirubicin in HeLa cells. Moreover, the PEGylated liposomes of epirubicin and chrysophsin-1 were also found to significantly increase the mRNA expressions of p53, Bax, and Bcl-2. The ratio of Bax to Bcl-2 was noticeably amplified in the presence of these formulations. Apoptosis induction was also validated by chromatin condensation, a reduction in mitochondrial membrane potential, the increased sub-G1 phase of cell cycle, and more populations of apoptosis using annexin V/PI assay. These formulations were verified to increase the activity and mRNA expression levels of caspase-9 and caspases-3. Collectively, our findings provide the first evidence that cotreatment with free or liposomal chrysophsin-1 and epirubicin leads to cell death in human cervical cancer cells through the ROS

  5. Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract.

    PubMed

    Sasu, Alciona; Herman, Hildegard; Mariasiu, Teodora; Rosu, Marcel; Balta, Cornel; Anghel, Nicoleta; Miutescu, Eftimie; Cotoraci, Coralia; Hermenean, Anca

    2015-10-01

    Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with control. p53 expression was found in all analyzed tissues and decreased by high dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the Epi groups for all analyzed tissues was almost suppressed at 100 mg/kg Sy co-treatment. Histological aspect and goblet cell count were restored at a highest dose of Sy for both small and large intestine. In conclusion, our findings suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity and was effective in reducing the severity indicators of gastrointestinal mucositis in mice.

  6. Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer.

    PubMed

    Appel, Jon M; Zerahn, Bo; Møller, Susanne; Christensen, Heidi M; Søgaard, Peter; Ejlertsen, Bent; Fogh-Andersen, Niels; Jensen, Benny V; Nielsen, Dorte L

    2012-11-01

    Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment. The study-population was a historical cohort comprising 980 women who were randomized to receive one of two adjuvant regimens for treatment for BC: 7-9 cycles of cyclophosphamide-epirubicin-5-fluorouracil [CEF (600 + 60 + 600 mg/m(2))] or cyclophosphamide-methotrexate-5- fluorouracil [CMF (600 + 40 + 600 mg/m(2))]. We collected information in national registries of death and diagnoses and a sample of 77 survivors was examined with tissue-Doppler imaging (TDI), echocardiography, radionuclide ventriculography and N-terminal-pro-B-type-natriuretic peptide (NT-proBNP), an established marker for heart failure. Median follow-up was 12 years (39 days-20 years). Fifty-one percent had died. Incidence of CHF was 2.6/1000/year and equal in the treatment groups. In the sample, individuals who had received CEF showed no cardiac impairment when compared to individuals who received CMF. NT-proBNP-levels were within normal limits but higher in the CEF-group than in the CMF-group (confidence limits 105-226%, p = 0.03). Results of our study seem reassuring regarding the long-term risk of cardiotoxicity following low-dose adjuvant epirubicin treatment. However, larger, longitudinal studies are needed to establish the clinical implications.

  7. Synthesis of a Covalent Epirubicin-(C3-amide)-Anti-HER2/neu Immunochemotherapeutic Utilizing a UV-Photoactivated Anthracycline Intermediate

    PubMed Central

    Jones, Toni; Bear, Ryan

    2012-01-01

    Abstract The C3-monoamine on the carbohydrate moiety (daunosamine -NH2-3′) of epirubicin was reacted under anhydrous conditions with succinimidyl 4,4-azipentanoate to create a covalent UV-photoactivated epirubicin-(C3-amide) intermediate with primary amine-reactive properties. A synthetic covalent bond between the UV-photoactivated epirubicin-(C3-amide) intermediate and the ɛ-amine of lysine residues within the amino acid sequence of anti-HER2/neu monoclonal immunoglobulin was subsequently created by exposure to UV light (354 nm) for 15 minutes. Size-separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis combined with immunodetection analysis and chemiluminescent autoradiographic imaging revealed a lack of IgG-IgG polymerization or degradative protein fragmentation of the covalent epirubicin-(C3-amide)-[anti-HER2/neu] immunochemotherapeutic. Retained binding-avidity of epirubicin-(C3-amide)-[anti-HER2/neu] was validated by cell-ELISA utilizing monolayer populations of chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 which highly overexpress membrane-associated HER2/neu complexes. Between epirubicin-equivalent concentrations of 10−10 to 10−6 M the covalent epirubicin-(C3-amide)-[anti-HER2/neu] immunochemotherapeutic consistently evoked levels of cytotoxic anti-neoplastic potency that were highly analogous to chemotherapeutic-equivalent concentrations of epirubicin. Cytotoxic anti-neoplastic potency of epirubicin-(C3-amide)-[anti-HER2/neu] against chemotherapeutic-resistant mammary adenocarcinoma SKBr-3 challenged with epirubicin-(C3-amide)-[anti-HER2/neu] at an epirubicin-equivalent concentration of 10−6 M was 88.5% (e.g., 11.5% residual survival). Between final epirubicin-equivalent concentrations of 10−8 and 10−7 M there was a marked threshold increase in the mean cytotoxic anti-neoplastic activity for epirubicin-(C3-amide)-[anti-HER2/neu] from 9.9% to 66.9% (90.2% to 33.1% residual survival). PMID:22191802

  8. Effectiveness of scalp cooling in reducing alopecia caused by epirubicin treatment of advanced breast cancer.

    PubMed

    Robinson, M H; Jones, A C; Durrant, K D

    1987-10-01

    The value of scalp cooling in the prevention of alopecia was investigated in 32 patients with advanced breast cancer who were given a mean of four courses of 40-80 mg/m2 of epirubicin. None of the 15 patients free from liver metastases who received scalp cooling required a wig, whereas four of eight similar patients who did not receive scalp cooling did require a wig. Abnormalities of aspartate transaminase and alkaline phosphatase pretreatment were predictive for reduced efficacy of scalp cooling, but not a contraindication to its use.

  9. Epirubicin loading in poly(butyl cyanoacrylate) nanoparticles manifests via altered intracellular localization and cellular response in cervical carcinoma (HeLa) cells.

    PubMed

    Evangelatov, Aleksandar; Skrobanska, Ralica; Mladenov, Nikola; Petkova, Milena; Yordanov, Georgi; Pankov, Roumen

    2016-09-01

    Drug loading into nanocarriers is used to facilitate drug delivery to target cells and organs. We have previously reported a change in cellular localization of epirubicin after loading to poly(butyl cyanoacrylate) (PBCA) nanoparticles. We aimed to further investigate the altered cellular localization and cellular responses to the described drug formulation. HeLa cells were treated with epirubicin-loaded PBCA nanoparticles prepared by the pre-polymerization method. A systematic study was performed to evaluate the formulation cytotoxicity. Cellular localization and uptake of the formulation as well as cellular response to the treatment were evaluated. Our studies revealed decreased cytotoxicity of the nanoparticle-formulated epirubicin compared to the free drug as well as a noticeable change in the drug's intracellular localization. Epirubicin-loaded nanoparticles were internalized via endocytosis, accumulated inside endosomal vesicles and induced a two-fold stronger pro-apoptotic signal when compared to the free drug. The level of the tumor suppressor protein p53 in HeLa cells increased significantly upon treatment with free epirubicin, but remained relatively unchanged when cells were treated with equivalent dose of nanoparticle-loaded drug, suggesting a possible shift from p53-dependent DNA/RNA intercalation-based induction of cytotoxicity by free epirubicin to a caspase 3-induced cell death by the epirubicin-loaded PBCA formulation.

  10. 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.

  11. 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

  12. Pharmacokinetics of doxorubicin and epirubicin in mice during chlorpromazine-induced hypothermia.

    PubMed

    Lundgren-Eriksson, L; Carlsson, A; Eksborg, S; Ryd, W; Vesanen, R; Hultborn, R

    1997-01-01

    Blood concentrations of doxo- and epirubicin were studied in mice after i.v. or i.p. administration under normal and hypothermic conditions. The animals either were pretreated i.p. with chlorpromazine at 15 mg/kg and allowed to cool to a rectal temperature of 28 degrees C or were given saline i.p. with their rectal temperature remaining at 37 degrees C. The anthracyclines were 14-14C-labeled and were given at a dose of 0.85 mg/kg. Blood samples were taken at 5, 15, and 25 min and 2, 6, 24, and 48 hours after injection and were analyzed by liquid scintillation counting. The blood concentration related to time was similar for the two anthracyclines. The peak concentration was highest for i.v. administration and was higher for the hypothermic groups. The peak concentration and the area under the curve were highest under hypothermic conditions. The terminal half-life was longer after i.p. administration. The ratio calculated for the blood concentration under hypothermic/normothermic conditions over time was substantially increased after i.p. administration, the increase being most pronounced for epirubicin. The pharmacokinetic characteristics found might be related to the anthracycline toxicity encountered in tumor-inoculated mice treated at different body temperatures.

  13. 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

  14. HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

    PubMed Central

    Tiezzi, Daniel G; Andrade, Jurandyr M; Ribeiro-Silva, Alfredo; Zola, Fábio E; Marana, Heitor RC; Tiezzi, Marcelo G

    2007-01-01

    Background Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. Methods Sixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. Results Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. Conclusion Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination. PMID:17324279

  15. 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.

  16. Transcatheter Arterial Embolization for Tumor Seeding in the Chest Wall After Radiofrequency Ablation for Hepatocellular Carcinoma

    SciTech Connect

    Shibata, Toshiya Shibata, Toyomichi; Maetani, Yoji; Kubo, Takeshi; Nishida, Naoshi; Itoh, Kyo

    2006-06-15

    Tumor seeding in the chest wall was depicted at follow-up CT obtained 9 months after radiofrequency ablation for hepatocellular carcinoma. Transcatheter arterial embolization was successfully performed, injecting emulsion of 10 mg of epirubicin and 1 ml of iodized oil followed by gelatin sponge particles via the microcatheter placed in the right eleventh intercostal artery. The patient died of tumor growth in the liver one year after the embolization, but no progression of the tumor seeding was noted during the follow-up period. We conclude that transcatheter arterial embolization was effective for the control of tumor seeding after radiofrequency ablation for hepatocellular carcinoma.

  17. Stability of solutions of doxorubicin and epirubicin in plastic minibags for intravesical use after storage at -20 degrees C and thawing by microwave radiation.

    PubMed

    Keusters, L; Stolk, L M; Umans, R; Van Asten, P

    1986-06-20

    Doxorubicin and epirubicin solutions in plastic minibags for intravesical use were stored at -20 degrees C and thawed at room temperature or by microwave radiation. Concentrations were measured with HPLC and TLC. Doxorubicin and epirubicin solutions could be frozen and stored at -20 degrees C during at least two and four weeks, respectively, and subsequently thawed without loss of content. When the thawed doxorubicin solutions were refrozen and thawed again five weeks later, only a slight decrease of content was measured.

  18. 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.

  19. 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.

  20. Saline infusion sonohysterography.

    PubMed

    2004-01-01

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

  1. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    1974-01-01

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

  2. 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.

  3. The Early Predictive Value of Right Ventricular Strain in Epirubicin-Induced Cardiotoxicity in Patients with Breast Cancer

    PubMed Central

    Chang, Wei-Ting; Shih, Jhih-Yuan; Feng, Yin-Hsun; Chiang, Chun-Yen; Kuo, Yu Hsuan; Chen, Wei-Yu; Wu, Hong-Chang; Cheng, Juei-Tang; Wang, Jhi-Joung; Chen, Zhih-Cherng

    2016-01-01

    Background As cancer therapies have improved, patient life spans have been extended but quality of life has been threatened by chemotherapy induced cardiotoxicity. Most cardiac complications remain unobserved until specific symptoms develop. Speckle-tracking echocardiography is a sensitive imaging modality in detecting early occult myocardial dysfunction. Methods A total number of 35 patients newly diagnosed with breast cancer and preparing for epirubicin therapy were prospectively recruited. Echocardiography, including speckle-tracking echocardiography, was performed sequentially at baseline (T1), after the first cycle (T2) and after the third cycle (T3) of epirubicin. At each visit, the severity of dyspnea was evaluated by the assessment scale. Results Compared with the baseline, right ventricular longitudinal strain (RVLS_FW) at T2 significantly declined (-22.49 ± 4.97 vs. -18.48 ± 4.46, p = 0.001), which was also positively associated with the development of dyspnea (R2 = 0.8, p = 0.01). At T3, both the left ventricular global longitudinal strain and RVLS_FW were significantly impaired (-21.4 ± 4.12 vs. -16.94 ± 6.81%; -22.49 ± 4.97 vs. -16.86 ± 7.27%, p = 0.01; 0.001, respectively). Also, the accumulating dose of epirubicin positively correlated with the development of dyspnea (R2 = 0.38, p = 0.04) and the decline of RVLS_FW (R2 = 0.53, p = 0.02). Notably, compared with the other echocardiographic parameters only RVLS_FW at the early stage (T2) significantly correlated with the development of dyspnea (odds ratio: 1.84, 95% confidence interval: 1.22-2.78, p = 0.04). Conclusions RVLS_FW sensitively predicts dyspnea development in breast cancer patients receiving epirubicin therapy. However, larger scale studies are required to validate its role in long-term patient survival. PMID:27713603

  4. An Attempt to Shorten Loading Time of Epirubicin into DC Beads(®) Using Vibration and a Sieve.

    PubMed

    Sonoda, Akinaga; Nitta, Norihisa; Yamamoto, Takefumi; Tomozawa, Yuki; Ohta, Shinichi; Watanabe, Shobu; Murata, Kiyoshi

    2017-04-01

    We investigated the possibility of shortening the time required for loading epirubicin into calibrated polyvinyl alcohol-based hydrogel beads (DC Beads(®)) to be used for transarterial chemoembolization. After separating the beads suspended in phosphate-buffered saline (PBS) solution by the use of a sieve (clearance 75 µm), epirubicin hydrochloride (EH) was loaded for 20, 30, or 60 s under vibration into DC beads. The EH loading rate into conventionally prepared (control) beads, i.e., beads loaded for 30 min without vibration, and vibration-loaded beads were calculated from the residual EH concentration in the bead-depleted EH solution. The amount of EH eluted from conventionally and vibration-loaded samples into a PBS solution (pH 7.0) was measured at 15 and 30 min and 1, 2, 6, 12, and 24 h. We also recorded the inhibitory effect of the PBS solution on the loading time. Using frozen sections, the EH load in the beads was evaluated visually under a fluorescence microscope. Spectrophotometry (495 nm) showed that the loading rate was 98.98 ± 0.34, 99.02 ± 0.32, and 99.50 ± 0.11 % with 20-, 30-, and 60-s vibration, respectively. The eluted rate was statistically similar between vibration- and statically loaded (control) beads. The PBS solution hampered EH loading into the beads. Visually, the distribution of EH in conventionally and vibration-loaded DC beads was similar. The use of vibration and the removal of PBS solution when epirubicin hydrochloride was loaded into DC beads dramatically shortened the loading time of epirubicin hydrochloride into DC beads.

  5. A phase I trial of panobinostat and epirubicin in solid tumors with a dose expansion in patients with sarcoma

    PubMed Central

    Thomas, S.; Aggarwal, R.; Jahan, T.; Ryan, C.; Troung, T.; Cripps, A. M.; Raha, P.; Thurn, K. T.; Chen, S.; Grabowsky, J. A.; Park, J.; Hwang, J.; Daud, A.; Munster, P. N.

    2016-01-01

    Background Treatment options for sarcoma are limited. Histone deacetylase inhibitors increase the efficacy of topoisomerase II inhibitors by promoting access to chromatin and by down-regulating DNA repair. Thus, combined panobinostat and epirubicin therapy was evaluated to treat refractory sarcoma. Patients and methods Patients with advanced solid tumors were enrolled in a 3 + 3 dose-escalation phase I trial of panobinostat given on days 1, 3, and 5 followed by 75 mg/m2 of epirubicin on day 5 in 21-day cycles, with a dose expansion at maximum tolerated dose (MTD) in 20 sarcoma patients. Peripheral blood mononucleocyte histone acetylation was also evaluated. Results Forty patients received 20–60 mg panobinostat. Dose-limiting toxicities included thrombocytopenia, febrile neutropenia, and fatigue at 60 mg, defining a panobinostat MTD at 50 mg. Four responses were seen in 37 assessable patients, all after progression on prior topoisomerase II inhibitors. For those with sarcoma, 12 of 20 derived clinical benefit (1 partial response and 11 stable disease, median overall survival 8.3 months), including 8 of 14 previously progressed on topoisomerase II therapy. Treatment benefits correlated with increased histone acetylation and decreased neutrophil count on day 5. Conclusions Panobinostat and epirubicin treatment is well tolerated and may reverse anthracycline resistance. Changes in histone acetylation and associated decrease in neutrophil count correlated with clinical benefit and warrant investigation as predictive biomarkers. Clinical trial This trial is registered at www.Clinicaltrials.gov, Identifier: NCT00878904. PMID:26903311

  6. A nanostructure of functional targeting epirubicin liposomes dually modified with aminophenyl glucose and cyclic pentapeptide used for brain glioblastoma treatment.

    PubMed

    Zhang, Cheng-Xiang; Zhao, Wei-Yu; Liu, Lei; Ju, Rui-Jun; Mu, Li-Min; Zhao, Yao; Zeng, Fan; Xie, Hong-Jun; Yan, Yan; Lu, Wan-Liang

    2015-10-20

    The objectives of the present study were to develop functional targeting epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB), treating glioblastoma, and disabling neovascularization. The studies were performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The results showed that the constructed liposomes had a high encapsulation efficiency for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood component-containing system; were significantly able to be transported across the BBB; and exhibited efficacies in killing glioblastoma cells and in destroying glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action mechanisms of functional targeting epirubicin liposomes correlated with the following features: the long circulation in the blood system, the ability to be transported across the BBB via glucose transporter-1, and the targeting effects on glioblastoma cells and on the endothelial cells of the glioblastoma neovasculature via the integrin β3 receptor. In conclusion, functional targeting epirubicin liposomes could be used as a potential therapy for treating brain glioblastoma and disabling neovascularization in brain glioblastomas.

  7. A nanostructure of functional targeting epirubicin liposomes dually modified with aminophenyl glucose and cyclic pentapeptide used for brain glioblastoma treatment

    PubMed Central

    Zhang, Cheng-Xiang; Zhao, Wei-Yu; Liu, Lei; Ju, Rui-Jun; Mu, Li-Min; Zhao, Yao; Zeng, Fan; Xie, Hong-Jun; Yan, Yan; Lu, Wan-Liang

    2015-01-01

    The objectives of the present study were to develop functional targeting epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB), treating glioblastoma, and disabling neovascularization. The studies were performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The results showed that the constructed liposomes had a high encapsulation efficiency for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood component-containing system; were significantly able to be transported across the BBB; and exhibited efficacies in killing glioblastoma cells and in destroying glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action mechanisms of functional targeting epirubicin liposomes correlated with the following features: the long circulation in the blood system, the ability to be transported across the BBB via glucose transporter-1, and the targeting effects on glioblastoma cells and on the endothelial cells of the glioblastoma neovasculature via the integrin β3 receptor. In conclusion, functional targeting epirubicin liposomes could be used as a potential therapy for treating brain glioblastoma and disabling neovascularization in brain glioblastomas. PMID:26418720

  8. 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.

  9. RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment

    PubMed Central

    Kongsema, M; Zona, S; Karunarathna, U; Cabrera, E; Man, E P S; Yao, S; Shibakawa, A; Khoo, U-S; Medema, R H; Freire, R; Lam, E W-F

    2016-01-01

    The forkhead box M1 (FOXM1) transcription factor has a central role in genotoxic agent response in breast cancer. FOXM1 is regulated at the post-translational level upon DNA damage, but the key mechanism involved remained enigmatic. RNF168 is a ubiquitination E3-ligase involved in DNA damage response. Western blot and gene promoter-reporter analyses showed that the expression level and transcriptional activity of FOXM1 reduced upon RNF168 overexpression and increased with RNF168 depletion by siRNA, suggesting that RNF168 negatively regulates FOXM1 expression. Co-immunoprecipitation studies in MCF-7 cells revealed that RNF168 interacted with FOXM1 and that upon epirubicin treatment FOXM1 downregulation was associated with an increase in RNF168 binding and conjugation to the protein degradation-associated K48-linked polyubiquitin chains. Consistently, RNF168 overexpression resulted in an increase in turnover of FOXM1 in MCF-7 cells treated with the protein synthesis inhibitor cycloheximide. Conversely, RNF168, knockdown significantly enhanced the half-life of FOXM1 in both absence and presence of epirubicin. Using a SUMOylation-defective FOXM1-5x(K>R) mutant, we demonstrated that SUMOylation is required for the recruitment of RNF168 to mediate FOXM1 degradation. In addition, clonogenic assays also showed that RNF168 mediates epirubicin action through targeting FOXM1, as RNF168 could synergise with epirubicin to repress clonal formation in wild-type but not in FOXM1-deficient mouse embryo fibroblasts (MEFs). The physiological relevance of RNF168-mediated FOXM1 repression is further emphasized by the significant inverse correlation between FOXM1 and RNF168 expression in breast cancer patient samples. Moreover, we also obtained evidence that RNF8 recruits RNF168 to FOXM1 upon epirubicin treatment and cooperates with RNF168 to catalyse FOXM1 ubiquitination and degradation. Collectively, these data suggest that RNF168 cooperates with RNF8 to mediate the ubiquitination and

  10. 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.

  11. Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

    PubMed Central

    Sayal, Karen; Gounaris, Ioannis; Basu, Bristi; Freeman, Sue; Moyle, Penny; Hosking, Karen; Iddawela, Mahesh; Jimenez-Linan, Mercedes; Abraham, Jean; Brenton, James; Hatcher, Helen; Earl, Helena; Parkinson, Christine

    2015-01-01

    Objective Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. Methods Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. Results Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. Conclusions Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after

  12. [Results of clinical study with epirubicin hydrochloride injectable solution for superficial bladder cancer. IMI28 Injectable Solution Study Group for Superficial Bladder Cancer].

    PubMed

    Kotake, T; Koyanagi, T; Akaza, H; Shimazaki, J; Ito, H; Hosaka, M; Okajima, E; Saito, Y; Miyanaga, N; Kuroda, M; Hirao, Y

    1998-07-01

    A 7-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with superficial bladder carcinoma. Epirubicin-RTU at the dose of 60 mg/30 ml was administered by intravesical instillation once daily for three (3) consecutive days and a 4-day drug-free interval followed; then the above intravesical instillation of Epirubicin-RTU was repeated for three consecutive days. All 20 registered cases were eligible, and 18 cases completed the whole course of the study. In 18 completers, CR was observed in 12 cases and PR was observed in one (1) case, for an efficacy rate of 72.2%. The primary adverse reaction was bladder irritation including pollakiuria 85.0% (17/20), miction pain 85.0% (17/20), and hematuria 80.0% (16/20), which were all reversible and tolerable. In urinalysis, urinary sediment showed leukocytes and erythrocytes, and proteinuria was observed. All were reversible. From the above results, this new formulation of Epirubicin-RTU was considered useful for the treatment of superficial bladder carcinoma.

  13. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration

    PubMed Central

    Lo, Yu-Li; Lin, Yijun; Lin, Hong-Ru

    2014-01-01

    Temperature sensitive Pluronic (Plu) and pH-sensitive polyacrylic acid (PAA) were successfully mixed in different ratios to form in situ gelling formulations for colon cancer therapy. The major formulations were prepared as the liquid and solid suppository dosage forms. Epirubicin (Epi) was chosen as a model anticancer drug. In vitro characterization and in vivo pharmacokinetics and therapeutic efficacy of Epi in six Plu/PAA formulations were evaluated. Our in vitro data indicate that Epi in Plu 14%/PAA 0.75% of both solid and liquid suppositories possess significant cytotoxicity, strong bioadhesive force, long-term appropriate suppository base, sustained release, and high accumulation of Epi in rat rectums. These solid and liquid suppositories were retained in the upper rectum of Sprague-Dawley (SD) rats for at least 12 h. An in vivo pharmacokinetic study using SD rats showed that after rectal administration of solid and liquid suppositories, Epi had greater area under the curve and higher relative bioavailability than in a rectal solution. These solid and liquid suppositories exhibited remarkable inhibition on the tumor growth of CT26 bearing Balb/c mice in vivo. Our findings suggest that in situ thermogelling and mucoadhesive suppositories demonstrate a great potential as colon anticancer delivery systems for protracted release of chemotherapeutic agents. PMID:24384838

  14. The effectiveness of scalp cooling in preventing alopecia for patients receiving epirubicin and docetaxel.

    PubMed

    Macduff, C; Mackenzie, T; Hutcheon, A; Melville, L; Archibald, H

    2003-06-01

    The aim of this study was to establish the effectiveness of scalp cooling in preventing alopecia for patients with breast cancer who received the trial combination chemotherapy of Epirubicin and Docetaxel. Doubt remains about the general effectiveness of scalp cooling in preventing hair loss for patients receiving chemotherapy. There is very little information available about its specific effectiveness with combinations of Taxanes and Anthracycline drugs. Of the 40 patients who received this drug combination, 10 were included in a pilot study whereas the remaining 30 constituted the main study sample. A randomized controlled study was undertaken whereby the intervention group received scalp cooling via gel cool caps and the control group received no specific preventative intervention. Nurses assessed participants' hair loss using a modified version of the WHO scale at seven time points and also recorded hair loss photographically. Two independent experts rated the photographs using the same scale. Patients self-reported in relation to overall hair loss, hair condition, levels of emotional upset, negativity about appearance, hair re-growth and wig use. Significantly greater hair loss was apparent in the control group during most of the treatment period. However, the level of protection afforded by the cool caps was relatively poor with this chemotherapy combination. The marginal benefits of scalp cooling in this context must be clearly explained to patients.

  15. Epirubicin pretreatment enhances NK cell-mediated cytotoxicity against breast cancer cells in vitro.

    PubMed

    Feng, Hui; Dong, Ying; Wu, Jing; Qiao, Yuan; Zhu, Ge; Jin, Haofan; Cui, Jiuwei; Li, Wei; Liu, Yong-Jun; Chen, Jingtao; Song, Yanqiu

    2016-01-01

    Anthracycline-based chemotherapy is a conventional treatment for breast cancer. However, it can negatively affect host immune function and thereby impair patients' quality of life. Boosting the host immune system and reducing the adverse effect of chemotherapy are important for effective cancer treatment. Natural killer (NK) cells stimulate immune responses against cancer; autologous immune enhancement therapy with NK cells prolongs patient survival without significant adverse effects. This study investigated the effects of combined treatment with the anthracycline agent epirubicin (EPI) and NK cells on human breast cancer cells. NK cells were obtained by autologous adoptive cell transfer from breast cancer patients and amplified for 14 days in vitro. The cytotoxicity of NK cells against breast cancer cells was higher following EPI (5.0 μg/ml) pretreatment than without EPI pretreatment or application of EPI alone. The expression of NKG2D ligands [unique long 16-binding protein (ULBP) 1, ULBP2, and major histocompatibility complex class I-related chain A] in breast cancer cells was upregulated by pretreatment with EPI, which also increased the secretion of interferon-γ and tumor necrosis factor-α and expression of perforin and granzyme B in NK cells. These results indicate that EPI-NK cell treatment has synergistic cytotoxic effects against breast cancer cells, and suggest that anthracycline-based chemotherapy and NK cell-based immunotherapy can be combined for more effective breast cancer treatment.

  16. RGD-peptide conjugated inulin-ibuprofen nanoparticles for targeted delivery of Epirubicin.

    PubMed

    Zhang, Luzhong; Li, Guicai; Gao, Ming; Liu, Xin; Ji, Bing; Hua, Ruheng; Zhou, Youlang; Yang, Yumin

    2016-08-01

    Recently, chemotherapy-based polymeric nanoparticles have been extensively investigated for solid tumor treatment. Tumor targeted nanoparticles demonstrated great potential for improved accumulation in the tumor tissue, superior anticancer activity and reduced side effects. Thus, inulin-ibuprofen polymer was synthesized by esterification between inulin and ibuprofen, and RGD targeted epirubicin (EPB) loaded nanoparticles were prepared by the self-assembly of inulin-ibuprofen polymer and in situ encapsulation of EPB. RGD conjugated EPB loaded nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The EPB release from the nanoparticles showed pH-dependent profile and accelerated by the decreased pH value, which would favor the effective drug delivery in vivo. Intracellular uptake analysis suggested that RGD conjugated nanoparticles could be easily internalized by the cancer cells. In vitro cytotoxicity revealed that RGD conjugated EPB loaded nanoparticles exhibited the better antitumor efficacy compared with non-conjugated nanoparticles. More importantly, RGD conjugated EPB loaded nanoparticles showed superior anticancer effects and reduced toxicity than free EPB and non-conjugated nanoparticles by in vivo antitumor activity, EPB biodistribution and histology analysis.

  17. 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)

  18. 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)

  19. 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)

  20. 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.

  1. Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity.

    PubMed Central

    Kinnula, K.; Linnainmaa, K.; Raivio, K. O.; Kinnula, V. L.

    1998-01-01

    We have previously shown that cultured malignant mesothelioma cells contain elevated manganese superoxide dismutase (MnSOD) mRNA levels and activities compared with non-malignant mesothelial cells. As many cytotoxic drugs generate both superoxide and hydrogen peroxide, we assessed the relative significance of catalase and the glutathione redox cycle, as well as glutathione S-transferase (GST), in protecting these cells against hydrogen peroxide and epirubicin toxicity. Mesothelioma cell lines containing high (M38K cells) and low (M14K cells) MnSOD, and non-malignant MeT-5A mesothelial cells were selected for the study. M38K cells were the most resistant of these three cell types to hydrogen peroxide (0.1-0.5 mM, 4 h) and epirubicin (0.1-0.5 microg ml(-1), 48 h) as judged by lactate dehydrogenase (LDH) release and by high-energy nucleotide (ATP, ADP, AMP) depletion. Total glutathione was higher in M38K cells (63.8 +/- 20.3 nnmol mg(-1) protein) than in M14K (25.2 +/- 8.2 nmol mg[-1]) or MeT-5A cells (23.5 +/- 4.5 nmol mg[-1]). Furthermore, GST specific activity was higher in M38K cells (111.3 +/- 15.8 U mg[-1]) than in M14K cells (77.4 +/- 6.6 U mg[-1]) or in MeT-5A cells (68.8 +/- 7.6 U mg[-1]). Western blotting indicated the presence of GST-pi in all these cells, the reactivity again being highest in M38K cells. Depletion of glutathione by buthionine sulphoximine and inhibition of catalase by aminotriazole enhanced hydrogen peroxide toxicity in all cell types, while only the depletion of glutathione increased epirubicin toxicity. We conclude that simultaneous induction of multiple antioxidant enzymes can occur in human mesothelioma cells. In addition to the high MnSOD activity, hydrogen peroxide scavenging antioxidant enzymes, glutathione and GST can partly explain the high hydrogen peroxide and epirubicin resistance of these cells in vitro. Images Figure 4 PMID:9569045

  2. 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.

  3. Epirubicin loaded with propylene glycol liposomes significantly overcomes multidrug resistance in breast cancer.

    PubMed

    Zhao, Ying-Zheng; Dai, Dan-Dan; Lu, Cui-Tao; Chen, Li-Juan; Lin, Min; Shen, Xiao-Tong; Li, Xiao-Kun; Zhang, Ming; Jiang, Xi; Jin, Rong-Rong; Li, Xing; Lv, Hai-Feng; Cai, Lu; Huang, Pin-Tong

    2013-03-01

    Multidrug resistance (MDR) is one of the major reasons for the failure of cancer chemotherapy. A newly reported liposome carrier, propylene glycol liposomes (EPI-PG-liposomes) were made to load epirubicin (EPI) which enhanced EPI absorption in MDR tumor cells to overcome the drug resistance. MDA-MB 435 and their mutant resistant (MDA-MB 435/ADR) cells were used to examine the cellular uptake and P-gp function in vitro for EPI-PG-liposomes by fluorescence microscopy and FCM, respectively. Mammary tumor model was also established to investigate the tumor growth inhibition and pharmacodynamics of EPI-PG-liposomes in vivo. Morphology evaluation showed that EPI-PG-liposomes had a homogeneous spherical shape with an average diameter of 182 nm. Based on cell viability assay, fluorescent microscopy examination, and EPI uptake assay, EPI-PG-liposomes exhibited an effective growth inhibition not only in MDA-MB-435 cells, but also in MDA-MB 435/ADR cells. EPI-PG-liposomes have high permeability not only on tumor cell membrane, but also on cell nucleus membrane. P-gp function assay showed that the anticancer action of EPI-PG-liposomes was not related to P-gp efflux pump, suggesting that PG-liposomes would not affect the normal physiological functions of membrane proteins. EPI-PG-liposomes also showed a better antitumor efficacy compared to EPI solution alone. With high entrapment efficiency, spherical morphology and effective inhibition on MDR cancer cells, EPI-PG-liposomes may represent a better chemotherapeutic vectors for cancer targeted therapy.

  4. The Use of a Liposomal Formulation Incorporating an Antimicrobial Peptide from Tilapia as a New Adjuvant to Epirubicin in Human Squamous Cell Carcinoma and Pluripotent Testicular Embryonic Carcinoma Cells.

    PubMed

    Lo, Yu-Li; Lee, Hsin-Pin; Tu, Wei-Chen

    2015-09-18

    This study aims to explore the effects and mechanisms of hepcidin, a potential antimicrobial peptide from Tilapia, and epirubicin (Epi), an antineoplastic agent, on the generation of reactive oxygen species (ROS) and link the ROS levels to the reversal mechanisms of multidrug resistance (MDR) by epirubicin and hepcidin in human squamous cell carcinoma SCC15 and human embryonal carcinoma NT2D1 cells. The cells, pretreated with hepcidin, epirubicin, or a combination of these compounds in PEGylated liposomes, were used to validate the molecular mechanisms involved in inhibiting efflux transporters and inducing apoptosis as evaluated by cytotoxicity, intracellular accumulation, mRNA levels, cell cycle distribution, and caspase activity of this combination. We found that hepcidin significantly enhanced the cytotoxicity of epirubicin in liposomes. The co-incubation of epirubicin with hepcidin in liposomes intensified the ROS production, including hydrogen peroxide and superoxide free radicals. Hepcidin significantly increased epirubicin intracellular uptake into NT2D1 and SCC15 cells, as supported by the diminished mRNA expressions of MDR1, MDR-associated protein (MRP) 1, and MRP2. Hepcidin and/or epirubicin in liposomes triggered apoptosis, as verified by the reduced mitochondrial membrane potential, increased sub-G1 phase of cell cycle, incremental populations of apoptosis using annexin V/PI assay, and chromatin condensation. As far as we know, this is the first example showing that PEGylated liposomal TH1-5 and epirubicin gives rise to cell death in human squamous carcinoma and testicular embryonic carcinoma cells through the reduced epirubicin efflux via ROS-mediated suppression of P-gp and MRPs and concomitant initiation of mitochondrial apoptosis pathway. Hence, hepcidin in PEGylated liposomes may function as an adjuvant to anticancer drugs, thus demonstrating a novel strategy for reversing MDR.

  5. [Safety and Tolerance of Dose-Dense Epirubicin and Cyclophosphamide (EC) with Pegfilgrastim for Japanese Patients with Early Breast Cancer].

    PubMed

    Watanabe, Kenichi; Sato, Masako; Yamamoto, Mitsugu; Ikarashi, Mayuko; Hagio, Kanako; Tomioka, Nobumoto; Tamaki, Shinya; Takahashi, Yumi; Takahasi, Masato

    2016-04-01

    With the approval of pegfilgrastim, the use of dose-dense epirubicin and cyclophosphamide (EC) for breast cancer has become acceptable in Japan. Thus, we aimed to evaluate its safety and tolerability in Japanese patients. Nine breast cancer patients with a high risk of preoperative or postoperative recurrence received EC therapy(epirubicin 90 mg/m(2) and cyclo- phosphamide 600 mg/m(2))for 4 cycles every 2 weeks in combination with a subcutaneous injection of pegfilgrastim (3.6 mg) on day 2 of each cycle. Treatment was discontinued in 1 and extended in 1 of the 9 patients, and the mean relative dose intensity(RDI)was good at 0.93. No serious adverse events were observed, indicating good tolerability. The regimen has potential for use in cases in which the treatment dose needs to be increased. grade 4 neutropenia was observed in all the 9 patients on day 8, with 6 patients developing febrile neutropenia. In Japan, data on changes in neutrophil count associated with pegfilgrastim administration under anthracycline-based chemotherapy are currently insufficient, and further study is required.

  6. 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.

  7. 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.

  8. Cationic PEGylated liposomes incorporating an antimicrobial peptide tilapia hepcidin 2-3: an adjuvant of epirubicin to overcome multidrug resistance in cervical cancer cells.

    PubMed

    Juang, Vivian; Lee, Hsin-Pin; Lin, Anya Maan-Yuh; Lo, Yu-Li

    Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2-3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2-3 significantly increased the cytotoxicity of epirubicin. The liposomal formulations of epirubicin and/or hepcidin 2-3 were found to noticeably escalate the intracellular H2O2 and O2(-) levels of cancer cells. Furthermore, these treatments considerably reduced the mRNA expressions of MDR protein 1, MDR-associated protein (MRP) 1, and MRP2. The addition of hepcidin 2-3 in liposomes was shown to markedly enhance the intracellular epirubicin uptake and mainly localized into the nucleus. Moreover, this formulation was also found to trigger apoptosis and autophagy in HeLa cells, as validated by significant increases in the expressions of cleaved poly ADP ribose polymerase, caspase-3, caspase-9, and light chain 3 (LC3)-II, as well as a decrease in mitochondrial membrane potential. The apoptosis induction was also confirmed by the rise in sub-G1 phase of cell cycle assay and apoptosis percentage of annexin V/propidium iodide assay. We found that liposomal epirubicin and hepcidin 2-3 augmented the accumulation of GFP-LC3 puncta as amplified by chloroquine, implying the involvement of autophagy. Interestingly, the partial inhibition of necroptosis and the epithelial-mesenchymal transition by this combination was also verified. Altogether, our results provide evidence that coincubation with PEGylated liposomes of hepcidin 2-3 and epirubicin caused programmed cell death in cervical cancer cells through modulation of multiple signaling pathways, including MDR transporters, apoptosis, autophagy, and/or necroptosis

  9. Cationic PEGylated liposomes incorporating an antimicrobial peptide tilapia hepcidin 2–3: an adjuvant of epirubicin to overcome multidrug resistance in cervical cancer cells

    PubMed Central

    Juang, Vivian; Lee, Hsin-Pin; Lin, Anya Maan-Yuh; Lo, Yu-Li

    2016-01-01

    Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2–3, an AMP, as a multidrug resistance (MDR) transporter suppressor and an apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2–3 significantly increased the cytotoxicity of epirubicin. The liposomal formulations of epirubicin and/or hepcidin 2–3 were found to noticeably escalate the intracellular H2O2 and O2− levels of cancer cells. Furthermore, these treatments considerably reduced the mRNA expressions of MDR protein 1, MDR-associated protein (MRP) 1, and MRP2. The addition of hepcidin 2–3 in liposomes was shown to markedly enhance the intracellular epirubicin uptake and mainly localized into the nucleus. Moreover, this formulation was also found to trigger apoptosis and autophagy in HeLa cells, as validated by significant increases in the expressions of cleaved poly ADP ribose polymerase, caspase-3, caspase-9, and light chain 3 (LC3)-II, as well as a decrease in mitochondrial membrane potential. The apoptosis induction was also confirmed by the rise in sub-G1 phase of cell cycle assay and apoptosis percentage of annexin V/propidium iodide assay. We found that liposomal epirubicin and hepcidin 2–3 augmented the accumulation of GFP-LC3 puncta as amplified by chloroquine, implying the involvement of autophagy. Interestingly, the partial inhibition of necroptosis and the epithelial–mesenchymal transition by this combination was also verified. Altogether, our results provide evidence that coincubation with PEGylated liposomes of hepcidin 2–3 and epirubicin caused programmed cell death in cervical cancer cells through modulation of multiple signaling pathways, including MDR transporters, apoptosis, autophagy, and

  10. 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

  11. Pharmacokinetic characterization of amrubicin cardiac safety in an ex vivo human myocardial strip model. II. Amrubicin shows metabolic advantages over doxorubicin and epirubicin.

    PubMed

    Salvatorelli, Emanuela; Menna, Pierantonio; Gonzalez Paz, Odalys; Surapaneni, Sekhar; Aukerman, Sharon L; Chello, Massimo; Covino, Elvio; Sung, Victoria; Minotti, Giorgio

    2012-05-01

    Anthracycline-related cardiotoxicity correlates with cardiac anthracycline accumulation and bioactivation to secondary alcohol metabolites or reactive oxygen species (ROS), such as superoxide anion (O₂·⁻) and hydrogen peroxide H₂O₂). We reported that in an ex vivo human myocardial strip model, 3 or 10 μM amrubicin [(7S,9S)-9-acetyl-9-amino-7-[(2-deoxy-β-D-erythro-pentopyranosyl)oxy]-7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-napthacenedione hydrochloride] accumulated to a lower level compared with equimolar doxorubicin or epirubicin (J Pharmacol Exp Ther 341:464-473, 2012). We have characterized how amrubicin converted to ROS or secondary alcohol metabolite in comparison with doxorubicin (that formed both toxic species) or epirubicin (that lacked ROS formation and showed an impaired conversion to alcohol metabolite). Amrubicin and doxorubicin partitioned to mitochondria and caused similar elevations of H₂O₂, but the mechanisms of H₂O₂ formation were different. Amrubicin produced H₂O₂ by enzymatic reduction-oxidation of its quinone moiety, whereas doxorubicin acted by inducing mitochondrial uncoupling. Moreover, mitochondrial aconitase assays showed that 3 μM amrubicin caused an O₂·⁻-dependent reversible inactivation, whereas doxorubicin always caused an irreversible inactivation. Low concentrations of amrubicin therefore proved similar to epirubicin in sparing mitochondrial aconitase from irreversible inactivation. The soluble fraction of human myocardial strips converted doxorubicin and epirubicin to secondary alcohol metabolites that irreversibly inactivated cytoplasmic aconitase; in contrast, strips exposed to amrubicin failed to generate its secondary alcohol metabolite, amrubicinol, and only occasionally exhibited an irreversible inactivation of cytoplasmic aconitase. This was caused by competing pathways that favored formation and complete or near-to-complete elimination of 9-deaminoamrubicinol. These results characterize amrubicin

  12. Neoadjuvant chemotherapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and docetaxel.

    PubMed

    Gu, Xi; Jia, Shi; Wei, Wei; Zhang, Wen-Hai

    2015-07-01

    Breast cancers (BC) are treated with surgery, radiotherapy, and chemotherapy. Neoadjuvant chemotherapy (NACT) is an emerging treatment option in many cancers and is given before primary therapy to shrink tumor size. The efficacy of NACT in varied settings of BC, such as inoperable tumors, borderline resectable tumors, and breast-conserving surgery, has been debated extensively in literature, and the results remain unclear and depended on a wide variety of factors such as cancer type, disease extent, and the specific combination of chemotherapy drugs. This study was performed to examine the efficacy, toxicity, and tolerability of pirarubicin (THP) and epirubicin (EPI) in combination with docetaxel and cyclophosphamide in a NACT setting for BC. A total of 48 patients with stage II or III breast cancers were randomly divided into two groups: THP group and EPI group. The patients in THP group received 2-4 cycles of neoadjuvant chemotherapy with DTC regimen (docetaxel, THP, cyclophosphamide), while patients in the EPI group received 2-4 cycles of DEC regimen (docetaxel, EPI, cyclophosphamide) before surgery. The incidence of adverse reactions and the efficacy of the treatment regimen were compared between the two groups. Prognostic evaluation indexes were estimated by Kaplan-Meier survival analysis, including the 5-year disease-free survival (DFS) and overall survival (OS). The overall response rate in THP group was 83.3 %, and the EPI group showed a response rate of 79.2 %, with no statistically significant difference in response rate between the two groups. The incidence of cardiac toxicity, myelosuppression, nausea, and vomiting in the THP group was significantly lower than the EPI group (all P < 0.05). The incidence of hepatic toxicity, alopecia, and diarrhea in the THP group was also lower than the EPI group, but these differences were not statistically significant. The 5-year DFS and OS in THP versus EPI groups were 80 versus 76 % (DFS) and 86 versus 81 % (OS

  13. [Binding of epirubicin to human plasma protein and erythrocytes: interaction with the cytoprotective amifostine].

    PubMed

    Pernkopf, I; Tesch, G; Dempe, K; Kletzl, H; Schüller, J; Czejka, M

    1996-11-01

    The in vitro binding rate of epirubicin (EPR) to different plasma proteins, control serum, red blood cells and whole blood was investigated without and with the cytoprotective agent amifostine. The binding rate of EPR to plasma proteins fractions and red blood cells dependend on the concentration of the matrix components. EPR was bound more than 90% to human serum alpha-globulin (alpha-HSG), to human serum albumine (HSA) and human serum beta-globuline (beta-HSG) at 80 to 90%, in the case of human serum gamma-globulin (gamma-HSG) the binding rate amounted 75%. The binding rate of EPR to RBCs in whole blood samples reached 38%. Within the observed concentration range of proteins (1-40 micrograms/ml, depending on the protein concentration) AMI caused a reduction of the protein-bound amount of EPR in the range from 2 to 19% of HSA, 4 to 20 in the case of beta-HSG, 2 to 32% in the case of alpha-HSG and 17 to 21% for gamma-HSG. In the whole blood samples the binding of EPR to proteins dropped from 45 to 32% and RBC-partitioning from 38 to 32%. Two compounds with free thiol groups, cystein and glutathione, were compared with AMI in regard to lowering the binding rate of EPR to HSA: the effect was exactly in the same order of magnitude: -17% for AMI, -21.0% for cystein and -20.8% for glutahion (p < 0.002). For a negative control, cystin and phenylalanin were tested, too: both compounds showed no influence on the protein binding of EPR: 63.8% binding rate in the control group, 65.2% in the presence of cystin and 64.6% in the presence of phenylalanin (statistically not significant). The present results indicate, that binding of EPR to serum proteins is reduced in the presence of AMI by interaction of the thiol-group with the protein and that the thiophosphoric ester bond in the test solution must cleave rapidly.

  14. Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study.

    PubMed

    Martín, Miguel; Ruiz Simón, Amparo; Ruiz Borrego, Manuel; Ribelles, Nuria; Rodríguez-Lescure, Álvaro; Muñoz-Mateu, Montserrat; González, Sonia; Margelí Vila, Mireia; Barnadas, Agustí; Ramos, Manuel; Del Barco Berron, Sonia; Jara, Carlos; Calvo, Lourdes; Martínez-Jáñez, Noelia; Mendiola Fernández, César; Rodríguez, César A; Martínez de Dueñas, Eduardo; Andrés, Raquel; Plazaola, Arrate; de la Haba-Rodríguez, Juan; López-Vega, Jose Manuel; Adrover, Encarna; Ballesteros, Ana Isabel; Santaballa, Ana; Sánchez-Rovira, Pedro; Baena-Cañada, José M; Casas, Maribel; del Carmen Cámara, María; Carrasco, Eva Maria; Lluch, Ana

    2015-11-10

    Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC. Patients with operable node-positive BC (T1-3/N1-3) were eligible. After surgery, 1,384 patients were randomly assigned to receive epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m(2), respectively, × four cycles), followed by docetaxel (100 mg/m(2) × four cycles; EC-T) or epirubicin plus docetaxel (ET; 90 and 75 mg/m(2), respectively, × four cycles), followed by capecitabine (1,250 mg/m(2) twice a day on days 1 to 14, × four cycles; ET-X); all regimens were given every 3 weeks. The primary end point was invasive disease-free survival. Secondary end points included safety (with an alopecia-specific study) and overall survival (OS). After a median follow-up of 6.6 years and 297 events, 86% of patients who received EC-T and 82% of those who received ET-X were invasive disease free at 5 years (hazard ratio, 1.30; 95% CI, 1.03 to 1.64; log-rank P = .03). The OS difference between arms was not statistically significant (hazard ratio, 1.13; 95% CI, 0.82 to 1.55; log-rank P = .46). The most frequent grade 3 to 4 adverse events in the EC-T versus ET-X arms were neutropenia (19% v 10%), with 7% febrile neutropenia across arms; fatigue (13% v 11%); diarrhea (3% v 11%); hand-foot syndrome (2% v 20%); mucositis (6% v 5%); vomiting (both, 5%); and myalgia (4.5% v 1%). Incomplete scalp hair recovery was more frequent in the EC-T than ET-X arm (30% v 14%), and patients who received EC-T wore wigs significantly longer than those who received ET-X (8.35 v 6.03 months). Invasive disease-free survival, but not OS, was significantly superior for patients with node-positive early BC who received the adjuvant standard schedule EC-T than for those who received the experimental ET-X regimen. Toxicity profiles differed substantially across arms. © 2015 by American

  15. 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.

  16. 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, ...

  17. 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.

  18. 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

  19. Compatibility of an Ultraselective Microcatheter and Epirubicin Loaded 300–500-μm DC Bead in Ex Vivo Study

    SciTech Connect

    Fukuoka, Yasushi Tanaka, Toshihiro Nishiofuku, Hideyuki Sato, Takeshi Kichikawa, Kimihiko

    2015-10-15

    PurposeThe purpose of this study is to examine whether epirubicin loaded DC Bead 300–500 μm in size can pass through a 1.8-Fr ultraselective microcatheter in ex vivo study.MethodsEpirubicin (25 mg/1 mL) loaded 100–300 and 300–500 μm DC Bead were tested. Both sizes were diluted 5, 10, and 30 times using contrast material. Ultraselective microcatheter with the outer diameter of 1.8 Fr and the inner diameter of .017 inch (431.8 μm) was used. The diluted DC Bead was injected at a speed of 1 mL/min, and the pressure was continuously measured. The microspheres’ shapes after ejection were observed by a stereomicroscope.ResultsThe maximum pressure of contrast material alone was 8.40 ± 0.21 psi. The maximum pressure in 5, 10, and 30 times dilution groups of 100–300 μm were 9.67 ± 1.18, 9.25 ± 0.25, and 9.71 ± 0.28 psi, respectively, whereas 21.10 ± 10.2, 10.48 ± 2.14, 10.09 ± 0.37 psi, respectively in 300–500 μm groups. The maximum pressure in 5 times dilution group of 300–500 μm was significantly higher than the other groups (P < 0.05). In 300–500 μm, 4 of 10 measurements showed high pressure over 24 psi (the maximum value was 43.5 psi) in 5 times dilution group, whereas in 10 times and 30 times dilution groups, all measurements showed less than 12 psi. No damages of microspheres were found.ConclusionsEpirubicin loaded DC Bead 300–500 μm in size can pass through a 1.8-Fr ultraselective microcatheter. To avoid high resistance due to microspheres’ aggregation, dilution more than 10 times is needed.

  20. 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.

  1. Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer

    PubMed Central

    Zhang, Minmin; Wei, Wei; Liu, Jianlun; Yang, Huawei; Jiang, Yi; Tang, Wei; Li, Qiuyun; Liao, Xiaoming

    2016-01-01

    The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4–6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively. PMID:27354816

  2. 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.

  3. [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.

  4. Biological monitoring of nurses exposed to doxorubicin and epirubicin by a validated liquid chromatography/fluorescence detection method.

    PubMed

    Pieri, Maria; Castiglia, Loredana; Basilicata, Pascale; Sannolo, Nicola; Acampora, Antonio; Miraglia, Nadia

    2010-06-01

    Occupational exposure to antineoplastic drugs can represent a potential health risk for hospital staff. Assessing exposure is the first step in providing a safe work environment; the present study aimed to perform a biological monitoring (BM) of nurses exposed to doxorubicin and epirubicin. In order to assure data accuracy and reproducibility, the high-performance liquid chromatography with fluorescence detection method was validated. Validation experiments were carried out according to the Food and Drug Administration guidelines. A detailed questionnaire about workplace practices and work organization was administered to 56 nurses of oncology department of two hospitals (A and B) located in southern Italy. End-shift urine samples were collected. Amounts of drugs handled were registered. The quantification and detection limits were 1.1 and 0.6 pg microl(-1) (doxorubicin) and 2.0 and 1.2 pg microl(-1) (epirubicin); moreover, the analytical method fulfilled all guidelines requirements. Questionnaire information evidenced that vertical laminar flow hoods were present in both hospitals, surfaces were cleaned with inappropriate detergents, no antispilling devices were adopted, and gloves were not changed during the work shift. A lower percentage of positive samples was found in the hospital where higher amounts of anthracyclines were handled (3.4% in A and 14.8% in B), suggesting individual incorrect working/cleaning practices in hospital A and overall hygienic standards to be improved in hospital B, where 'critical practices' were carried out. Results showed the crucial role of adopting effective safety precautions and handling practices to reduce exposure. Environmental and BM should be performed to discriminate between incorrect personal working modalities and general hygienic standards.

  5. Epirubicin loaded super paramagnetic iron oxide nanoparticle-aptamer bioconjugate for combined colon cancer therapy and imaging in vivo.

    PubMed

    Jalalian, Seyed Hamid; Taghdisi, Seyed Mohammad; Shahidi Hamedani, Nasim; Kalat, Seyedeh Alia Moosavian; Lavaee, Parirokh; Zandkarimi, Majid; Ghows, Narjes; Jaafari, Mahmoud Reza; Naghibi, Saeed; Danesh, Noor Mohammad; Ramezani, Mohammad; Abnous, Khalil

    2013-10-09

    Every year a large number of new cases of colorectal cancer are diagnosed in the world. Application of Epirubicin (Epi) in treatment of cancer has been limited due to its cardiotoxicity. Specific delivery of chemotherapy drugs is an important factor in reducing the side effects of drugs used in chemotherapy. Enhanced permeability, retention effect and magnetic resonance (MR) traceability of super paramagnetic iron oxide nanoparticles (SPION) make them a great candidate in cancer therapy and imaging. In this study, Epirubicin-5TR1 aptamer-SPION tertiary complex was evaluated for the imaging and treatment of murine colon carcinoma cells (C26 cells, target). For cytotoxic studies (MTT assay), C26 and CHO-K1 (Chinese hamster ovary cells, nontarget) cells were treated with either Epi or Epi-Apt-SPION tertiary complex. Internalization was evaluated by flow cytometry. Finally, Apt-SPION bioconjugate was used for imaging of cancer in vivo. Flow cytometric analysis showed that the tertiary complex was internalized effectively to C26 cells, but not to CHO-K1 cells. Cytotoxicity of Epi-Apt-SPION tertiary complex also confirmed internalization data. The complex was less cytotoxic in CHO-K1 cells when compared to Epi alone. No significant change in viability between Epi- and complex-treated C26 cells was observed. Magnetic resonance imaging (MRI) indicated a high level of accumulation of the nano-magnets within the tumor site. In conclusion Epi-Apt-SPION tertiary complex is introduced as an effective system for targeted delivery of Epi to C26 cells. Moreover this complex could efficiently detect tumors when analyzed by MRI and inhibit tumor growth in vivo.

  6. Enhanced antitumor effect of anti-tissue factor antibody-conjugated epirubicin-incorporating micelles in xenograft models

    PubMed Central

    Yamamoto, Yoshiyuki; Hyodo, Ichinosuke; Koga, Yoshikatsu; Tsumura, Ryo; Sato, Ryuta; Obonai, Toshihumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Yasunaga, Masahiro; Harada, Mitsunori; Kato, Yasuki; Ohtsu, Atsushi; Matsumura, Yasuhiro

    2015-01-01

    For the creation of a successful antibody–drug conjugate (ADC), both scientific and clinical evidence has indicated that highly toxic anticancer agents (ACA) should be conjugated to a monoclonal antibody (mAb) to administer a reasonable amount of ADC to patients without compromising the affinity of the mAb. For ordinary ACA, the conjugation of a mAb to ACA-loaded micellar nanoparticles is clinically applicable. Tissue factor (TF) is often overexpressed in various cancer cells and tumor vascular endothelium. Accordingly, anti-TF-NC-6300, consisting of epirubicin-incorporating micelles (NC-6300) conjugated with the F(ab')2 of anti-TF mAb was developed. The in vitro and in vivo efficacy and pharmacokinetics of anti-TF-NC-6300 were compared to NC-6300 using two human pancreatic cancer cell lines, BxPC3 (high TF expression) and SUIT2 (low TF expression), and a gastric cancer cell line, 44As3 (high TF expression). The intracellular uptake of epirubicin was faster and greater in BxPC3 cells treated with anti-TF-NC-6300, compared with NC-6300. Anti-TF-NC-6300 showed a superior antitumor activity in BxPC3 and 44As3 xenografts, compared with NC-6300, while the activities of both micelles were similar in the SUIT2 xenograft. A higher tumor accumulation of anti-TF-NC-6300 compared to NC-6300 was seen, regardless of the TF expression levels. However, anti-TF-NC-6300 appeared to be localized to the tumor cells with high TF expression. These results indicated that the enhanced antitumor effect of anti-TF-NC6300 may be independent of the tumor accumulation but may depend on the selective intratumor localization and the preferential internalization of anti-TF-NC-6300 into high TF tumor cells. PMID:25711681

  7. Enhanced antitumor effect of anti-tissue factor antibody-conjugated epirubicin-incorporating micelles in xenograft models.

    PubMed

    Yamamoto, Yoshiyuki; Hyodo, Ichinosuke; Koga, Yoshikatsu; Tsumura, Ryo; Sato, Ryuta; Obonai, Toshihumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Yasunaga, Masahiro; Harada, Mitsunori; Kato, Yasuki; Ohtsu, Atsushi; Matsumura, Yasuhiro

    2015-05-01

    For the creation of a successful antibody-drug conjugate (ADC), both scientific and clinical evidence has indicated that highly toxic anticancer agents (ACA) should be conjugated to a monoclonal antibody (mAb) to administer a reasonable amount of ADC to patients without compromising the affinity of the mAb. For ordinary ACA, the conjugation of a mAb to ACA-loaded micellar nanoparticles is clinically applicable. Tissue factor (TF) is often overexpressed in various cancer cells and tumor vascular endothelium. Accordingly, anti-TF-NC-6300, consisting of epirubicin-incorporating micelles (NC-6300) conjugated with the F(ab')2 of anti-TF mAb was developed. The in vitro and in vivo efficacy and pharmacokinetics of anti-TF-NC-6300 were compared to NC-6300 using two human pancreatic cancer cell lines, BxPC3 (high TF expression) and SUIT2 (low TF expression), and a gastric cancer cell line, 44As3 (high TF expression). The intracellular uptake of epirubicin was faster and greater in BxPC3 cells treated with anti-TF-NC-6300, compared with NC-6300. Anti-TF-NC-6300 showed a superior antitumor activity in BxPC3 and 44As3 xenografts, compared with NC-6300, while the activities of both micelles were similar in the SUIT2 xenograft. A higher tumor accumulation of anti-TF-NC-6300 compared to NC-6300 was seen, regardless of the TF expression levels. However, anti-TF-NC-6300 appeared to be localized to the tumor cells with high TF expression. These results indicated that the enhanced antitumor effect of anti-TF-NC6300 may be independent of the tumor accumulation but may depend on the selective intratumor localization and the preferential internalization of anti-TF-NC-6300 into high TF tumor cells. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  8. [Epirubicin-based combination chemotherapy combined with G-CSF for the elderly patients with non-Hodgkin's lymphoma].

    PubMed

    Miyata, A; Fujii, S; Kikuchi, T; Kibata, M

    2000-02-01

    We devised a new epirubicin-based combination chemotherapy (Epi-COP) regimen for the patients with elderly non-Hodgkin's lymphoma and have treated 30 patients aged 66 years and older who had measurable diseases. In Epi-COP therapy, epirubicin was used as a substitute for doxorubicin in the CHOP regimen, and some dose modifications were made for the other agents. Combined modality treatment (CMT; chemotherapy plus radiotherapy) was adopted for 9 patients with localized disease. Complete response was obtained in 21 of all the 30 patients (70%), 8 in 9 (89%) of the CMT group and 13 in 21 (62%) of the patients with chemotherapy only (chemotherapy group). The median follow up time is 350 days, ranging from 2 to 77 months. The 2 year survival rate was 56% in all patients, 67% in the CMT group and 52% in the chemotherapy group. Granulocyte colony-stimulating factor (G-CSF) was administered when the leucocyte count decreased below 2,000/microliter, and 16 patients received it in the first course. The regimen could be repeated every three weeks in most cases. Although we encountered two early deaths, the overall toxicity level seemed to be acceptable. Even when we take account of the small number of patients and the short observation period, it might be concluded that Epi-COP was effective in inducing a good remission rate with moderate toxic effect in elderly patients with non-Hodgkin's lymphoma and CMT should be adopted if it is localized. A randomized comparative study with the CHOP regimen is necessary.

  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. 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.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Feasibility and safety of weekly sequential epirubicin-paclitaxel as adjuvant treatment for operable breast cancer patients older than 70 years.

    PubMed

    Ladoire, Sylvain; Rambach, Laurie; Quipourt, Valérie; Favier, Laure; Ghiringhelli, François; Arnould, Laurent; Pfitzenmeyer, Pierre; Fumoleau, Pierre; Coudert, Bruno

    2011-08-01

    There are currently no internationally agreed recommendations for the management of adjuvant chemotherapy in women aged >70 years with high-risk breast cancer. The purpose of this study was to assess the feasibility and the tolerance of adjuvant weekly sequential epirubicin-paclitaxel combination in this setting. From 2005 to 2009, 59 women over 70 years of age with operable breast cancer and who required adjuvant chemotherapy were proposed weekly sequential epirubicin-paclitaxel chemotherapy schedule, and were prospectively registered. Compliance and treatment tolerance were studied. We also report preliminary results of disease-free survival (DFS) and overall survival (OS). Weekly sequential epirubicin-paclitaxel was well tolerated. No grade 4 adverse event occurred. No secondary malignancy was observed. Compliance with chemotherapy was good: 95% of patients received the six planned cycles. After a median follow-up of 24 months, median DFS and OS were not reached, there were only three relapses, and two cancer-related deaths were reported. This study conducted in patients over 70 years of age demonstrates the feasibility of weekly adjuvant chemotherapy including anthracyclines and taxanes in a sequential schedule. This regimen is safe in terms of hematologic, nonhematologic, and cardiac toxicities, and showed encouraging efficacy, justifying further studies in geriatric patients. Copyright © 2011. Published by Elsevier Inc.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification.

    PubMed

    Tarpgaard, Line S; Qvortrup, Camilla; Nygård, Sune B; Nielsen, Signe L; Andersen, Diana R; Jensen, Niels Frank; Stenvang, Jan; Detlefsen, Sönke; Brünner, Nils; Pfeiffer, Per

    2016-02-11

    The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2A gene amplification in their tumor cells. Epirubicin is an anthracycline that targets DNA topoisomerase 2-α enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC. TOP2A gene amplifications predict improved efficacy of epirubicin in patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6% of these tumors had TOP2A copy gain and 2.0% had loss of TOP2A when compared to adjacent normal tissue. The TOP2A gene is located on chromosome 17 and when the TOP2A/CEN-17 ratio was applied to identify tumors with gene loss or amplifications, 10.5% had a ratio ≥ 1.5 consistent with gene amplification and 2.6% had a ratio ≤ 0.8 suggesting gene deletions. Based on these observations and the knowledge gained from treatment of breast cancer patients, we have initiated a prospective clinical, phase II protocol using epirubicin (90 mg/m2 iv q 3 weeks) in mCRC patients, who are refractory to treatment with oxaliplatin. The study is an open label, single arm, phase II study, investigating the efficacy of epirubicin in patients with oxaliplatin refractory mCRC and with a cancer cell TOP2A/CEN-17 ratio ≥ 1.5. TOP2A gene amplification measured by fluorescence in situ hybridization. A total of 25 evaluable patients (15 + 10 in two steps) will be included (Simon's two-stage minimax design). Every nine weeks, response is measured by computed tomography imaging and evaluated according to RECIST 1.1. The primary end-point of the study is progression-free survival. Eudract no. 2013-001648-79.

  5. 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

  6. 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.

  7. Objective Measurement of Arterial Flow Before and After Transcatheter Arterial Chemoembolization: A Feasibility Study Using Quantitative Color-Coding Analysis.

    PubMed

    Lin, Yi-Yang; Lee, Rheun-Chuan; Tseng, Hsiuo-Shan; Liu, Chien-An; Guo, Wan-Yuo; Chang, Cheng-Yen

    2015-12-01

    To quantitatively measure the hemodynamic change of hepatic artery before and after transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) by quantitative color-coding analysis (QCA). This prospective study registered 64 consecutive HCC patients who underwent segmental or subsegmental TACE with epirubicin and lipiodol at level 2 or 3 of the subjective angiographic chemoembolization endpoint. QCA was used to determine the maximal density time (T(max)) of selected intravascular region of interest (ROI). Relative T(max) (rT(max)) was defined as the T(max) at the selected ROI minus the time of contrast medium spurting from the catheter tip. The rT(max) of hepatic arteries was analyzed before and after embolization. The pre- and post-treatment rT(max) of the landmarks at the treated segmental artery were 1.96 ± 0.48 and 3.14 ± 1.77 s, p < 0.001. According to the treated lobe, 30 patients were treated for the right lobe alone, and 8 patients were treated for the left lobe alone. The pre- and post-rT(max) of treated segmental artery were 2.06 ± 0.54, 3.34 ± 1.63 s, p < 0.001 and 1.89 ± 0.45, 2.68 ± 1.46 s, p = 0.12, respectively. The rT(max) of the proximal lobar hepatic arteries or proper hepatic artery had no significant change before and after TACE. The QCA is feasible to quantify embolization endpoints by comparing the rT(max) in selected hepatic arteries before and after TACE. The rT(max) of treated segmental artery was significant prolonged after optimized procedures.

  8. [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.

  9. 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

  10. Epirubicin-loaded superparamagnetic iron-oxide nanoparticles for transdermal delivery: cancer therapy by circumventing the skin barrier.

    PubMed

    Rao, Yue-feng; Chen, Wei; Liang, Xing-guang; Huang, Yong-zhuo; Miao, Jing; Liu, Lin; Lou, Yan; Zhang, Xing-guo; Wang, Ben; Tang, Rui-kang; Chen, Zhong; Lu, Xiao-yang

    2015-01-14

    The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They feature specific pH-sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose-dependent. In vitro transdermal studies demonstrate that the EPI-SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Cost-effectiveness Analysis of Fluorouracil, Leucovorin, and Irinotecan versus Epirubicin, Cisplatin, and Capecitabine in Patients with Advanced Gastric Adenocarcinoma

    PubMed Central

    Wen, Feng; Zheng, Hanrui; Wu, Yifan; Wheeler, John; Zeng, Xiaoxi; Fu, Ping; Li, Qiu

    2016-01-01

    No standard treatment has been accepted widely for the first-/second-line therapy for advanced gastric cancer (AGC). The current study aimed to determine a preferred strategy between FOLFIRI (fluorouracil, leucovorin, and irinotecan) and ECX (epirubicin, cisplatin,and capecitabine) for AGC from the cost-effectiveness perspective. According to a French intergroup study, two groups (ECX arm and FOLFIRI arm) and three health states (progression-free survival (PFS), progressive disease (PD) and death) were analyzed in the current Markov model. All the medical costs were calculated from a Chinese societal perspective. Although FOLFIRI was an acceptable first-line therapy in the treatment of AGC with a better time-to treatment failure (TTF) compared to ECX, ECX arm (ECX followed by FOLFIRI) gained 0.08 quality-adjusted life months (QALMs) more effectiveness benefit compared with FOLFIRI arm (FOLFIRI followed by ECX). Additionally, a lower cost was found in ECX arm ($23,813.13 versus $24,983.70). Hence, the strategy of FOLFIRI arm is dominated by ECX arm ($4,125.8 per QALM in FOLIRI arm; $3,879.724 per QALM in ECX arm). ECX followed by FOLFIRI was a preferred strategy with more effectiveness and lower cost compared with FOLFIRI followed by ECX for the treatment of AGC. PMID:27824060

  12. Inhibition of N-Terminal Lysines Acetylation and Transcription Factor Assembly by Epirubicin Induced Deranged Cell Homeostasis

    PubMed Central

    Khan, Shahper N.; Danishuddin, Mohd; Varshney, Bhavna; Lal, Sunil K.; Khan, Asad U.

    2012-01-01

    Epirubicin (EPI), an anthracycline antitumour antibiotic, is a known intercalating and DNA damaging agent. Here, we study the molecular interaction of EPI with histones and other cellular targets. EPI binding with histone core protein was predicted with spectroscopic and computational techniques. The molecular distance r, between donor (histone H3) and acceptor (EPI) was estimated using Förster’s theory of non-radiation energy transfer and the detailed binding phenomenon is expounded. Interestingly, the concentration dependent reduction in the acetylated states of histone H3 K9/K14 was observed suggesting more repressed chromatin state on EPI treatment. Its binding site near N-terminal lysines is further characterized by thermodynamic determinants and molecular docking studies. Specific DNA binding and inhibition of transcription factor (Tf)-DNA complex formation implicates EPI induced transcriptional inhibition. EPI also showed significant cell cycle arrest in drug treated cells. Chromatin fragmentation and loss of membrane integrity in EPI treated cells is suggestive of their commitment to cell death. This study provides an analysis of nucleosome dynamics during EPI treatment and provides a novel insight into its action. PMID:23251640

  13. Sonodynamic Therapy Based on Combined Use of Low Dose Administration of Epirubicin-Incorporating Drug Delivery System and Focused Ultrasound.

    PubMed

    Maeda, Masanori; Muragaki, Yoshihiro; Okamoto, Jun; Yoshizawa, Shin; Abe, Nobutaka; Nakamoto, Hidekazu; Ishii, Hiroshi; Kawabata, Kenichi; Umemura, Shinichiro; Nishiyama, Nobuhiro; Kataoka, Kazunori; Iseki, Hiroshi

    2017-10-01

    Sonodynamic therapy (SDT) is currently considered as one of the promising minimally invasive treatment options for solid cancers. SDT is based on the combined use of a sonosensitizer drug and high-intensity focused ultrasound (HIFU) to produce cytotoxic reactive oxygen species (ROS) in and around neoplastic cells. Anthracycline drugs, including epirubicin (EPI), have been well known as effective sonosensitizers after interaction with focused ultrasound. Recently a new anticancer drug delivery system (DDS), NC-6300, has been developed that comprises EPI through an acid-labile hydrazone bond. In previous in vivo studies, NC-6300 showed basic drug safety and an excellent concentration property of EPI, and recently has been tested in clinical trials. For realizing minimally invasive cancer treatment, the present study demonstrated the effectiveness and feasibility of DDS-based SDT, which combined a small dose of NC-6300 and low energy of HIFU in mouse models of colon cancer and pancreatic cancer. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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.

  20. 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.

  1. The protective effects of paeonol against epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice via inhibition of the PI3K/Akt/NF-kB pathway.

    PubMed

    Wu, Jing; Xue, Xia; Zhang, Bin; Jiang, Wen; Cao, Hongmei; Wang, Rongmei; Sun, Deqing; Guo, Ruichen

    2016-01-25

    Epirubicin is widely used for the treatment of various breast cancers; however, it has serious adverse side effects, such as hepatotoxicity, which require dose-adjustment or therapy substitution. Paeonol, an active component from Moutan Cortex, has a variety of biological activities, including preventing or reducing various toxicities induced by antineoplastics. Protection by paeonol against hepatotoxicity induced by epirubicin and the underlying mechanism of action were investigated in this study. Cytosolic enzymes in the serum and oxidative stress indices in the liver were determined. The protective effects were determined using the MTT assay in vitro or by evaluating the expression of apoptotic factors and crucial proteins in the PI3K/Akt/NF-kB pathway using western blot analysis. It is concluded that paeonol alleviates epirubicin-induced hepatotoxicity in 4T1-tumor bearing mice by inhibiting the PI3K/Akt/NF-kB pathway.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. Pharmacokinetic characterization of amrubicin cardiac safety in an ex vivo human myocardial strip model. I. Amrubicin accumulates to a lower level than doxorubicin or epirubicin.

    PubMed

    Salvatorelli, Emanuela; Menna, Pierantonio; Surapaneni, Sekhar; Aukerman, Sharon L; Chello, Massimo; Covino, Elvio; Sung, Victoria; Minotti, Giorgio

    2012-05-01

    Antitumor anthracyclines such as doxorubicin and epirubicin are known to cause cardiotoxicity that correlates with anthracycline accumulation in the heart. The anthracycline amrubicin [(7S,9S)-9-acetyl-9-amino-7-[(2-deoxy-β-d-erythro-pentopyranosyl)oxy]-7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-napthacenedione hydrochloride] has not shown cardiotoxicity in laboratory animals or patients in approved or investigational settings; therefore, we conducted preclinical work to characterize whether amrubicin attained lower levels than doxorubicin or epirubicin in the heart. Anthracyclines were evaluated in ex vivo human myocardial strips incubated in plasma to which anthracycline concentrations of 3 or 10 μM were added. Four-hour incubations were performed to characterize myocardial anthracycline accumulation derived from anthracycline uptake in equilibrium with anthracycline clearance. Short-term incubations followed by multiple washouts were performed to obtain independent measurements of anthracycline uptake or clearance. In comparison with doxorubicin or epirubicin, amrubicin attained very low levels in the soluble and membrane fractions of human myocardial strips. This occurred at both 3 and 10 μM anthracycline concentrations and was caused primarily by a highly favorable clearance of amrubicin. Amrubicin clearance was facilitated by formation and elimination of sizeable levels of 9-deaminoamrubicin and 9-deaminoamrubicinol. Amrubicin clearance was not mediated by P glycoprotein or other drug efflux pumps, as judged from the lack of effect of verapamil on the partitioning of amrubicin and its deaminated metabolites across myocardial strips and plasma. Limited accumulation of amrubicin in an ex vivo human myocardial strip model may therefore correlate with the improved cardiac tolerability observed with the use of amrubicin in preclinical or clinical settings.

  12. 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.

  13. Evaluation of the tracing effect of carbon nanoparticle and carbon nanoparticle-epirubicin suspension in axillary lymph node dissection for breast cancer treatment.

    PubMed

    Du, Junze; Zhang, Yongsong; Ming, Jia; Liu, Jing; Zhong, Ling; Liang, Quankun; Fan, Linjun; Jiang, Jun

    2016-06-22

    Carbon nanoparticle suspension, using smooth carbon particles at a diameter of 21 nm added with suspending agents, is a stable suspension of carbon pellets of 150 nm in diameter. It is obviously inclined to the lymphatic system. There were some studies reporting that carbon nanoparticles are considered as superior tracers for sentinel lymph nodes because of their stability and operational feasibility. However, there were few study concerns about the potential treatment effect including tracing and local chemotherapeutic effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. In the current study, a randomized controlled analysis was performed to investigate the potential treatment effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. A total of 90 breast cancer patients were randomly divided into three equal groups: control, tracer, and drug-load groups. The control group patients did not receive any lymphatic tracers, the tracer group patients were subcutaneously injected with 1 ml carbon nanoparticle suspension, and the drug-load group patients were injected with 3 ml carbon nanoparticle-epirubicin suspension at four separate sites around the areola 24 h before surgery. Modified radical mastectomy, endoscopic subcutaneous mammary resection plus axillary lymph node dissection, and immediate reconstruction with implants or breast-conserving surgery were performed. The mean number of the dissected lymph nodes per patient was significantly higher in the tracer (21.3 ± 6.1) and drug-load (19.5 ± 3.7) groups than in the control group (16.7 ± 3.4) (P < 0.05). Most lymph nodes in the former two groups were stained black (75.7 and 73.3 %, respectively), but with no significant difference between the groups. Most metastatic lymph nodes were also stained black in the tracer group (68.6 %) and drug-load group (78.1 %) and with no significant difference between the

  14. 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 ...

  15. 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.

  16. 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.

  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. Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.

    PubMed

    Bertheau, Philippe; Turpin, Elisabeth; Rickman, David S; Espié, Marc; de Reyniès, Aurélien; Feugeas, Jean-Paul; Plassa, Louis-François; Soliman, Hany; Varna, Mariana; de Roquancourt, Anne; Lehmann-Che, Jacqueline; Beuzard, Yves; Marty, Michel; Misset, Jean-Louis; Janin, Anne; de Thé, Hugues

    2007-03-01

    In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown. In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile

  19. Postoperative CMF Does Not Ameliorate Poor Outcomes in Women With Residual Invasive Breast Cancer After Neoadjuvant Epirubicin/Docetaxel Chemotherapy.

    PubMed

    Promberger, Regina; Dubsky, Peter; Mittlböck, Martina; Ott, Johannes; Singer, Christian; Seemann, Rudolf; Exner, Ruth; Panhofer, Peter; Steger, Günther; Bergen, Elisabeth; Gnant, Michael; Jakesz, Raimund; Bago-Horvath, Zsuzsanna; Rudas, Margaretha; Bartsch, Rupert

    2015-12-01

    Neoadjuvant chemotherapy (NACT) is an accepted treatment approach in early-stage breast cancer. In contrast, the potential role of postneoadjuvant chemotherapy after taxane-containing NACT remains unclear. The aim of this study was to evaluate postneoadjuvant chemotherapy and further prognostic factors that predict outcome in women without pathologic complete remission (pCR). A total of 377 patients with breast cancer who received preoperative chemotherapy were included in this retrospective study. Patients without standard NACT (6 cycles of epirubicin with docetaxel) or primary metastatic breast cancer and locally advanced, inoperable cancer were excluded from further analysis (n = 186). This resulted in a study population of 191 women (30 [15.7%] with pCR; 161 [84.3%] without pCR). Major outcome parameters were event-free survival (EFS) and overall survival (OS). The following parameters were tested for their prognostic role: postneoadjuvant chemotherapy, patient age, breast cancer subtype (luminal/HER2-negative tumors, HER2-positive tumors, and triple-negative tumors), histological grade, pCR, residual lymph node invasion, and residual invasive tumor size. At a median follow-up of 54 months, 51 disease relapses (26.7%) and 21 deaths (11%) were observed. In a comparison of patients with pCR with those without, no significant differences in EFS or OS were observed. Postneoadjuvant chemotherapy was significantly associated with shorter OS in patients without pCR. In this population, which included a high percentage of patients with luminal cancers, pCR did not predict for improved OS. Postneoadjuvant chemotherapy showed no discernible benefit even in subgroups with aggressive tumor biology or significant remaining tumor burden. The use of such treatment should therefore be discouraged outside of clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Surface modification of PLGA nanoparticles with biotinylated chitosan for the sustained in vitro release and the enhanced cytotoxicity of epirubicin.

    PubMed

    Chen, Hongli; Xie, Li Qin; Qin, Jingwen; Jia, Yajing; Cai, Xinhua; Nan, WenBin; Yang, Wancai; Lv, Feng; Zhang, Qi Qing

    2016-02-01

    In this study, poly(d,l-lactide-co-glycolide) nanoparticles (PLGA NPs) with biotinylated chitosan (Bio-CS)-surface modification were prepared to be usded as a tumor-targeted and prolonged delivery system for anticancer drugs. Epirubicin (EPB), as a model drug, was encapsulated into Bio-CS surface modified PLGA (Bio-CS-PLGA) NPs with a drug encapsulation efficiency of 84.1 ± 3.4%. EPB-loaded Bio-CS-PLGA NPs were spherical shaped, and had a larger size and higher positive zeta potential compared to the unmodfied EPB-loaded PLGA NPs. The in vitro drug releases showed that EPB-loaded Bio-CS-PLGA NPs exhibited relatively constant drug release kinetics during the first 48 h and the drug burst release significantly decreased in comparison to the unmodified PLGA NPs. The results of MTS assays showed that Bio-CS-PLGA NPs markedly increased the cytotoxicity of EPB, compared to both the unmodified PLGA NPs and the CS-PLGA NPs. The uptakes of NPs in human breast cancer MCF-7 cells were evaluated by the flow cytometry and the confocal microscope. The results revealed that Bio-CS-PLGA NPs exhibited a greater extent of cellular uptake than the unmodified PLGA NPs and CS-PLGA NPs. Moreover, the cellular uptake of Bio-CS-PLGA NPs was evidently inhibited by the endocytic inhibitors and the receptor ligand, indicating that biotin receptor-mediated endocytosis was perhaps involved in the cell entry of Bio-CS-PLGA NPs. In MCF-7 tumor-bearing nude mice, EPB-loaded Bio-CS-PLGA NPs were efficiently accumulated in the tumors. In summary, Bio-CS-PLGA NPs displayed great potential for application as the carriers of anticancer drugs.

  1. Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer.

    PubMed

    Cainap, Calin; Nagy, Viorica; Seicean, Andrada; Gherman, Alexandra; Laszlo, Istvan; Lisencu, Cosmin; Nadim, Al Hajar; Constantin, Anne-Marie; Cainap, Simona

    2016-01-01

    The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj-Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS.

  2. Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis

    PubMed Central

    Sahu, Arvind; Ramaswamy, Anant; Sirohi, Bhawna; Bose, Subhadeep; Talreja, Vikas; Goel, Mahesh; Patkar, Shraddha; Desouza, Ashwin; Shrikhande, Shailesh V.

    2017-01-01

    Purpose Perioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer. Materials and Methods We retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai. Results Among the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival. Conclusions EOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resection, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial. PMID:28337360

  3. 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.

  4. 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

  5. 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

  6. 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. ...

  7. Preexposure of MCF-7 breast cancer cell line to dexamethasone alters the cytotoxic effect of paclitaxel but not 5-fluorouracil or epirubicin chemotherapy

    PubMed Central

    Buxant, Frederic; Kindt, Nadège; Noël, Jean-Christophe; Laurent, Guy; Saussez, Sven

    2017-01-01

    Purpose Glucocorticoids (GCs) are often administered prior to any chemotherapeutics to prevent the secondary effects of anticancer agents. Glucocorticoid receptors (GRs) are expressed in several types of cancer cells, particularly in several histological types of breast cancer. Activation of GRs is not associated with any specific cellular response. Both proapoptotic and antiapoptotic responses have been observed, depending on the study or the type of breast cancer cells. Therefore, it is of relevance to investigate the possible modulation of apoptotic effect of chemotherapeutic agents when cancerous cells have previously been exposed to GCs. Methods In vitro cell growth was assayed by counting MCF-7 cells upon exposure to epirubicin (25 nM), 5-fluorouracil (5-FU) (15 µM), and paclitaxel (15 nM), either with or without prior exposure to the GC dexamethasone (Dex) (100 nM). Results Following preexposure to Dex, the antiapoptotic activity of paclitaxel was significantly reduced by 8.5% (p<0.05), but the activities of epirubicin and 5-FU remained unaltered. Conclusion In light of the finding that the response of MCF-7 cells pretreated with Dex was significantly reduced, we recommend that the function of GCs should be defined more precisely if they are to be used in conjunction with chemotherapy. PMID:28352202

  8. Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats.

    PubMed

    Fan, Chiaming; Georgiou, Kristen R; McKinnon, Ross A; Keefe, Dorothy M K; Howe, Peter R C; Xian, Cory J

    2016-05-01

    The introduction of anthracyclines to adjuvant chemotherapy has increased survival rates among breast cancer patients. Cyclophosphamide, epirubicin and 5-fluorouracil (CEF) combination therapy is now one of the preferred regimens for treating node-positive breast cancer due to better survival with less toxicity involved. Despite the increasing use of CEF, its potential in causing adverse skeletal effects remains unclear. Using a mature female rat model mimicking the clinical setting, this study examined the effects of CEF treatment on bone and bone marrow in long bones. Following six cycles of CEF treatment (weekly intravenous injections of cyclophosphamide at 10 mg/kg, epirubicin at 2.5 mg/kg and 5-flurouracil at 10 mg/kg), a significant reduction in trabecular bone volume was observed at the metaphysis, which was associated with a reduced serum level of bone formation marker alkaline phosphatase (ALP), increased trends of osteoclast density and osteoclast area at the metaphysis, as well as an increased size of osteoclasts being formed from the bone marrow cells ex vivo. Moreover, a severe reduction of bone marrow cellularity was observed following CEF treatment, which was accompanied by an increase in marrow adipose tissue volume. This increase in marrow adiposity was associated with an expansion in adipocyte size but not in marrow adipocyte density. Overall, this study indicates that six cycles of CEF chemotherapy may induce some bone loss and severe bone marrow damage. Mechanisms for CEF-induced bone/bone marrow pathologies and potential preventive strategies warrant further investigation.

  9. Chemoneuroendocrine therapy of metastatic breast cancer with persistent thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II study.

    PubMed

    Lissoni, P; Tancini, G; Paolorossi, F; Mandalà, M; Ardizzoia, A; Malugani, F; Giani, L; Barni, S

    1999-04-01

    Thrombocytopenia is a frequent complication of cancer and constitutes an absolute contraindication for chemotherapy. Recent studies have demonstrated that platelet generation may be influenced by both cytokines and neurohormones. In particular, the pineal indole melatonin has been proven to enhance platelet number in patients with thrombocytopenia due to different reasons. On this basis, we have evaluated the effects of a concomitant administration of melatonin in thrombocytopenic cancer patients undergoing chemotherapy. The study was performed in 14 metastatic breast cancer women treated by weekly epirubicin. Each cycle consisted of epirubicin at 25 mg/m2 i.v. at weekly intervals. Melatonin was given orally at 20 mg/day in the evening every day, starting 7 days prior to chemotherapy. Patients were considered as evaluable when they received at least four cycles of chemotherapy. Evaluable patients were 12/14. The induction phase with melatonin induced a normalization of platelet number in 9/12 evaluable patients, and no further platelet decline occurred in chemotherapy. Objective tumor regression was achieved in 5/12 (41%) patients. This preliminary study would suggest that melatonin may be effective in the treatment of cancer-related thrombocytopenia and to prevent chemotherapy-induced platelet decline. Until now, melatonin therapy of cancer has been generally considered as an alternative treatment to chemotherapy. In contrast, this study would suggest that melatonin may contribute to the realization of chemotherapy in metastatic cancer patients unable to tolerate the chemotherapeutic approach because of persistent thrombocytopenia.

  10. 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

  11. 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.

  12. Effect of combined treatment with the epirubicin-incorporating micelles (NC-6300) and 1,2-diaminocyclohexane platinum (II)-incorporating micelles (NC-4016) on a human gastric cancer model.

    PubMed

    Yamamoto, Yoshiyuki; Hyodo, Ichinosuke; Takigahira, Misato; Koga, Yoshikatsu; Yasunaga, Masahiro; Harada, Mitsunori; Hayashi, Tatsuyuki; Kato, Yasuki; Matsumura, Yasuhiro

    2014-07-01

    Anticancer agent-incorporating polymeric micelles accumulate effectively in tumors via the enhanced permeability and retention effect to exert potent antitumor effects. However, combined use of such micelles has not been elucidated. We compared the effect of combining the epirubicin-incorporating micelle NC-6300 and 1,2-diaminocyclohexane platinum (II) (oxaliplatin parent complex)-incorporating micelle NC-4016 (NCs) with that of epirubicin and oxaliplatin (E/O) in 44As3Luc cells using the combination index method. The in vivo antitumor activities of NCs and E/O were evaluated in mice bearing 44As3Luc xenografts. Pharmacokinetic analysis was performed by high-performance liquid chromatography and mass spectrometry. Cardiotoxicity of NC-6300 and epirubicin was assessed by echocardiography. Neurotoxicity of NC-4016 and oxaliplatin was evaluated by examining the paw withdrawal response to noxious mechanical stimuli. NCs showed a highly synergistic activity equivalent to E/O. In vivo, NCs exhibited higher antitumor activity in the subcutaneous tumor model and longer overall survival in the orthotopic tumor model than E/O (p < 0.001, p = 0.015, respectively). The intratumor concentrations of epirubicin and platinum were significantly higher following NCs than following E/O administration. Moreover, the micelles showed lower cardiotoxicity and neurotoxicity than the corresponding conventional drugs. The combined use of the micelles was associated with remarkable efficacy and favorable toxicities in the human gastric cancer model, and warrants the conduct of clinical trials. © 2013 UICC.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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)

  1. 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.

  2. 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

  3. 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

  4. 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%.

  5. Neoadjuvant Sequential Docetaxel Followed by High‐Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial

    PubMed Central

    Pizzuti, Laura; Barba, Maddalena; Giannarelli, Diana; Sergi, Domenico; Botti, Claudio; Marchetti, Paolo; Anzà, Michele; Maugeri‐Saccà, Marcello; Natoli, Clara; Di Filippo, Simona; Catenaro, Teresa; Tomao, Federica; Amodio, Antonella; Carpano, Silvia; Perracchio, Letizia; Mottolese, Marcella; Di Lauro, Luigi; Sanguineti, Giuseppe; Di Benedetto, Anna; Giordano, Antonio

    2016-01-01

    To report the results of the DECT trial, a phase II study of locally advanced or operable HER2‐positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA‐IIIB HER2‐positive BC, 18–75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3‐weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide, 600 mg/m2, plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8–78). Four‐year recurrence‐free survival was 74.7% (95%CI, 58.2–91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541–2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:27187274

  6. Utility of epirubicin-incorporating micelles tagged with anti-tissue factor antibody clone with no anticoagulant effect.

    PubMed

    Sugaya, Akinori; Hyodo, Ichinosuke; Koga, Yoshikatsu; Yamamoto, Yoshiyuki; Takashima, Hiroki; Sato, Ryuta; Tsumura, Ryo; Furuya, Fumiaki; Yasunaga, Masahiro; Harada, Mitsunori; Tanaka, Ryosuke; Matsumura, Yasuhiro

    2016-03-01

    Tissue factor (TF), an initiator of the extrinsic blood coagulation cascade, is overexpressed in different types of cancer. Tissue factor overexpression is also known as a poor prognostic factor in pancreatic cancer. We recently developed anti-TF antibody (clone1849)-conjugated epirubicin-incorporating micelles (NC-6300), and reported that this anti-TF1849-NC-6300 showed enhanced antitumor activity against TF-high expressed human pancreatic cancer cells, when compared with NC-6300 alone. However, clone 1849 antibody inhibited TF-associated blood coagulation activity. We studied another anti-TF antibody, clone 1859, which had no effect on blood coagulation and prepared anti-TF1859-NC-6300. In addition, to determine the optimum size of the antibody fragment to conjugate with NC-6300, three forms of the 1859 antibody (whole IgG, F[ab']2 , and Fab') were conjugated to NC-6300. The antitumor effect of each anti-TF1859-NC-6300 was studied in vitro and in vivo, using two human pancreatic cancer cell lines, BxPC3 with high-expressed TF, and SUIT2 with low levels of TF. In vitro, all forms of anti-TF1859-NC-6300 showed higher cytocidal effects than NC-6300 in BxPC3, whereas this enhanced effect was not observed in SUIT2. Likewise, all forms of anti-TF1859-NC-6300 significantly suppressed tumor growth when compared to NC-6300 in the BxPC3, but not in the SUIT2, xenograft model. Among the three forms of conjugates, anti-TF1859-IgG-NC-6300 had a higher antitumor tendency in TF-high expressed cells. Thus, we have confirmed an enhanced antitumor effect of anti-TF1859-NC-6300 in a TF-high expressing tumor; anti-TF1859-IgG-NC-6300 could be used to simplify the manufacturing process of the antibody-micelle conjugation for future clinical studies. © 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Dynamic contrast-enhanced MR imaging in a phase Ⅱ study on neoadjuvant chemotherapy combining Rh-endostatin with docetaxel and epirubicin for locally advanced breast cancer.

    PubMed

    Jia, Qianxin; Xu, Junqing; Jiang, Weifeng; Zheng, Minwen; Wei, Mengqi; Chen, Jianghao; Wang, Ling; Huan, Yi

    2013-01-01

    Anti-angiogenesis is a promising therapeutic strategy for locally advanced breast cancer. We performed this phase II trial to evaluate the anti-angiogenesis and anti-tumor effect of rh-endostatin combined with docetaxel and epirubicin in patients with locally advanced breast cancer by dynamic contrast-enhanced magnetic resonance imaging in 70 previously untreated locally advanced breast cancer patients. The study population was randomly assigned to neoadjuvant chemotherapy with docetaxel and epirubicin (neoadjuvant chemotherapy group) or neoadjuvant chemotherapy combining rh-endostatin with docetaxel and epirubicin (neoadjuvant chemotherapy+rh-endostatin group). The anti-angiogenic and anti-tumor effects of both regimens were evaluated by serial dynamic contrast-enhanced magnetic resonance imaging and microvessel density measurements after final surgery. The results suggested a higher clinical objective response (90.9% vs. 67.7%, P = 0.021) and greater reductions in tumor size (67.2% vs. 55.9%, P = 0.000), Ki-67 proliferation index (32.79% vs. 12.47%, P = 0.000), tumor signal enhanced ratio (64% vs. 48%, P = 0.018), and K(trans) (67% vs. 39%, P = 0.026) in neoadjuvant chemotherapy+rh-endostatin group than those in neoadjuvant chemotherapy group. In addition, the microvessel density value in the neoadjuvant chemotherapy+rh-endostatin group was significantly lower than in the neoadjuvant chemotherapy group (18.67 ± 6.53 vs. 36.05 ± 9.64, P = 0.000). Moreover, the microvessel density value was significantly correlated with K(trans) after neoadjuvant chemotherapy+rh-endostatin treatment (r=0.88, P = 0.00). The neoadjuvant chemotherapy+rh-endostatin treatment significantly repressed angiogenesis in locally advanced breast cancer and synergistically enhanced the anti-tumor effect of neoadjuvant chemotherapy. Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and K(trans), could provide non-invasive evaluation for

  13. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial

    PubMed Central

    Waddell, Tom; Chau, Ian; Cunningham, David; Gonzalez, David; Okines, Alicia Frances Clare; Wotherspoon, Andrew; Saffery, Claire; Middleton, Gary; Wadsley, Jonathan; Ferry, David; Mansoor, Wasat; Crosby, Tom; Coxon, Fareeda; Smith, David; Waters, Justin; Iveson, Timothy; Falk, Stephen; Slater, Sarah; Peckitt, Clare; Barbachano, Yolanda

    2013-01-01

    Summary Background EGFR overexpression occurs in 27–55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. Methods In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m2 and oxaliplatin 130 mg/m2 on day 1 and capecitabine 1250 mg/m2 per day on days 1–21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m2 and oxaliplatin 100 mg/m2 on day 1, capecitabine 1000 mg/m2 per day on days 1–21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. Findings Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11·3 months (95% CI 9·6–13·0) compared with 8·8 months (7·7–9·8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1·37, 95% CI 1·07–1·76; p=0·013). mEOC+P was associated with increased incidence of grade 3–4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two

  14. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial.

    PubMed

    Waddell, Tom; Chau, Ian; Cunningham, David; Gonzalez, David; Okines, Alicia Frances Clare; Frances, Alicia; Okines, Clare; Wotherspoon, Andrew; Saffery, Claire; Middleton, Gary; Wadsley, Jonathan; Ferry, David; Mansoor, Wasat; Crosby, Tom; Coxon, Fareeda; Smith, David; Waters, Justin; Iveson, Timothy; Falk, Stephen; Slater, Sarah; Peckitt, Clare; Barbachano, Yolanda

    2013-05-01

    EGFR overexpression occurs in 27-55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1250 mg/m(2) per day on days 1-21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m(2) and oxaliplatin 100 mg/m(2) on day 1, capecitabine 1000 mg/m(2) per day on days 1-21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11.3 months (95% CI 9.6-13.0) compared with 8.8 months (7.7-9.8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1.37, 95% CI 1.07-1.76; p=0.013). mEOC+P was associated with increased incidence of grade 3-4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and

  15. Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer: evaluation of efficacy and safety.

    PubMed

    Shimada, Hiroko; Ueda, Shigeto; Saeki, Toshiaki; Shigekawa, Takashi; Takeuchi, Hideki; Hirokawa, Eiko; Sugitani, Ikuko; Sugiyama, Michiko; Takahashi, Takao; Matsuura, Kazuo; Yamane, Tomohiko; Kuji, Ichiei; Hasebe, Takahiro; Osaki, Akihiko

    2015-07-01

    Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity. The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel. Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w), followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated. In addition, the clinical response, breast-conserving rate and safety of this treatment were monitored. Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy, pathological complete response and near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%) patients who had surgery, respectively. The overall objective response rate was 71.7% after completion of chemotherapy. Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete metabolic response and partial metabolic response after 2-3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%) patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events. Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance, but conferred a low rate of pathological complete response. Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in

  16. Phase I study of 3-weekly combination chemotherapy using epirubicin, oxaliplatin, and S-1 (EOS) in patients with previously untreated advanced gastric cancer.

    PubMed

    Sym, Sun Jin; Hong, Junsik; Jung, Minkyu; Park, Jinny; Cho, Eun Kyung; Lee, Woon Ki; Chung, Min; Kim, Hyung-Sik; Lee, Jae Hoon; Shin, Dong Bok

    2012-08-01

    This study was performed to determine the recommended dose (RD) and dose-limiting toxicity (DLT) associated with epirubicin, oxaliplatin, and S-1 (EOS) combination therapy in patients with previously untreated advanced gastric cancer (AGC). Previously untreated patients with histologically proven metastatic AGC, with an ECOG performance status of 0-2, were enrolled in this study. A fixed dose of epirubicin (50 mg/m(2)) and oxaliplatin (130 mg/m(2)) was intravenously administered on day 1 of treatment, followed by oral S-1 administration twice daily on days 1-14. The S-1 dose was escalated according to the following schedule: level I, 35 mg/m(2); level II, 40 mg/m(2); level III, 45 mg/m(2); Level IV, 50 mg/m(2). Each cycle was repeated every 21 days. DLTs were evaluated during the first two cycles of treatment. Nineteen patients with a median age of 53 years (range, 40-71 years) were enrolled in this study. One case of DLT (grade 4 neutropenia lasting more than 5 days) developed from among the six dose level II patients, while 2 DLTs (grade 3 diarrhea and nausea) were observed among the 4 dose level III patients. Based on these results, dose level II was determined as the RD. Of the 13 patients with measurable lesions, eight achieved partial response, three showed stable disease, and the objective response rate was 61.5 % (95 % confidence interval (CI), 13.3-66.6 %). The median progression-free survival and overall survival of all patients was 6.8 months (95 % CI, 1.4-9.5 months) and 13.3 months (95 % CI, 1.9-24.6 months), respectively. The RD of the EOS regimen in patients with previously untreated AGC was 50 mg/m(2) of epirubicin and 130 mg/m(2) of oxaliplatin on day 1, with administration of 40 mg/m(2) of S-1 twice a day on days 1-14 for each 21-day cycle. The EOS regimen described produced promising results.

  17. 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.

  18. 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…

  19. 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…

  20. 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.

  1. 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.

  2. 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…

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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 ...

  11. 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 ...

  12. Synthesis and characterization of non-toxic and thermo-sensitive poly(N-isopropylacrylamide)-grafted cashew gum nanoparticles as a potential epirubicin delivery matrix.

    PubMed

    Abreu, Clara M W S; Paula, Haroldo C B; Seabra, Vitor; Feitosa, Judith P A; Sarmento, Bruno; de Paula, Regina C M

    2016-12-10

    Cashew gum (CG) was grafted with N-isopropylacrylamide (NIPA) by radical polymerization to originate a stimuli-sensitive copolymer for drug delivery purposes. NMR and IR spectroscopy confirmed the insertion of NIPA onto the cashew gum chains. The graft copolymer (CG:NIPA) demonstrated thermal responsiveness. The critical aggregation concentration of the copolymers at 25°C was higher than at 50°C. At temperatures lower than the LCST, the nanoparticle size ranged from 12 to 21nm, depending on the CG:NIPA ratio, but above the LCST the particles aggregated, increasing the particle size. Regarding the potential for future oral application, the nanoparticles showed no cytotoxic activity against the Caco-2 and HT29-MTX intestine cell lines. Epirubicin was encapsulated into nanoparticles of CG-NIPA (1:1), resulting in a 64% association efficiency and 22% loading capacity. Thus, the CG:NIPA graft copolymer demonstrates good potential for used in controlled drug delivery systems.

  13. 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 - ...

  14. Coupled-column liquid chromatographic analysis of epirubicin and metabolites in biological material and its application to optimization of liver cancer therapy.

    PubMed

    Rudolphi, A; Vielhauer, S; Boos, K S; Seidel, D; Bäthge, I M; Berger, H

    1995-04-01

    A specific, sensitive and fully automated coupled-column LC method for the determination of the anthracycline cytostatic epirubicin and four metabolites in the biological materials human plasma, liver homogenate and liver tumour homogenate has been developed. System-integrated sample processing was achieved using a new restricted access silica precolumn packing. This porous Alkyl-Diol Silica (ADS) was specially designed for the direct and repetitive injection of proteinaceous samples. It consists of a hydrophilic and electroneutral external particle surface (glyceryl-residues) and a hydrophobic reversed-phase internal surface (butyryl-, octanoyl- or octadecyl-residues). These bimodal chromatographic properties allow retention of low molecular analytes by classical RP-chromatography exclusively at the lipophilic pore surface. Macromolecular constituents of the sample matrix (e.g. proteins) are size-excluded by 5 nm pores and quantitatively eliminated in the interstitial void volume. On-line analysis was performed by coupling a C4-Alkyl-Diol precolumn (20 x 4 mm i.d., particle size 25 microns) and LiChrospher RP Select B analytical column (250 x 4 mm i.d., particle size 5 microns) via an electrically driven six-port valve. Separation of the parent compound and its metabolites was achieved with a mobile phase consisting of water (0.1% triethylamine, v/v, pH 2.0 adjusted with trichloroacetic acid)-acetonitrile (70:30, v/v) at a flow rate of 1 ml min-1. The analytes were detected using their natural fluorescence (excitation 445 nm, emission 560 nm). The method described is used for the determination of pharmacokinetics of epirubicin and its metabolites in order to evaluate and optimize treatment regimen of liver cancer chemoembolization therapy.

  15. Quality of life in women with metastatic breast cancer during 9 months after randomization in the TEX trial (epirubicin and paclitaxel w/o capecitabine).

    PubMed

    Svensson, Helene; Einbeigi, Zakaria; Johansson, Hemming; Hatschek, Thomas; Brandberg, Yvonne

    2010-10-01

    The aim of this study was to compare the effects on health-related quality of life (HRQOL) of two treatment regimens in the TEX trial during 9 month from random assignment, with emphasis on the 2- and 9-months assessments. A total of 287 patients were randomized to treatment in 3-week cycles with either epirubicin plus paclitaxel (ET, 143 patients), or epirubicin, paclitaxel and capecitabine (TEX, 144 patients). HRQOL was assessed by the EORTC-QLQ C30 and EORTC QLQ-BR23 questionnaires at five points during 9 months. A total of 252 (88%) completed questionnaires before randomization. Response rate for the following assessments was >75%. There were no statistically significant differences between the TEX group and the ET group on any of the subscales 2 months after randomization. Small clinical differences (5-10 points) in favor of the ET group were found for global quality of life, role functioning, social functioning, and insomnia. At the 9-months assessment, the TEX group scored statistically significantly higher on global quality of life and physical functioning. Small clinically significant differences were found for global quality of life, physical functioning, role functioning, emotional functioning, dyspnoea, and insomnia, all in favour of the TEX group. At the 2-months assessment, when side-effects of chemotherapy were present, patients in the TEX group appeared to fare a bit worse than those receiving ET. However, after 9 months, when the patients had adapted to treatment, the TEX group seemed to have a slightly better quality of life.

  16. A randomised phase II study of combination chemotherapy with epirubicin, cisplatin and capecitabine (ECX) or cisplatin and capecitabine (CX) in advanced gastric cancer.

    PubMed

    Yun, Jina; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki

    2010-03-01

    Both cisplatin/capecitabine (CX) and epirubicin plus CX (ECX) have clearly demonstrated efficacy against advanced gastric cancer (AGC). Chemotherapy-naïve patients with histologically confirmed, measurable AGC were randomised to receive CX (cisplatin 75mg/m(2) iv on day 1 and capecitabine 1000mg/m(2) bid po on days 1-14) or ECX (epirubicin 50mg/m(2) plus CX) every 3weeks. The primary endpoint was progression-free survival (PFS). Of the 91 registered patients, 45 patients were treated with CX and 44 with ECX. A total of 241 CX (median, 6; range, 1-12) and 201 ECX (median, 5; range, 1-11) cycles were delivered. Treatment duration was similar for both arms (4.4 for CX versus 4.2months for ECX). There was no relevant difference in the occurrence of overall grade 3 or 4 toxicities between the CX and ECX arms (80% versus 78%, respectively; P=0.516). However, none in the CX and 12% in the ECX arm discontinued treatment because of toxicity. There were no significant differences in therapeutic efficacy between CX and ECX with respect to the response rate (38% versus 37%, respectively) and PFS (6.4 versus 6.5months). Both CX and ECX appear to be active as first-line chemotherapy for AGC, and the safety profiles are acceptable. Given the comparable efficacy results, CX could be a reasonable standard chemotherapy for untreated AGC patients. Copyright 2009 Elsevier Ltd. All rights reserved.

  17. Surface decorated nanoparticles as surrogate carriers for improved transport and absorption of epirubicin across the gastrointestinal tract: Pharmacokinetic and pharmacodynamic investigations.

    PubMed

    Tariq, Mohammad; Alam, Md Aftab; Singh, Anu T; Panda, Amulya K; Talegaonkar, Sushama

    2016-03-30

    Epirubicin (EPI) is a P-gp substrate antracycline analogue which elicits poor oral bioavailability. In the present work, EPI loaded poly-lactide-co-glycolic acid nanoparticles (PLGA-NPs) were prepared by double emulsion approach and superficially decorated with polyethylene glycol (EPI-PNPs) and mannosamine (EPI-MNPs). Average hydrodynamic particle size of EPI-PNPs and EPI-MNPs was found 248.63 ± 12.36 and 254.23 ± 15.16 nm, respectively. Cytotoxicity studies were performed against human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of EPI-PNPs and EPI-MNPs over free epirubicin solution (EPI-S). Further, confocal laser scanning microscopy (CLSM) and flow cytometric analysis (FACS) demonstrated enhanced drug uptake through EPI-PNPs and EPI-MNPs and elucidated dominance of caveolae mediated endocytosis for NPs uptake. Cellular transport conducted on human colon adenocarcinoma cell line (Caco-2) showed 2.45 and 3.17 folds higher permeability of EPI through EPI-PNPs and EPI-MNPs when compared with EPI-S (p<0.001) while permeability of EPI was found 5.23 and 5.67 folds higher across rat ileum, respectively. Furthermore, pharmacokinetic studies demonstrated 4.7 and 5.57 folds higher oral bioavailability through EPI-PNPs and EPI-MNPs when compared with EPI-S. In addition, both, EPI-PNPs and EMNPs showed tumor suppression comparable to indicated route (i.v. injection). EPI-MNPs showed 1.18 folds higher bioavailability and better tumor suppression than EPI-PNPs.

  18. Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study.

    PubMed

    Sayal, Karen; Gounaris, Ioannis; Basu, Bristi; Freeman, Sue; Moyle, Penny; Hosking, Karen; Iddawela, Mahesh; Jimenez-Linan, Mercedes; Abraham, Jean; Brenton, James; Hatcher, Helen; Earl, Helena; Parkinson, Christine

    2015-07-01

    Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome "resistance" in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. [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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. [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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. [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.

  16. 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 ...

  17. [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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. A randomised pilot Phase II study of doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC) given 2 weekly with pegfilgrastim (accelerated) vs 3 weekly (standard) for women with early breast cancer

    PubMed Central

    Jones, R L; Walsh, G; Ashley, S; Chua, S; Agarwal, R; O'Brien, M; Johnston, S; Smith, I E

    2009-01-01

    Accelerated (dose-dense) chemotherapy, in which the frequency of administration is increased without changing total dose or duration, may increase the efficacy of cancer chemotherapy. We performed a randomised Phase II study to assess the safety and relative toxicity of AC (doxorubicin; cyclophosphamide) vs E(epirubicin)C given by conventional or accelerated schedules as neoadjuvant or adjuvant chemotherapy for early breast cancer. Furthermore, the relative toxicity of doxorubicin and epirubicin remains uncertain. Patients were randomised to one of four arms; four courses of standard 3 weekly cyclophosphamide 600 mg m−2 in combination with doxorubicin 60 mg m−2 (AC) vs epirubicin 90 mg m−2 (EC) 3 weekly vs the same regimens administered every 2 weeks with pegfilgrastim (G-CSF). A total of 126 patients were treated, 42 with standard AC, 42 with accelerated AC, 19 with standard EC and 23 with accelerated EC. Significantly more grade 3/4 day one neutropenia was seen with standard (6/61, 10%) compared to accelerated (0/65,) regimens (P=0.01). A trend towards more neutropenic sepsis was seen in the combined standard and accelerated AC arms (12/84, 14%) compared to the combined EC arms (1/42, 2%), P=0.06. Falls in left ventricular ejection fraction were not increased with accelerated treatment. Accelerated AC and EC with pegfilgrastim are safe and feasible regimens in the treatment of early breast cancer with less neutropenia than conventional 3 weekly schedules. PMID:19165198

  4. Interim prostacyclin therapy for an isolated disconnected pulmonary artery: a case report.

    PubMed

    Grech, Victor; Grixti, Cynthia

    2010-06-02

    Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation.

  5. Retrograde arterial leg blood flow during tilt-back from a head-up posture: importance of capacitive flows when arterial pressure changes.

    PubMed

    Sheriff, Don D; Nådland, Inger Helene; Toska, Karin

    2010-03-01

    The windkessel function of the arterial system converts the intermittent action of the heart into more continuous microcirculatory blood flow during diastole via the return of elastic energy stored in the walls of the arteries during systole. Might the same phenomenon occur regionally within the arterial system during tilting owing to regional differences in local arterial pressure imposed by gravity? We sought to test the hypothesis that during tilt-back from a head-up posture, the return of stored elastic energy in leg arteries would work to slow, or perhaps transiently reverse, the flow of blood in the femoral artery. Femoral artery blood flow and arterial pressure were recorded during tilt back from a 30 degrees head-up posture to supine (approximately 0.5 G) in young, healthy subjects (n = 7 males and 3 females) before and during clonidine infusion. During control (no drug) conditions femoral artery blood flow ceased for an entire heart beat during tilt-back. During clonidine infusion femoral artery blood flow reversed for at least one entire heart beat during tilt-back, i.e., blood flow in the retrograde direction in the femoral artery from the leg into the abdomen. Thus substantial capacitive effects of tilting on leg blood flow occur in humans during mild changes in posture.

  6. Carotid Artery Screening

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Carotid Artery Screening What is carotid artery screening? Who should ... information about carotid artery screening? What is carotid artery screening? Screening examinations are tests performed to find ...

  7. Coronary Artery Bypass Grafting

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Coronary Artery Bypass Grafting? Coronary artery bypass grafting (CABG) is ... bypass multiple coronary arteries during one surgery. Coronary Artery Bypass Grafting Figure A shows the location of ...

  8. Relationship between gated myocardial perfusion SPECT findings and hemodynamic, electrocardiographic, and heart rate changes after Dipyridamole infusion.

    PubMed

    Gholoobi, Arash; Ayati, Narjess; Baghyari, Alireza; Mouhebati, Mohsen; Atar, Baharak; Dabbagh Kakhki, Vahid Reza

    2017-02-01

    After dipyridamole infusion, electrocardiographic (ECG), blood pressure and heart rate (HR) changes were seen. We tried to investigate whether there is a relationship between hemodynamic, ECG and HR changes after dipyridamole infusion and gated myocardial perfusion SPECT findings. We studied 206 consecutive patients which underwent a 2-day protocol Dipyridamole Stress/Rest Tc99m-Sestamibi gated myocardial perfusion SPECT. Systolic blood pressure (SBP), diastolic blood pressure (DBP), HR and ECG were recorded. HR was mildly increased while SBP and DBP were mildly decreased after Dipyridamole infusion. There was only statistically significant difference between ECG changes as well as transient ischemic dilation (TID) ratio between normal scans and scans with ischemia (P = 0.02 and P = 0.01 respectively). There was correlation between these variables and summed stress score (SSS) and summed difference score (SDS). Patients with ischemia in their scans, 44.3% had ST depression after Dipyridamole infusion. Also ST depression most frequently was seen in patients with left anterior descending artery disease. From patients with abnormal scan + ST depression after Dipyridamole infusion (33 patient), 27 patient (81.81%) had ischemia. There was an association between TID ratio as well as ECG changes after Dipyridamole infusion and SSS, SDS and coronary artery territory abnormality. Difference between calculated left ventricular ejection fraction using stress and rest images had significant correlation with SSS and SDS. ST depression after Dipyridamole infusion and TID ratio had association with ischemia, SSS and SDS. So in equivocal Gated SPECT findings, they could be very useful for interpretation.

  9. A remote drip infusion monitoring system employing Bluetooth.

    PubMed

    Amano, Hikaru; Ogawa, Hidekuni; Maki, Hiromichi; Tsukamoto, Sosuke; Yonezawa, Yoshiharu; Caldwell, W Morton

    2012-01-01

    We have developed a remote drip infusion monitoring system for use in hospitals. The system consists of several infusion monitoring devices and a central monitor. The infusion monitoring device employing a Bluetooth module can detect the drip infusion rate and an empty infusion solution bag, and then these data are sent to the central monitor placed at the nurses' station via the Bluetooth. The central monitor receives the data from several infusion monitoring devices and then displays graphically them. Therefore, the developed system can monitor intensively the drip infusion situation of the several patients at the nurses' station.

  10. Effects of calcium infusion on secretion and motor activity of totally isolated canine stomach perfused with homologous blood.

    PubMed

    Kowalewski, K; Kolodej, A

    1976-01-01

    Isolated, ex vivo perfused, canine stomachs were used for this study. Gastric secretion, myoelectrical activity and mechanical activity were recorded during stimulation of gastric function with pentagastrin or histamine alone or combined with calcium gluconate. Secretagogues and calcium were infused into the gastric arterial circulation. Hypercalcemia induced significant inhibition of pentagastrin, stimulated gastric secretion, but did not affect the secretion stimulated by histamine. Hypercalcemia also induced an increase of frequency of cycles of electrical control activity and a decrease of mechanical activity of the gastric antrum. The effect of hypercalcemia on gastric motor function was similar in the nonstimulated stomach and during the infusion of secretagogues used in this experiment.

  11. Arterial embolism

    MedlinePlus

    ... for embolization (especially to the brain) is mitral stenosis . Endocarditis (infection of the inside of the heart) can also cause arterial emboli. A common source for an embolus is from areas of hardening (atherosclerosis) in the aorta and other large blood vessels. These clots can ...

  12. Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion

    PubMed Central

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

    2007-01-01

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

  13. Initial Observations of the Effects of Calcium Chloride Infusions in Pediatric Patients with Low Cardiac Output.

    PubMed

    Averin, Konstantin; Villa, Chet; Krawczeski, Catherine D; Pratt, Jesse; King, Eileen; Jefferies, John L; Nelson, David P; Cooper, David S; Ryan, Thomas D; Sawyer, Jaclyn; Towbin, Jeffrey A; Lorts, Angela

    2016-03-01

    Myocardial contractility and relaxation are highly dependent on calcium homeostasis. Immature myocardium, as in pediatric patients, is thought to be more dependent on extracellular calcium for optimal function. For this reason, intravenous calcium chloride infusions may improve myocardial function in the pediatric patient. The objectives of this study were to report the hemodynamic changes seen after administration of continuous calcium chloride to critically ill children. We retrospectively identified pediatric patients (newborn to 17 years old) with hemodynamic instability admitted to the cardiac ICU between May 2011 and May 2012 who received a continuous infusion of calcium chloride. The primary outcome was improvement in cardiac output, assessed by arterial-mixed venous oxygen saturation (A-V) difference. Sixty-eight patients, mean age 0.87 ± 2.67 years, received a total of 116 calcium infusions. Calcium chloride infusions resulted in significant improvements in primary and secondary measures of cardiac output at 2 and 6 h. Six hours after calcium initiation, A-V oxygen saturation difference decreased by 7.4 % (32.6 ± 2.1 to 25.2 ± 2.0 %, p < 0.001), rSO2 increased by 5.5 % (63.1 vs 68.6 %, p < 0.001), and serum lactate decreased by 0.9 mmol/l (3.3 vs 2.4 mmol/l, p < 0.001) with no change in HR (149.1 vs 145.6 bpm p = 0.07). Urine output increased 0.66 ml/kg/h in the 8-h period after calcium initiation when compared to pre-initiation (p = 0.003). Neonates had the strongest evidence of effectiveness with other age groups trending toward significance. Calcium chloride infusions improve markers of cardiac output in a heterogenous group of pediatric patients in a cardiac ICU. Neonates appear to derive the most benefit from utilization of these infusions.

  14. Assessment of macro- and micro-oxygenation parameters during fractional fluid infusion: A pilot study.

    PubMed

    Fischer, Marc-Olivier; Bonnet, Vincent; Lorne, Emmanuel; Lefrant, Jean-Yves; Rebet, Olivier; Courteille, Benoît; Lemétayer, Charlotte; Parienti, Jean-Jacques; Gérard, Jean-Louis; Fellahi, Jean-Luc; Hanouz, Jean-Luc

    2017-08-01

    The main goal of this study was to assess whether maximal fluid infusion improves both oxygen delivery (DO2) and micro-circulatory parameters during hemodilution. The secondary objective was to assess the ability of baseline micro-circulatory parameters to predict oxygen consumption (VO2) response following fluid infusion. In a postoperative cardiac ICU, patients received repeated fluid infusion until stroke volume (SV) was maximized. Before and after each fluid expansion, macro- (DO2, VO2) and micro-circulatory oxygenation parameters were recorded [central venous oxygen saturation (ScVO2), blood lactate, difference in veno-arterial carbon dioxide tension (P(v-a)CO2), somatic and cerebral oxygen saturation (rSO2)]. Patients were classified as VO2-Responders or VO2-Non-Responders according to an increase in VO2 above or below 15%, respectively. After maximal fluid infusion, all patients showed improved macro- and micro-circulatory oxygenation parameters, but VO2-Responders had lower values (especially for ScVO2 and cerebral rSO2). Only baseline ScVO2 and cerebral rSO2 were useful to predict the VO2 response to maximal fluid infusion (ROCAUC 0.80 (95% CI: 0.54-0.95, P=0.012) and 0.83 (95% CI: 0.57-0.96, P=0.001). Maximal fluid infusion improves macro- and micro-circulatory oxygenation parameters. For VO2-Responders, only ScVO2 and cerebral rSO2 could serve as markers of tissue hypoxia. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Modulation of plasma adrenomedullin by epinephrine infusion during head up tilt.

    PubMed

    Roessler, Andreas; Goswami, Nandu; Haditsch, Bernd; Hinghofer-Szalkay, Helmut

    2011-03-01

    We investigated whether head up tilt (HUT) with and without simultaneous epinephrine infusion modulate plasma adrenomedullin. We studied eight healthy male volunteers, using two 5 min 70° HUT trials: control (saline infusion) and intervention (epinephrine infusion, titrated to a dose which increased supine systolic pressure by 20% above resting values). Protocols were randomized and separated by 2 weeks. Cardiac function and systolic time intervals, recorded using a phonocardiograph microphone, included left ventricular ejection time (LVET), pre-ejection period (PEP), PEP/LVET and electromechanical systole (QS2). Compared to saline infusion, epinephrine increased supine adrenomedullin (3.2 ± 0.8 pmol/l, i.e., mean ± SEM, respectively), heart rate (HR) (+11.3 ± 2.6 bpm), systolic pressure (+18.4 ± 2.6 mmHg) but decreased supine LVET, LVET corrected for HR (LVETi) and QS2-time (all p = 0.004). Despite similar HUT induced thoracic fluid shifts, reflected by similar thoracic impedance changes, HUT-induced adrenomedullin increases were minimal in epinephrine-supplemented men in comparison to controls (+8% vs. 42%). During HUT, epinephrine infusion decreased only the LVET (p = 0.039). Our findings confirm that short-term HUT increases plasma adrenomedullin. They further suggest that with increased supine epinephrine levels (epinephrine infusion clamping systolic arterial pressure at 120% control level), supine cardiac performance rises to a level similar to that during HUT, while adrenomedullin is still elevated with HUT. This might be in accordance with a 'dampening' role of adrenomedullin during catecholaminergic cardiovascular stimulation. As epinephrine is used as a drug to treat cardiac arrest and ventricular arrhythmias, our results may have important clinical/emergency resuscitation applications.

  16. Real-time myocardial contrast echocardiography in rat: infusion versus bolus administration.

    PubMed

    Su, Hai-Li; Qian, Yun-Qiu; Wei, Zhang-Rui; He, Jian-Guo; Li, Guo-Quan; Zhang, Jun; Zhou, Xiao-Dong; Jing, Wang

    2009-05-01

    To compare the feasibility of real-time myocardial contrast echocardiography (MCE) in rats with infusion and bolus administration of a second-generation ultrasound contrast agent BR1. B-mode real-time MCE was performed in 12 Sprague Dawley rats following the BR1 infusion or bolus injection. The myocardium signal intensity (SI) was plotted against time and was fitted to exponential functions. The plateau SI (A) and rate of SI increase (beta) for the infusion study and peak signal intensity (PSI) for the bolus study were obtained. (99m)Tc-Sestamibi and Evans blue were used to assess myocardial blood perfusion and to calculate the myocardium perfusion defect area ex vivo. High-quality real-time MCE images were successfully obtained using each method. At baseline, all LV segments showed even contrast distribution. Following left anterior descending coronary artery (LAD) ligation, significant perfusion defect was observed in LAD beds with a significantly decreased A* beta and PSI values compared with LCx beds (Infusion: A*beta (LAD): 5.42 +/- 1.57 dB, A*beta (LCx): 46.52 +/- 5.32 dB, p < 0.05; Bolus: PSI (LAD): 2.11 +/- 0.67 dB, PSI (LCx): 20.68 +/- 0.72 dB, p < 0.05), which was consistent with (99m)Tc-Sestamibi distribution findings. Myocardial perfusion defect areas, assessed by both methods, showed no differences and showed good correlation with Evans blue staining. ED frames were more favorable for imaging analysis. Both infusion and bolus administration of the contrast agent combined with real-time MCE technique can provide a reliable and noninvasive approach for myocardial perfusion assessment in rats and the infusion method was more suitable for quantitative analysis of myocardial blood flow.

  17. Myocardial imaging using thallium 201 scintigraphy after dipyridamole infusion: A case history

    SciTech Connect

    Niemeyer, M.G.; van der Wall, E.E.; Leijtens, J.P.; Wever, J.; van der Pol, J.M.; Willekens, F.G. )

    1989-12-01

    Coronary artery disease frequently occurs in combination with peripheral vascular disorders and is an important cause of morbidity and mortality during or after peripheral vascular surgery. However, the detection of coronary artery disease in patients with peripheral vascular disease may be complicated, since most of these patients are unable to perform conventional exercise testing. The authors report a sixty-two-year-old man with an infrarenally located aneurysm of the abdominal aorta who underwent thallium 201 scintigraphy combined with dipyridamole infusion as an alternative exercise test. The subsequent thallium 201 images showed perfusion defects indicative of severe coronary artery disease. Coronary angiography showed an occluded right coronary artery and a significant proximal stenosis in the left anterior descending coronary artery. The patient underwent successful aortocoronary bypass surgery, and two months later, the aortic aneurysm was operated on without complications. As a result, dipyridamole thallium 201 scintigraphy should be considered as a valuable diagnostic test to detect coronary artery disease in patients with peripheral vascular disorders.

  18. Leg edema from intrathecal opiate infusions.

    PubMed

    Aldrete, J A; Couto da Silva JM

    2000-01-01

    Despite the increasing popularity of intrathecal infusions to treat patients with long-term non-cancer-related pain, this therapy is not without serious side-effects. Five out of 23 patients who had intrathecal infusions of opiates for longer than 24 months developed leg and feet edema. As predisposing factors, cardiovascular disease, deep venous thrombosis, peripheral vascular disease, and venous stasis of the lower extremities were considered. Every patient who developed pedal and leg edema after the implantation of an infusion pump was also found to have leg edema and venous stasis prior to the time when the pump was inserted. This complication was severe enough to limit their physical activity, and to produce lymphedema, ulcerations and hyperpigmentation of the skin. Reduction of the edema occurred when the dose of the opiate was decreased, and in two cases in which the infusion was discontinued, there was almost complete resolution of the syndrome. It appears that the pre-existence of pedal edema and of venous stasis is a relative contraindication to the long-term intrathecal infusion of opiates in patients with chronic non-cancer pain.

  19. Neonatal vancomycin continuous infusion: still a confusion?

    PubMed

    Gwee, Amanda; Cranswick, Noel; Metz, David; Coghlan, Benjamin; Daley, Andrew J; Bryant, Penelope A; Curtis, Nigel

    2014-06-01

    Continuous infusions of vancomycin over 24 hours have been shown in adults to reduce drug toxicity, lower treatment costs and require fewer blood samples for therapeutic drug monitoring. They may also improve clinical outcome through earlier attainment of target drug concentrations. In neonates, there is no consensus on vancomycin dosing. We reviewed the literature to assess the evidence for vancomycin dosing regimens for continuous infusion in neonates. Medline and Embase were searched for studies about continuous vancomycin dosing regimens in neonates that reported serum drug concentrations. The search identified 469 articles, of which 5 were relevant. Five prospective studies were included; 2 studies used non-linear mixed effects modeling. Vancomycin was administered with parenteral nutrition or 5% dextrose. Target serum concentrations varied (range: 10-30 mg/L). F