[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.

Anaesthetic and ICU management of aneurysmal subarachnoid haemorrhage: a survey of European practice.

PubMed

Velly, Lionel J; Bilotta, Federico; Fàbregas, Neus; Soehle, Martin; Bruder, Nicolas J; Nathanson, Michael H

2015-03-01

Many aspects of the perioperative management of aneurysmal subarachnoid haemorrhage (SAH) remain controversial. It would be useful to assess differences in the treatment of SAH in Europe to identify areas for improvement. To determine the clinical practice of physicians treating SAH and to evaluate any discrepancy between practice and published evidence. An electronic survey. Physicians identified through each national society of neuroanaesthesiology and neurocritical care. A 31-item online questionnaire was distributed by the ENIG group. Questions were designed to investigate anaesthetic management of SAH and diagnostic and treatment approaches to cerebral vasospasm. The survey was available from early October to the end of November 2012. Completed surveys were received from 268 respondents, of whom 81% replied that aneurysm treatment was conducted early (within 24 h). Sixty-five percent of centres treated more than 60% of SAH by coiling, 19% had high-volume clipping (>60% of aneurysms clipped) and 16% used both methods equally. No clear threshold for arterial blood pressure target was identified during coiling, temporary clipping or in patients without vasospasm after the aneurysm had been secured. Almost all respondents used nimodipine (97%); 21% also used statins and 20% used magnesium for prevention of vasospasm. A quarter of respondents used intra-arterial vasodilators alone, 5% used cerebral angioplasty alone and 48% used both endovascular methods to treat symptomatic vasospasm. In high-volume clipping treatment centres, 58% of respondents used endovascular methods to manage vasospasm compared with 86% at high-volume coiling treatment centres (P < 0.001). The most commonly used intra-arterial vasodilator was nimodipine (82%), but milrinone was used by 23% and papaverine by 19%. More respondents (44%) selected 'triple-H' therapy over hypertension alone (30%) to treat vasospasm. We found striking variability in the practice patterns of European physicians involved in early treatment of SAH. Significant differences were noted among countries and between high and low-volume coiling centres.

Effect of hexamethonium on the vascular response to noradrenaline in man

PubMed Central

Hodge, R. L.; Whelan, R. F.

1962-01-01

Intra-arterial infusion of hexamethonium into the brachial artery had no potentiating effect on the constrictor response of the vessels of the forearm or hand to noradrenaline given by the same route. The response of the hand vessels to intravenous infusion of noradrenaline was enhanced after intra-arterial hexamethonium, but this was attributed to entry of the blocking agent into the general circulation resulting in blockade of baroreceptor reflexes since the potentiation was seen to an equal degree on both sides. It is concluded that if increased sensitivity to noradrenaline plays a part in the phenomenon of tolerance to hexamethonium this must be a slowly developing effect. PMID:13907950

Superselective Urokinase Infusion Therapy for Dorsalis Pedis Artery Occlusion in Buerger's Disease

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

Kubota, Yasushi; Kichikawa, Kimihiko; Uchida, Hideo

1997-09-15

Occlusion of the proximal left dorsalis pedis artery (DPA) in a patient with Buerger's disease was treated by continuous urokinase intraarterial infusion using a microcatheter. Recanalization of the DPA and healing of a toe ulcer were achieved. The patient remains asymptomatic during a 4-year follow-up.

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

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

Mitsudo, Kenji, E-mail: mitsudo@yokohama-cu.ac.j; Shigetomi, Toshio; Fujimoto, Yasushi

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 medianmore » 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.« less

Peripheral vascular effects of bretylium tosylate in man.

PubMed

Blair, D A; Glover, W E; Kidd, B S; Roddie, I C

1960-09-01

After intra-arterial infusion of bretylium tosylate (12.5 mg.), the reflex changes in vasoconstrictor tone which normally occur in the forearm with body cooling, positive pressure breathing, the Valsalva manoeuvre and postural change were greatly reduced or abolished. Reflex vasodilatation mediated by cholinergic fibres in response to body heating or to emotional stress was little affected. It was concluded that bretylium can selectively block the activity of sympathetic noradrenergic fibres without causing a similar block of sympathetic cholinergic fibres. As the responses to intravenous or intra-arterial infusions of adrenaline or noradrenaline were not reduced after bretylium, it was concluded that bretylium interferes with the activity of noradrenergic fibres rather than with the activity of the noradrenaline released at the nerve ending. After bretylium infusion, forearm and hand blood flow did not often rise to levels characteristic of full release of vasoconstrictor tone. As infusion of bretylium into a nerve-blocked forearm resulted in a pronounced reduction in flow, it is concluded that bretylium also has a constrictor effect on blood vessels. The state of the vessels following an infusion of bretylium appears to depend on the balance between this constrictor action and the longer-acting sympathetic blocking effect.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue.

PubMed

Salman, Rida; Sebaaly, Mikhael G; Wehbe, Mohammad Rachad; Sfeir, Pierre; Khalife, Mohamad; Al-Kutoubi, Aghiad

2017-06-01

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue

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

Salman, Rida; Sebaaly, Mikhael G.; Wehbe, Mohammad Rachad

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

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

Reproducibility of forearm vasodilator response to intra-arterial infusion of calcitonin gene-related peptide assessed by venous occlusion plethysmography

PubMed Central

Vanmolkot, Floris H M; de Hoon, Jan N J M

2005-01-01

Aims To assess the reproducibility of the forearm blood flow (FBF) response to intra-arterial infusion of calcitonin-gene related peptide (CGRP), measured by venous occlusion plethysmography. In addition, to compare different ways of expressing the FBF response and perform sample size calculations. Methods On two separate visits, CGRP (10 ng min−1 dl−1 forearm) was infused for 45 min into the brachial artery of six healthy subjects. Reproducibility was assessed by calculating mean difference, repeatability coefficient, within-subject coefficient of variation (WCV) and intraclass correlation coefficient. Results CGRP increased FBF from 2.8 ± 0.4 and 3.2 ± 0.7 (at baseline) to 15.4 ± 1.4 and 15.2 ± 1.5 ml min−1 dl−1 forearm (at 45 min) on visits 1 and 2, respectively (P < 0.0001 for both visits). Mean difference in FBF at 45 min between both visits was 0.3 ml min−1 dl−1 forearm (repeatability coefficient: 4.1 ml min−1 dl−1 forearm). This FBF response appeared to be more reproducible when expressed as absolute FBF in the infused arm (WCV 11%) compared with absolute FBF-ratio between both arms (WCV 37%), percentage change from baseline in FBF in the infused arm (WCV 29%) and percentage change from baseline in FBF-ratio (WCV 40%). When expressed as absolute FBF, a sample size of five (95% confidence interval: 2–12) subjects gives 90% power at a type I error probability of 0.05 to detect a 25% shift in FBF response. Conclusions Intra-arterial infusion of CGRP results in a forearm vasodilator response which is reproducible between days. This response is most reproducible when expressed as absolute FBF. The presented methodology provides a suitable pharmacodynamic model to assess the in vivo activity of CGRP-receptor antagonists in a small number of subjects. PMID:15801933

Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

PubMed

Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun; Ono, Minoru; Takahashi, Hiroyuki; Eriguchi, Masazumi

2014-06-01

A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that (10)BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

PubMed

Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

2018-06-16

To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P < 0.01), with fewer ophthalmic vascular events (early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P < 0.01), including peripheral retinal nonperfusion (5% vs. 2% per eye, P = 0.50), vitreous hemorrhage (9% vs. 2%, P = 0.20), subretinal hemorrhage (0% vs. 2%, P = 0.99), branch retinal vein occlusion (5% vs. 0%, P = 0.29), choroidal ischemia (14% vs. 4%, P = 0.14), and ophthalmic artery spasm/occlusion (27% vs. 0%, P < 0.01). Events did not correlate to patient age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era (2009-2011) through the current era (2012-2017) at this center. Experience performing this highly specialized procedure could be an important factor predicting IAC-related vascular events. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

[Intraarterial chemotherapy for uterine cervical adenocarcinoma: evaluation of its efficacy as neoadjuvant therapy].

PubMed

Usuki, N; Hirokawa, K; Tashiro, T; Saiwai, S; Miyamoto, T

1999-10-01

We performed preoperative intraarterial chemotherapy in twenty cases of uterine cervical adenocarcinoma (stage Ib: 2, II: 15, III: 3) and evaluated the efficacy of this therapy. The dosages used were 75-120 mg of CDDP, 10-20 mg of MMC and 30-60 mg of EPIR. These drugs were administered by intraarterial one-shot infusion twice every three weeks. In five cases, complete response (CR) of the primary lesion was confirmed by histologic examination. There were no cases of CR inpatients with well differentiated adenocarcinoma. Stage reduction was achieved in all cases except three. In all but one case, more than 50% volume reduction was recognized on MR images. These results were not significantly different from those in cases of uterine cervical squamous cell carcinoma in which we performed this therapy. Therefore, we concluded that intraarterial chemotherapy is highly effective and should be carried out as neoadjuvant therapy for advanced uterine cervical adenocarcinoma.

Intraarterial Infusion Of Erbitux and Bevacizumab For Relapsed/Refractory Intracranial Glioma In Patients Under 22

ClinicalTrials.gov

2018-01-26

Glioblastoma Multiforme; Fibrillary Astrocytoma of Brain; Glioma of Brainstem; Anaplastic Astrocytoma; Pilomyxoid Astrocytoma; Mixed Oligodendroglioma-Astrocytoma; Brain Stem Glioma; Diffuse Intrinsic Pontine Glioma

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

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

Weintraub, Joshua L., E-mail: Joshua.Weintraub@mssm.edu; Belanger, Adam R.; Sung, Chris C.

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 tomore » 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.« less

MRI evaluation of frequent complications after intra-arterial transplantation of mesenchymal stem cells in rats

NASA Astrophysics Data System (ADS)

Namestnikova, D.; Gubskiy, I.; Gabashvili, A.; Sukhinich, K.; Melnikov, P.; Vishnevskiy, D.; Soloveva, A.; Vitushev, E.; Chekhonin, V.; Gubsky, L.; Yarygin, K.

2017-08-01

Intra-arterial transplantation of mesenchymal stem cells (MSCs) is an effective delivery route for treatment of ischemic brain injury. Despite significant therapeutic effects and targeted cells delivery to the brain infraction, serious adverse events such as cerebral embolism have been reported and may restrict potential clinical applications of this method. In current study, we evaluate potential complications of intra-arterial MSCs administration and determine the optimum parameters for cell transplantation. We injected SPIO-labeled human MSCs via internal carotid artery with different infusion parameters and cell dose in intact rats and in rats with the middle cerebral occlusion stroke model. Cerebrovascular complications and labeled cells were visualized in vivo using MRI. We have shown that the incidence of cerebral embolic events depends on such parameters as cell dose, infusion rate and maintenance of blood flow in the internal carotid artery (ICA). Optimal parameters were considered to be 5×105 hMSC in 1 ml of PBS by syringe pump with velocity 100 μ/min and maintenance of blood flow in the ICA. Obtained data should be considered before planning experiments in rats and, potentially, can help in planning clinical trials in stroke patients.

Arterial infusion chemotherapy in patient with repeated recurrent tumor of cecal cancer: report of a case.

PubMed

Ogawa, Masaichi; Takao, Yoshihiko; Watanabe, Michiaki; Eto, Ken; Yamagata, Tetsuya; Ushigome, Takurou; Anazawa, Sadao; Yanaga, Katsuhiko

2008-12-01

We report a patient with a repeated recurrent tumor after Right-hemicolectomy for advanced cecal cancer who was treated by intra-arterial infusions of 5-fluorouracil (5-FU). A computed tomography scan revealed a pelvic mass involving the psoas major muscle and quadratos lumborum muscle, in contact with the widely projecting toward L2-S2. The fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed an accumulation spot in the same place. This case was deemed in operable, and one-shot bolus of 5-FU was administered through the tumor feeding arteries: the left 3rd, 4th lumbar, and ilio -- lumbar arteries at a dosage of 250 mg/body from each artery. A partial regression of the tumor was observed by computed tomography. The serum level of carbohydrate antigen 19-9 returned normal in 8 months. During chemotherapy, the side effect and complications were tolerable, and she experienced only grade-1 nausea caused by 5-fluorouracil. A long-time, intra-arterial 5-fluorouracil infusion could control effectively and safely.

Management of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Francoeur, Charles L; Mayer, Stephan A

2016-10-14

For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of current state-of-the-art care for DCI management.

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer.

PubMed

Hayashi, Yuichiro; Nakamura, Tatsuya; Mitsudo, Kenji; Kimura, Kanako; Yamaguchi, Hisashi; Ono, Takashi; Azami, Yusuke; Takayama, Kanako; Hirose, Katsumi; Yabuuchi, Tomonori; Suzuki, Motohisa; Hatayama, Yoshiomi; Kikuchi, Yasuhiro; Wada, Hitoshi; Fuwa, Nobukazu; Hareyama, Masato; Tohnai, Iwai

2017-10-01

The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. For all patients, the median follow-up was 25 months (range, 3-77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer. © 2016 John Wiley & Sons Australia, Ltd.

Potentiation of the NO-cGMP pathway and blood flow responses during dynamic exercise in healthy humans

PubMed Central

Limberg, Jacqueline K.; Malterer, Katherine R.; Kellawan, J. Mikhail; Schrage, William G.; Wilkins, Brad W.; Nicholson, Wayne T.; Eisenach, John H.; Joyner, Michael J.; Curry, Timothy B.

2017-01-01

Purpose Previous work has shown nitric oxide (NO) contributes to ~15% of the hyperemic response to dynamic exercise in healthy humans. This NO-mediated vasodilation occurs, in part, via increases in intracellular cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase. We sought to examine the effect of phosphodiesterase-5 (PDE-5) inhibition on forearm blood flow (FBF responses to dynamic handgrip exercise in healthy humans and the role of NO. We hypothesized exercise hyperemia would be augmented by sildenafil citrate (SDF, PDE-5 inhibitor). We further hypothesized any effect of SDF on exercise hyperemia would be abolished with intra-arterial infusion of the NO synthase (NOS) inhibitor L-NG-monomethyl arginine (L-NMMA). Methods FBF (Doppler ultrasound) was assessed at rest and during 5 minutes of dynamic forearm handgrip exercise at 15% of maximal voluntary contraction under control (saline) conditions and during 3 experimental protocols: 1) oral SDF (n=10), 2) intra-arterial L-NMMA (n=20), 3) SDF and L-NMMA (n=10). FBF responses to intra-arterial sodium nitroprusside (NTP, NO donor) were also assessed. Results FBF increased with exercise (p<0.01). Intra-arterial infusion of L-NMMA resulted in a reduction in exercise hyperemia (17±1 to 15±1 mL/dL/min, p<0.01). Although the hyperemic response to NTP was augmented by SDF (Area under the curve: 41±7 vs 61±11 AU, p<0.01), there was no effect of SDF on exercise hyperemia (p=0.33). Conclusions Despite improving NTP-mediated vasodilation, oral SDF failed to augment exercise hyperemia in young, healthy adults. These observations reflect a minor contribution of NO and the cGMP pathway during exercise hyperemia in healthy young humans. PMID:28013386

Rescue Therapy for Refractory Vasospasm after Subarachnoid Hemorrhage

PubMed Central

Durrant, Julia C.; Hinson, Holly E.

2014-01-01

Vasospasm and delayed cerebral ischemia remain to be the common causes of increased morbidity and mortality after aneurysmal subarachnoid hemorrhage. The majority of clinical vasospasm responds to hemodynamic augmentation and direct vascular intervention; however, a percentage of patients continue to have symptoms and neurological decline. Despite suboptimal evidence, clinicians have several options in treating refractory vasospasm in aneurysmal subarachnoid hemorrhage (aSAH), including cerebral blood flow enhancement, intra-arterial manipulations, and intra-arterial and intrathecal infusions. This review addresses standard treatments as well as emerging novel therapies aimed at improving cerebral perfusion and ameliorating the neurologic deterioration associated with vasospasm and delayed cerebral ischemia. PMID:25501582

Hepatic metastases of colorectal cancer: locoregional intra-arterial treatment.

PubMed

Pasetto, Lara Maria; Merenda, Roberto; Pilati, Pierluigi; Sinigaglia, Giulietta; Monfardini, Silvio

2006-01-01

A radical resection alone of colorectal hepatic metastases is possible in only 10-20% of the patients but, when resection and ablation are combined, the rate of radicalism can improve. A regional hepatic intra-arterial chemotherapy infusion (HAI) has been introduced in the clinical practice, as a possible alternative approach to systemic chemotherapy. Nevertheless, the introduction of new systemic therapies with monoclonal antibodies, combined to irinotecan or oxaliplatin, recently improved response rates and overall survival ia these patients. Aiming to evaluate a possible influence of HAI in these new treatments, the most important studies underlining the evolution of intrahepatic administration in recent years are reviewed.

Nimodipine alters acquisition of a visual discrimination task in chicks.

PubMed

Deyo, R; Panksepp, J; Conner, R L

1990-03-01

Chicks 5 days old received intraperitoneal injections of nimodipine 30 min before training on either a visual discrimination task (0, 0.5, 1.0, or 5.0 mg/kg) or a test of separation-induced distress vocalizations (0, 0.5, or 2.5 mg/kg). Chicks receiving 1.0 mg/kg nimodipine made significantly fewer visual discrimination errors than vehicle controls by trials 41-60, but did not differ from controls 24 h later. Chicks in the 5 mg/kg group made significantly more errors when compared to controls both during acquisition of the task and during retention. Nimodipine did not alter separation-induced distress vocalizations at any of the doses tested, suggesting that nimodipine's effects on learning cannot be attributed to a reduction in separation distress. These data indicate that nimodipine's facilitation of learning in young subjects is dose dependent, but nimodipine failed to enhance retention.

[The clinical effect of combination therapy for oral cancer with S-1, superselective intra-arterial chemotherapy, and radiation therapy].

PubMed

Yamamoto, Chika; Yoshikawa, Hiromasa; Fukumoto, Shunsuke; Higuchi, Takashi; Yoshida, Masanori; Horinouchi, Yasufumi; Uehara, Satoru; Yasumori, Koutarou

2011-12-01

Combination therapy with S-1, superselective intra-arterial infusion of CBDCA and radiation therapy has been used to treat patients with oral cancer since 2005. In this study, the histopathological effects and toxicities following concurrent chemoradiotherapy were examined. The subjects consisted of 15 patients (10 men and 5 women) who were treated with S-1 (60-80 mg/day, 4 weeks), superselective intra-arterial infusion of CBDCA (300 mg/body) and radiation therapy (total dose 30-36 Gy) in our department from 2005 to 2009. Nine patients, showed T2 disease, 3 showed T3 disease, and another 3 showed T4 diseases. The primary cancer sites were the tongue (6 cases), buccal mucosa (4 cases), mandible gingival (3 cases), maxillary gingiva (1 case), and the floor of the mouth (1 case). The histopathological effects were evaluated according to Oboshi-Shimosato classification. Grade IV was shown in 10 cases (66. 7%), grade III in 1 case (6. 7%), II bin 3 cases (20. 0%), and II a in 1 case (6. 7%). All patients completed the treatment. The pathological response of the resected tumor was grade IIbor higher in 14 cases (93. 3%). While good histological effects were noted, there was one patient for whom viable tumor cells remained in the central part of the tumor. The present study indicates that further investigation is needed to determine the best dosing and dosing schedule.

Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II.

PubMed

Goldberg, J A; Bradnam, M S; Kerr, D J; McKillop, J H; Bessent, R G; McArdle, C S; Willmott, N; George, W D

1987-12-01

As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.

The nicorandil-induced vasodilation in humans is inhibited by miconazole.

PubMed

Ueda, Keiko; Goto, Chikara; Jitsuiki, Daisuke; Umemura, Takashi; Nishioka, Kenji; Kimura, Masashi; Noma, Kensuke; Nakagawa, Keigo; Oshima, Tetsuya; Yoshizumi, Masao; Chayama, Kazuaki; Higashi, Yukihito

2005-04-01

Nicorandil, N-(2-hydroxyethyl)-nicotinamide nitrate, exerts its vasodilatory effects by opening ATP-sensitive potassium (K-ATP) channels and by acting as the exogenous nitric oxide (NO). It is not clear, however, whether the actions of other endothelium-dependent vasodilators, such as NO, endothelium-derived hyperpolarizing factor (EDHF), and prostaglandins, contribute to nicorandil-induced vasodilation in the vasculature in humans. We evaluated forearm blood flow (FBF) response to intraarterial infusion of nicorandil alone and in the presence of glibenclamide, a K-ATP channel inhibitor, N(G)-monomethyl-L-arginine, an NO synthase inhibitor, indomethacin, a cyclooxygenase inhibitor, or miconazol, a cytochrome P-450 inhibitor, in 24 healthy male subjects. FBF was measured using strain-gauge plethysmography. Infusion of nicorandil significantly increased the FBF response in a dose-dependent manner. Intraarterial infusion of glibenclamide attenuated nicorandil-induced vasodilation (160.9 +/- 21.2% versus 90.2 +/- 19.4%, P < 0.01), and miconazole also attenuated the FBF response to nicorandil (160.9 +/- 21.2% versus 66.1 +/- 9.2%, P < 0.001). N-monomethyl-L-arginine or indomethacin did not alter the FBF response to nicorandil. These findings suggest that nicorandil causes vasodilation in forearm circulation in humans, at least in part through a pathway that is dependent on K-ATP channels and cytochrome P-450, but not on endogenous NO and prostaglandins. EDHF may contribute to nicorandil-induced vasodilation in humans.

Intracranial Biodegradable Silica-Based Nimodipine Drug Release Implant for Treating Vasospasm in Subarachnoid Hemorrhage in an Experimental Healthy Pig and Dog Model

PubMed Central

Koskimäki, Janne; Tarkia, Miikka; Ahtola-Sätilä, Tuula; Saloranta, Lasse; Laakso, Aki; Frantzén, Janek

2015-01-01

Nimodipine is a widely used medication for treating delayed cerebral ischemia (DCI) after subarachnoid hemorrhage. When administrated orally or intravenously, systemic hypotension is an undesirable side effect. Intracranial subarachnoid delivery of nimodipine during aneurysm clipping may be more efficient way of preventing vasospasm and DCI due to higher concentration of nimodipine in cerebrospinal fluid (CSF). The risk of systemic hypotension may also be decreased with intracranial delivery. We used animal models to evaluate the feasibility of surgically implanting a silica-based nimodipine releasing implant into the subarachnoid space through a frontotemporal craniotomy. Concentrations of released nimodipine were measured from plasma samples and CSF samples. Implant degradation was followed using CT imaging. After completing the recovery period, full histological examination was performed on the brain and meninges. The in vitro characteristics of the implant were determined. Our results show that the biodegradable silica-based implant can be used for an intracranial drug delivery system and no major histopathological foreign body reactions were observed. CT imaging is a feasible method for determining the degradation of silica implants in vivo. The sustained release profiles of nimodipine in CSF were achieved. Compared to a traditional treatment, higher nimodipine CSF/plasma ratios can be obtained with the implant. PMID:25685803

Development and Evaluation of High Bioavailable Sustained-Release Nimodipine Tablets Prepared with Monolithic Osmotic Pump Technology.

PubMed

Kong, Hua; Yu, Fanglin; Liu, Yan; Yang, Yang; Li, Mingyuan; Cheng, Xiaohui; Hu, Xiaoqin; Tang, Xuemei; Li, Zhiping; Mei, Xingguo

2018-01-01

Frequent administration caused by short half-life and low bioavailability due to poor solubility and low dissolution rate limit the further application of poorly water-soluble nimodipine, although several new indications have been developed. To overcome these shortcomings, sophisticated technologies had to be used since the dose of nimodipine was not too low and the addition of solubilizers could not resolve the problem of poor release. The purpose of this study was to obtain sustained and complete release of nimodipine with a simple and easily industrialized technology. The expandable monolithic osmotic pump tablets containing nimodipine combined with poloxamer 188 and carboxymethylcellulose sodium were prepared. The factors affecting drug release including the amount of solubilizing agent, expanding agent, retarding agent in core tablet and porogenic agent in semipermeable film were optimized. The release behavior was investigated both in vitro and in beagle dogs. It was proved that the anticipant release of nimodipine could be realized in vitro. The sustained and complete release of nimodipine was also realized in beagles because the mean residence time of nimodipine from the osmotic pump system was longer and Cmax was lower than those from the sustained-release tablets in market while there was no difference in AUC(0-t) of the monolithic osmotic pump tablets and the sustained release tablets in market. It was reasonable to believe that the sustained and complete release of poorly watersoluble nimodipine could be realized by using simple expandable monolithic osmotic pump technology combined with surfactant. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study

PubMed Central

Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

2017-01-01

Objective: To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Materials and Methods: Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Results: Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. Conclusion: We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron. PMID:28553371

Effect of Nimodipine on Morphine-related Withdrawal Syndrome in Rat Model: An Observational Study.

PubMed

Mishra, Pravash Ranjan; Barik, Mayadhar; Ray, Subrata Basu

2017-01-01

To observe the effect of L-type calcium channel blocker like nimodipine on morphine's withdrawal when it was administered continuously along with morphine versus a single bolus dose of nimodipine, which was administered at the end of the experiment before the precipitation of withdrawal reaction in morphine-dependent rats. Four groups of adult male Wistar rats were rendered morphine dependent by subcutaneous injections of morphine at a dose of 10 mg/kg for 10 days. Nimodipine 10 mg/kg intraperitoneally (ip) administered to one group once daily before morphine administration in the entire experimental period, and another group received nimodipine only once at the end of the experiment as a single bolus dose 2 mg/kg before the administration of naloxone. Naloxone 3 mg/kg was administered ip to all the groups to precipitate withdrawal reactions. The withdrawal reactions were evaluated and scored as per the Gellert and Holtzman global withdrawal rating scale. Nimodipine when administered as a single bolus dose before naloxone administration in morphine-dependant rats reduced the features of withdrawal reactions more effectively than continuous administration of nimodipine along with morphine throughout the experimental period. We discovered that nimodipine helps in attenuating the severity of morphine withdrawal having potential role encountered during pharmacotherapy with morphine management of opioid dependence, well memory, impairement, cell signaling and phosphorylation of neuron.

Simple and validated UHPLC-MS/MS analysis of nimodipine in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage.

PubMed

Mohamed, Susan; Riva, Roberto; Contin, Manuela

2016-08-15

We present a simple, fast and validated method for the determination of nimodipine in plasma and cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Plasma or CSF 250μL aliquots were pretreated with acetonitrile spiked with lacosamide as internal standard. The chromatographic separation was performed on a Fusion (3μm) 50×2.0mm I.D. column with gradient elution of 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile at a flow rate of 0.35mL/min. The MS/MS ion transitions were 419.1→343 for nimodipine and 251.1→91 for the internal standard. The linearity was determined from 2.0 to 40.0ng/mL in plasma and 40.0-800.0pg/mL in CSF. The lower limit of quantitation (LLOQ) of nimodipine was 0.4ng/mL in plasma and 40pg/mL in CSF. The mean recovery for nimodipine was ≥75% in plasma and ≥90% in CSF at all three considered concentrations. Intra- and interassay precision and accuracy were ≤15% at all quality control concentrations in plasma and CSF. The method was applied to measure plasma and CSF concentrations of nimodipine in a series of patients with subarachnoid haemorrhage treated with intravenous nimodipine. The present procedure, omitting time-consuming liquid-liquid extraction and drying steps, is faster, simpler and cheaper than published LC-MS/MS analytical methods for nimodipine in plasma and the first validated one for nimodipine in CSF. Copyright © 2016 Elsevier B.V. All rights reserved.

Intra-arterial bromodeoxyuridine radiosensitization of malignant gliomas

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

Hegarty, T.J.; Thornton, A.F.; Diaz, R.F.

1990-08-01

In the 1950's it was first observed that mammalian cells exposed to the halogenated deoxyuridines were more sensitive to ultraviolet light and radiation than untreated cells. This prompted early clinical trials with bromodeoxyuridine (BUdR) which showed mixed results. More recently, several Phase I studies, while establishing the feasibility of continuous intravenous (IV) infusion of BUdR, have reported significant dose limiting skin and bone marrow toxicities and have questioned the optimal method of BUdR delivery. To exploit the high mitotic activity of malignant gliomas relative to surrounding normal brain tissue, we have developed a permanently implantable infusion pump system for safe,more » continuous intraarterial (IA) internal carotid BUdR delivery. Since July 1985, 23 patients with malignant brain tumors (18 grade 4, 5 grade 3) have been treated in a Phase I clinical trial using IA BUdR (400-600 mg/m2/day X 8 1/2 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy/day in 6 1/2 weeks). Following initial biopsy/surgery the infusion pump system was implanted; BUdR infusion began 2 weeks prior to and continued throughout the 6 1/2 week course of radiotherapy. There have been no vascular complications. Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Myelosuppression requiring dose reduction occurred in one patient. An overall Kaplan-Meier estimated median survival of 20 months has been achieved. As in larger controlled series, histologic grade and age are prognostically significant. We have shown in a Phase I study that IA BUdR radiosensitization is safe, tolerable, may lead to improved survival, and appears to be an efficacious primary treatment of malignant gliomas.« less

Rationale and design of a double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of nimodipine in preventing cognitive impairment in ischemic cerebrovascular events (NICE)

PubMed Central

2012-01-01

Background Stroke is the second most common cause of mortality and the leading cause of neurological disability, cognitive impairment and dementia worldwide. Nimodipine is a dihydropyridinic calcium antagonist with a role in neuroprotection, making it a promising therapy for vascular cognitive impairment and dementia. Methods/design The NICE study is a multicenter, randomized, double-blind, placebo-controlled study being carried out in 23 centers in China. The study population includes patients aged 30–80 who have suffered an ischemic stroke (≤7 days). Participants are randomly allocated to nimodipine (90 mg/d) or placebo (90 mg/d). The primary efficacy is to evaluate the level of mild cognitive impairment following treatment of an ischemic stroke with nimodipine or placebo for 6 months. Safety is being assessed by observing side effects of nimodipine. Assuming a relative risk reduction of 22%, at least 656 patients are required in this study to obtain statistical power of 90%. The first patient was recruited in November 2010. Discussion Previous studies suggested that nimodipine could improve cognitive function in vascular dementia and Alzheimer’s disease dementia. It is unclear that at which time-point intervention with nimodipine should occur. Therefore, the NICE study is designed to evaluate the benefits and safety of nimodipine, which was adminstered within seven days, in preventing/treating mild cognitive impairment following ischemic stroke. PMID:22950711

[Nimodipine in ischemic cerebropathy].

PubMed

Di Lascio, G; Salvini, S

1993-02-01

Fifty patients of either sex with acute and chronic cerebrovascular disorders were submitted to an observation protocol and treated with oral nimodipine (tablets or drops) at a daily dosage of 90 mg for 1 to 3 months. Nimodipine proved useful both from the therapeutic point of view and for its easy handling in acute pathology (TIA, RIND, minor stroke, complete stroke) as well as chronic cerebral ischemia. The drug was well tolerated both locally and systemically; in patients with concomitant arterial hypertension, nimodipine reduced blood pressure with a tendency towards stabilization at near-normal levels.

Tromboxane B2 inhibits the pulmonary inactivation of prostaglandin E2 in the dog.

PubMed Central

Fitzpatrick, T. M.; Friedman, L. S.; Kot, P. A.; Ramwell, P. W.

1980-01-01

1 The systemic vasodepressor response to intravenously administered prostaglandin E2 (PGE2, 0.3, 1.0 and 3.0 micrograms/kg) is potentiated during intravenous infusion of thromboxane B2 (TXB2, 1.0 micrograms kg-1 min-1) in the anaesthetized dog. 2 The augmented haemodynamic response returns toward control values following cessation of the TXB2 infusion. 3 The systemic haemodynamic responses to intra-arterially administered PGE2, PGF2 alpha and PGI2 as well as intravenously administered PGF2 alpha and PGI2 are not altered by TXB2 infusion. 4. This study suggests that TXB2 inhibits the pulmonary inactivation of PGE2. 5 Arachidonic acid metabolites may interact, producing haemodynamic responses differing from their individual effects. PMID:7000216

Feasibility and Safety of Intra-arterial Pericyte Progenitor Cell Delivery Following Mannitol-Induced Transient Blood-Brain Barrier Opening in a Canine Model.

PubMed

Youn, Sung Won; Jung, Keun-Hwa; Chu, Kon; Lee, Jong-Young; Lee, Soon-Tae; Bahn, Jae-jun; Park, Dong-Kyu; Yu, Jung-Suk; Kim, So-Yun; Kim, Manho; Lee, Sang Kun; Han, Moon-Hee; Roh, Jae-Kyu

2015-01-01

Stem cell therapy is currently being studied with a view to rescuing various neurological diseases. Such studies require not only the discovery of potent candidate cells but also the development of methods that allow optimal delivery of those candidates to the brain tissues. Given that the blood-brain barrier (BBB) precludes cells from entering the brain, the present study was designed to test whether hyperosmolar mannitol securely opens the BBB and enhances intra-arterial cell delivery. A noninjured normal canine model in which the BBB was presumed to be closed was used to evaluate the feasibility and safety of the tested protocol. Autologous adipose tissue-derived pericytes with platelet-derived growth factor receptor β positivity were utilized. Cells were administered 5 min after mannitol pretreatment using one of following techniques: (1) bolus injection of a concentrated suspension, (2) continuous infusion of a diluted suspension, or (3) bolus injection of a concentrated suspension that had been shaken by repeated syringe pumping. Animals administered a concentrated cell suspension without mannitol pretreatment served as a control group. Vital signs, blood parameters, neurologic status, and major artery patency were kept stable throughout the experiment and the 1-month posttreatment period. Although ischemic lesions were noted on magnetic resonance imaging in several mongrel dogs with concentrated cell suspension, the injection technique using repeated syringe shaking could avert this complication. The cells were detected in both ipsilateral and contralateral cortices and were more frequent at the ipsilateral and frontal locations, whereas very few cells were observed anywhere in the brain when mannitol was not preinjected. These data suggest that intra-arterial cell infusion with mannitol pretreatment is a feasible and safe therapeutic approach in stable brain diseases such as chronic stroke.

Efficacy of Nimodipine Plus Yufeng Ningxin Tablets for Patients with Frequent Migraine.

PubMed

Mu, Hongmei; Wang, Liyong

2018-06-07

To test the effects of Nimodipine plus Yufeng Ningxin tablets on frequent migraine. Two hundred forty-two patients with frequent migraine were divided into the control group with those consuming Flunarizine (120 cases) and the treatment group with those consuming Nimodipine plus Yufeng Ningxin tablets (122 cases). The course of frequent migraine treatment lasted 7 weeks. The number of migraine days, visual analogue scale (VAS) score, and response rate were measured. There was significant difference in the cure rate as the Nimodipine plus Yufeng Ningxin tablets group compared with the Flunarizine group (78.7 vs. 21.7%; p < 0.001). Fewer migraine days and VAS score were observed in the treatment group when compared with the control group (p < 0.05). Nimodipine plus Yufeng Ningxin tablets were superior to Flunarizine in terms of the response rate at week 7 (p < 0.05). Due to its high cure rate, treatment with Nimodipine plus Yufeng Ningxin tablets is recommended to control frequent migraine, and this hypothesis needs to be confirmed through further studies conducted on a more extensive population. © 2018 S. Karger AG, Basel.

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.

PubMed

Stiefel, Michael F; Heuer, Gregory G; Abrahams, John M; Bloom, Stephanie; Smith, Michelle J; Maloney-Wilensky, Eileen; Grady, M Sean; LeRoux, Peter D

2004-10-01

Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Effect of piracetam and nimodipine on full-thickness skin burns in rabbits.

PubMed

Sari, Elif; Dincel, Gungor C

2016-08-01

The potential of several drugs for full-thickness skin burns has been investigated, but the treatment of such burns remains a challenge in plastic surgery. The present study was designed to determine the effect of systemic and topical administration of piracetam and nimodipine on full-thickness skin burn wound healing. A total of 36 New Zealand male rabbits were divided into six groups. Full-thickness skin burns were produced in all the groups, except the control group. Piracetam was administered systemically (piracetam-IV) and topically (piracetam-C) for 14 days, and nimodipine was administered systemically (nimodipine-IV) and topically (nimodipine-C) over the burn wounds for 14 days. The sham group underwent burn injury but was not administered any drug. After 21 days, gross examination and histopathological analysis were performed and the results were compared statistically. Nimodipine-C and nimodipine-IV had no effect on burn wound healing. However, both piracetam-IV and piracetam-C significantly enhanced the healing of the full-thickness skin burn wounds, although the latter was more effective, useful and practical in burn wound healing. The histopathological features of the wounds in the piracetam-C group were closer to those of the control group than those of the other groups. Piracetam-C rather than piracetam-IV may promote full-thickness burn wound healing in rabbits. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

[The effect of nimodipine on cochlear blood flow in the guinea pig].

PubMed

Meyer, P; Werner, E; Schmidt, R; Grützmacher, W; Gehrig, W; Seuter, F

1994-10-01

The influence of nimodipine (Nimotop, CAS 66085-59-4), a selectively cerebrovascularly acting 1,4-dihydropyridine calcium antagonist, on the cochlear blood flow (CBF) was studied in 19 guinea pigs (6 controls). The hydrogen clearance measurements were carried out under alpha-chloralose-ethylurethane anaesthesia, artificial respiration with simultaneous control of electrocardiogram, blood pressure, body temperature and arterial pH (hourly). The indirect measurement of CBF was carried out by means of hydrogen clearance in the perilymphatic space (basal turn) before and after intravenous application of 1 microgram nimodipine/kg/min. The mean arterial blood pressure remained within the +/- 5% range of the initial value during the experiment. Under treatment with nimodipine the CBF showed a non-significant average increase of 4.69% and under placebo (20% ethanol, 17% polyethylenglycol 400, citrate buffer), a non-significant average decrease of 6.16%. The influence of nimodipine on CBF was underlined by the overcompensation of the placebo effect.

Antileishmanial activity and ultrastructural alterations of Leishmania (L.) chagasi treated with the calcium channel blocker nimodipine.

PubMed

Tempone, André Gustavo; Taniwaki, Noemi Nosomi; Reimão, Juliana Quero

2009-08-01

In a search for novel antileishmanial drugs, we investigated the activity of the calcium channel blocker nimodipine against Leishmania spp. and explored the ultrastructural damages of parasites induced by nimodipine after a short period of incubation. Nimodipine was highly effective against promastigotes and intracellular amastigotes of Leishmania (L.) chagasi, with 50% inhibitory concentration values of 81.2 and 21.5 muM, respectively. Nimodipine was about fourfold more effective than the standard pentavalent antimony against amastigotes and showed a Selectivity Index of 4.4 considering its mammalian cells toxicity. Leishmania (L.) amazonensis and Leishmania (L.) major promastigotes were also susceptible to nimodipine in a range concentration between 31 and 128 muM. Ultrastructural studies of L. (L.) chagasi revealed intense mitochondria damage and plasma membrane blebbing, resulting in a leishmanicidal effect as demonstrated by the lack of mitochondrial oxidative metabolism. The amastigote-killing effect suggests other mechanism than macrophage activation, as no upregulation of nitric oxide was seen. This calcium channel blocker is an effective in vitro antileishmanial compound and if adequately studied could be used as a novel drug candidate or as a novel drug lead compound for drug design studies against leishmaniasis.

The effect of nimodipine on memory impairment during spontaneous morphine withdrawal in mice: Corticosterone interaction.

PubMed

Vaseghi, Golnaz; Rabbani, Mohammed; Hajhashemi, Valiollah

2012-11-15

Effects of the nimodipine, L-type calcium channel antagonist, has been studied on memory loss caused by spontaneous morphine withdrawal in mice. Mice were made dependent by increasing doses of morphine over three days. Memory was evaluated using object recognition task, which is based on tendency of rodents to exploration of new objects. The test was comprised of three sections: 15 min habitation, 12 min first trial and 5 min test trial. Recognition index was evaluated 4h after the last dose of morphine. Nimodipine was administrated either in chronic form (1, 5 and 10mg/kg) with daily doses of morphine or it was given as a single injection (5 and 10mg/kg) on the last day. Nimodipine in both treatment forms prevented the memory impairment following spontaneous morphine withdrawal. Corticosterone concentration was increased in brain and blood of mice during abstinence phase and pretreatment with nimodipine prevented the increase in brain and blood corticosterone concentration. The results show that blockade of L-type calcium channels improves memory deficits caused by morphine withdrawal. This indicates that some kind of treatments, such as nimodipine, administrated over the acute withdrawal phase, can prevent memory deficit during withdrawal. Copyright © 2012 Elsevier B.V. All rights reserved.

Solid dispersions in the development of a nimodipine floating tablet formulation and optimization by artificial neural networks and genetic programming.

PubMed

Barmpalexis, Panagiotis; Kachrimanis, Kyriakos; Georgarakis, Emanouil

2011-01-01

The present study investigates the use of nimodipine-polyethylene glycol solid dispersions for the development of effervescent controlled release floating tablet formulations. The physical state of the dispersed nimodipine in the polymer matrix was characterized by differential scanning calorimetry, powder X-ray diffraction, FT-IR spectroscopy and polarized light microscopy, and the mixture proportions of polyethylene glycol (PEG), polyvinyl-pyrrolidone (PVP), hydroxypropylmethylcellulose (HPMC), effervescent agents (EFF) and nimodipine were optimized in relation to drug release (% release at 60 min, and time at which the 90% of the drug was dissolved) and floating properties (tablet's floating strength and duration), employing a 25-run D-optimal mixture design combined with artificial neural networks (ANNs) and genetic programming (GP). It was found that nimodipine exists as mod I microcrystals in the solid dispersions and is stable for at least a three-month period. The tablets showed good floating properties and controlled release profiles, with drug release proceeding via the concomitant operation of swelling and erosion of the polymer matrix. ANNs and GP both proved to be efficient tools in the optimization of the tablet formulation, and the global optimum formulation suggested by the GP equations consisted of PEG=9%, PVP=30%, HPMC=36%, EFF=11%, nimodipine=14%. Copyright © 2010 Elsevier B.V. All rights reserved.

Endovascular Management of Central Retinal Arterial Occlusion.

PubMed

Agarwal, Nitin; Gala, Nihar B; Baumrind, Benjamin; Hansberry, David R; Thabet, Ahmad M; Gandhi, Chirag D; Prestigiacomo, Charles J

2016-11-01

Central retinal artery occlusion (CRAO) is an ophthalmologic emergency due to the sudden cessation of circulation to the inner retinal layer. Without immediate treatment, permanent blindness may ensue. Several treatment options exist, ranging from noninvasive medical management to thrombolysis. Nonetheless, ongoing debate exists regarding the best therapeutic strategy. The authors present the case of a 78-year-old woman with a medical history of hypercholesterolemia and rheumatoid arthritis who experienced complete loss of vision in her left eye. Following ophthalmologic evaluation demonstrating left CRAO, anterior chamber paracentesis was performed. Endovascular intervention was performed via local intra-arterial fibrinolysis with alteplase. Her vision returned to 20/20 following the procedure. In general, conventional therapies have not significantly improved patient outcomes. Several management options exist for CRAO. In general, conservative measures have not been reported to yield better patient outcomes as compared to the natural history of this medical emergency. Endovascular approaches are another option as observed with this case reported. In cases of CRAO, therapeutic strategies such as intra-arterial fibrinolysis utilize a local infusion of reactive tissue plasminogen activator directly at the site of occlusion via catheterization of the ophthalmic artery. Although several case series do show promising results after treating CRAO with intra-arterial fibrinolysis, further studies are required given the reports of complications.

Hemodynamic management and outcome of patients treated for cerebral vasospasm with intraarterial nicardipine and/or milrinone.

PubMed

Schmidt, Ulrich; Bittner, Edward; Pivi, Silvia; Marota, John J A

2010-03-01

Vasospasm is a potentially devastating complication after aneurysmal subarachnoid hemorrhage. Although endovascular treatment with intraarterial nicardipine and milrinone is an accepted clinical treatment strategy, there is little information either on hemodynamic management during treatment or on outcome and consequences of the hemodynamic management. We tested 2 hypotheses: (1) intraarterial administration of nicardipine and milrinone to treat cerebral vasospasm would require increased administration of vasoconstrictor to support arterial blood pressure at target levels; and (2) high-dose vasopressors administered to increase blood pressure in these patients would lead to systemic acidosis and end-organ ischemic damage. We conducted a single-center, retrospective review of consecutive patients with clinically symptomatic vasospasm after aneurysmal subarachnoid hemorrhage that failed medical management with "triple H therapy" and subsequently received intraarterial nicardipine and/or milrinone between March 2005 and July 2007. Of 160 endovascular interventions in 73 patients (aged 52 +/- 10 years; 50 women), 96 received only nicardipine, 5 only milrinone, and 59 both drugs. General anesthesia with muscle relaxation was performed for 93% of procedures. During treatment, both the number and dose of vasopressors required to maintain arterial blood pressure at target levels increased; the median dose of phenylephrine increased from 200 (n = 121) to 325 microg/min (n = 122), norepinephrine increased from 12 (n = 60) to 24.5 microg/min (n = 87), and vasopressin infusions increased from 7 to 24. Nonetheless, arterial blood pressure decreased 13% during treatment. In >90% of procedures, the postprocedure angiogram showed improved vessel caliber. A single patient demonstrated troponin T increase; no patients had a decrease in renal function, bowel or peripheral ischemia, systemic acidosis, or acute stroke. Overall mortality was 11%. Intraarterial administration of nicardipine and/or milrinone requires use of vasopressors to maintain arterial blood pressure. Despite high doses of vasoconstrictors, treatment has low mortality, minimal end-organ ischemic damage or systemic acidosis, and results in improved caliber of cerebral vessels affected by vasospasm.

Real-time hemodynamic response and mitochondrial function changes with intracarotid mannitol injection

PubMed Central

Joshi, Shailendra; Singh-Moon, Rajinder; Wang, Mei; Bruce, Jeffrey N.; Bigio, Irving J.; Mayevsky, Avraham

2014-01-01

Disruption of blood brain barrier (BBB) is used to enhance chemotherapeutic drug delivery. The purpose of this study was to understand the time course of hemodynamic and metabolic response to intraarterial (IA) mannitol infusions in order to optimize the delivery of drugs for treating brain tumors. Principal results We compared hemodynamic response, EEG changes, and mitochondrial function as judged by relative changes in tissue NADH concentrations, after intracarotid (IC) infusion of equal volumes of normal saline and mannitol in our rabbit IC drug delivery model. We observed significantly greater, though transient, hyperemic response to IC infusion of mannitol compared to normal saline. Infusion of mannitol also resulted in a greater increase in tissue NADH concentrations relative to the baseline. These hemodynamic, and metabolic changes returned to baseline within 5 min of mannitol injection. Conclusion Significant, though transient, changes in blood flow and brain metabolism occur with IA mannitol infusion. The observed transient hyperemia would suggest that intravenous (IV) chemotherapy should be administered either just before, or concurrent with IA mannitol injections. On the other hand, IA chemotherapy should be delayed until the peak hyperemic response has subsided. PMID:24440631

Effect of pyrrolidone-pyroglutamic acid composition on blood flow in rat middle cerebral artery.

PubMed

Semkina, G A; Matsievskii, D D; Mirzoyan, N R

2006-01-01

We compared the effects of a pyrrolidone-pyroglutamic acid composition and nimodipine on blood circulation in the middle cerebral artery in rats. The composition produced a strong effect on blood supply to the brain, stimulated blood flow in the middle cerebral artery (by 60 +/- 9%) and decreased blood pressure (by 25.0 +/- 2.7%). The cerebrovascular effects of this composition differed from those of nimodipine. Nimodipine not only increased middle cerebral artery blood flow, but also decreased cerebral blood flow in the early period after treatment.

Practical Vascular Anatomy in the Preparation of Radioembolization

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

Paprottka, P. M., E-mail: philipp.paprottka@med.uni-muenchen.de; Jakobs, T. F., E-mail: tobias.jakobs@barmherzige-muenchen.de; Reiser, M. F.

2012-06-15

As the incidence of primary and metastatic liver cancer continues to increase, the use of minimally invasive techniques as a treatment option is becoming more common. Radioembolization, a form of intra-arterial brachytherapy, is a technique where particles of glass or resin, impregnated with the isotope {sup 90}yttrium ({sup 90}Y), are infused through a catheter directly into the hepatic arteries. This modality is based on the fact that hepatic malignancies receive their blood supply from the hepatic artery, whereas normal hepatocytes are perfused mostly from the portal circulation, which allows delivery of high doses to the tumor vasculature with relative sparingmore » of normal liver tissue. This has been shown to be effective for both primary and metastatic tumors. A variety of complications may be related to hepatic intra-arterial treatments, especially to the gastroduodenal region. These complications are known to come from inadvertent extrahepatic infusion of {sup 90}Y particles, through arteries originating from the hepatic arterial branches such as the falciform artery, cystic artery, arteries from the pancreaticoduodenal arcade, gastroduodenal artery, or right gastric artery. Surgeons and interventional radiologists rely on accurate imaging and assessment of the hepatic arterial supply. It is important to know the common anatomic variations and technical considerations before radioembolization. We recommend an aggressive occlusion of all the above-mentioned arteries; further, clinicians should watch out for any other aberrant branches, and if in doubt, they ought to be coiled.« less

Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

PubMed

Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

2008-08-07

The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients

PubMed Central

Tartara, A.; Galimberti, C.A.; Manni, R.; Parietti, L.; Zucca, C.; Baasch, H.; Caresia, L.; Mück, W.; Barzaghi, N.; Gatti, G.; Perucca, E.

1991-01-01

1 The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively. 2 Compared with the values found in the control group, mean areas under the plasma nimodipine concentration curve were lowered by about seven-fold (P < 0.01) in patients taking enzyme-inducing anticonvulsants and increased by about 50% (P < 0.05) in patients taking sodium valproate. 3 Nimodipine half-lives were shorter in enzyme-induced patients than in controls (3.9 ± 2.0 h vs 9.1 ± 3.4 h, means ± s.d., P < 0.01), but this difference could be artifactual since in the patients drug concentrations declined rapidly below the limit of assay, thus preventing identification of a possible slower terminal phase. In valproate-treated patients, half-lives (8.2 ± 1.8 h) were similar to those found in controls. PMID:1777370

Development of two step liquid-liquid extraction tandem UHPLC-MS/MS method for the simultaneous determination of Ginkgo flavonoids, terpene lactones and nimodipine in rat plasma: Application to the pharmacokinetic study of the combination of Ginkgo biloba dispersible tablets and Nimodipine tablets.

PubMed

Xiao, Jie; Wang, Tianyang; Li, Pei; Liu, Ran; Li, Qing; Bi, Kaishun

2016-08-15

A sensitive, reliable and accurate UHPLC-MS/MS method has been firstly established and validated for the simultaneous quantification of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets and the combination of the both, respectively. The plasma samples were extracted by two step liquid-liquid extraction, nimodipine was extracted by hexane-ether (3:1, v/v) at the first step, after that ginkgo flavonoids and terpene lactones were extracted by ethyl acetate. Then the analytes were successfully separated by running gradient elution with the mobile phase consisting of 0.1% formic acid in water and methanol at a flow rate of 0.6mL/min. The detection of the analytes was performed on a UHPLC-MS/MS system with turbo ion spray source in the negative ion and multiple reaction monitoring (MRM) mode. The calibration curves for the determination of all the analytes showed good linearity (R(2)>0.99), and the lower limits of quantification were 0.50-4.00ng/mL. Intra-day and inter-day precisions were in the range of 3.6%-9.2% and 3.2%-13.1% for all the analytes. The mean extraction recoveries of the analytes were within 69.82%-103.5% and the matrix were within 82.8%-110.0%. The validated method had been successfully applied to compare the pharmacokinetic parameters of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets with the combination of the both. There were no statistically significant differences on the pharmacokinetic behaviors of all the analytes between the combined and single administration groups. Results showed that the combination of the two agents may avoid dosage adjustments in clinic and the combination is more convenient as well as efficient on different pathogenesis of cerebral ischemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

PubMed Central

Baek, Yang Hyun; Kim, Kyoung Tae; Lee, Sung Wook; Jeong, Jin Sook; Park, Byeong Ho; Nam, Kyung Jin; Cho, Jin Han; Kim, Young Hoon; Roh, Young Hoon; Lee, Hyung Sik; Choi, Young Min; Han, Sang Young

2012-01-01

AIM: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver. METHODS: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d. RESULTS: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC. CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis. PMID:22807613

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.

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

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Photodynamic Therapy of the Canine Prostate: Intra-arterial Drug Delivery

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

Moore, Ronald B.; Xiao, Zhengwen; Owen, Richard J.

2008-01-15

Purpose. Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method-intra-arterial drug delivery for PDT of the prostate-in a canine model.Methods. To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ({sup 99m}Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution.more » Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light. Results. Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of {sup 99m}Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity. Conclusion. Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.« less

Anti-stress effects of cilnidipine and nimodipine in immobilization subjected mice.

PubMed

Kumar, Naresh; Singh, Nirmal; Jaggi, Amteshwar Singh

2012-03-20

The present study was designed to investigate the ameliorative role of cilnidipine and nimodipine in immobilization stress-induced behavioral alterations and memory defects in the mice. Acute stress was induced by immobilizing the mice for 150 min and stress-induced behavioral changes were assessed using actophotometer, hole board, open field and social interaction tests. The learning and memory was evaluated using elevated plus maze tests and biochemically, the corticosterone levels were measured in the blood serum. Acute immobilization stress resulted in decrease in locomotor activity, frequency of head dips and rearings in hole board; line crossing and rearing in the open field; increase in avoidance in social behavior along with development of memory deficits assessed by an increased transfer latency time and elevation of the corticosterone levels. Administration of cilnidipine (10 mg/kg), an L and N-type dual calcium channel blocker, and nimodipine (10 mg/kg), an L-type calcium channel blocker, significantly attenuated the immobilized stress-induced behavioral changes and restored memory deficits along with normalization of the corticosterone levels. Cilnidipine and nimodipine produced comparable beneficial effects in restoring immobilization stress subjected mice. It may be concluded that cilnidipine and nimodipine mediated attenuation of corticosterone release by blockage of calcium channels (both L and N-type) on the HPA-axis is responsible for beneficial effects in restoration of behavioral alterations and memory deficits in immobilization-induced acute stress in mice. Copyright © 2011 Elsevier Inc. All rights reserved.

Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum.

PubMed

Trompette, Aurélien; Claustre, Jean; Caillon, Fabienne; Jourdan, Gérard; Chayvialle, Jean Alain; Plaisancié, Pascale

2003-11-01

Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of beta-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-casomorphin-7 (1.2 x 10(-4) mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal beta-casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, beta-endorphin (1.2 x 10(-8) to 1.2 x 10(-6) mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10(-6) mol/L), a mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.

Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice.

PubMed

Singh, Alpana; Verma, Poonam; Balaji, Gillela; Samantaray, Supriti; Mohanakumar, Kochupurackal P

2016-10-01

Parkinson's disease (PD), the most common progressive neurodegenerative movement disorder, results from loss of dopaminergic neurons of substantia nigra pars compacta. These neurons exhibit Cav1.3 channel-dependent pacemaking activity. Epidemiological studies suggest reduced risk for PD in population under long-term antihypertensive therapy with L-type calcium channel antagonists. These prompted us to investigate nimodipine, an L-type calcium channel blocker for neuroprotective effect in cellular and animal models of PD. Nimodipine (0.1-10 μM) significantly attenuated 1-methyl-4-phenyl pyridinium ion-induced loss in mitochondrial morphology, mitochondrial membrane potential and increases in intracellular calcium levels in SH-SY5Y neuroblastoma cell line as measured respectively employing Mitotracker green staining, TMRM, and Fura-2 fluorescence, but only a feeble neuroprotective effect was observed in MTT assay. Nimodipine dose-dependently reduced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian syndromes (akinesia and catalepsy) and loss in swimming ability in Balb/c mice. It attenuated MPTP-induced loss of dopaminergic tyrosine hydroxylase positive neurons in substantia nigra, improved mitochondrial oxygen consumption and inhibited reactive oxygen species production in the striatal mitochondria measured using dichlorodihydrofluorescein fluorescence, but failed to block striatal dopamine depletion. These results point to an involvement of L-type calcium channels in MPTP-induced dopaminergic neuronal death in experimental parkinsonism and more importantly provide evidences for nimodipine to improve mitochondrial integrity and function. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intra-Arterial Treatment in Patients with Acute Massive Gastrointestinal Bleeding after Endoscopic Failure: Comparisons between Positive versus Negative Contrast Extravasation Groups

PubMed Central

Chang, Wei-Chou; Liu, Chang-Hsien; Hsu, Hsian-He; Huang, Guo-Shu; Tung, Ho-Jui; Hsieh, Tsai-Yuan; Tsai, Shih-Hung; Hsieh, Chung-Bao

2011-01-01

Objective To determine whether treatment outcome is associated with visualization of contrast extravasation in patients with acute massive gastrointestinal bleeding after endoscopic failure. Materials and Methods From January 2007 to December 2009, patients that experienced a first attack of acute gastrointestinal bleeding after failure of initial endoscopy were referred to our interventional department for intra-arterial treatment. We enrolled 79 patients and divided them into two groups: positive and negative extravasation. For positive extravasation, patients were treated by coil embolization; and in negative extravasation, patients were treated with intra-arterial vasopressin infusion. The two groups were compared for clinical parameters, hemodynamics, laboratory findings, endoscopic characteristics, and mortality rates. Results Forty-eight patients had detectable contrast extravasation (positive extravasation), while 31 patients did not (negative extravasation). Fifty-six patients survived from this bleeding episode (overall clinical success rate, 71%). An elevation of hemoglobin level was observed in the both two groups; significantly greater in the positive extravasation group compared to the negative extravasation group. Although these patients were all at high risk of dying, the 90-day mortality rate was significantly lower in the positive extravasation than in the negative extravasation (20% versus 42%, p < 0.05). A multivariate analysis suggested that successful hemostasis (odds ratio [OR] = 28.66) is the most important predictor affecting the mortality in the two groups of patients. Conclusion Visualization of contrast extravasation on angiography usually can target the bleeding artery directly, resulting in a higher success rate to control of hemorrhage. PMID:21927558

Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma. Clinical article.

PubMed

Boockvar, John A; Tsiouris, Apostolos J; Hofstetter, Christoph P; Kovanlikaya, Ilhami; Fralin, Sherese; Kesavabhotla, Kartik; Seedial, Stephen M; Pannullo, Susan C; Schwartz, Theodore H; Stieg, Philip; Zimmerman, Robert D; Knopman, Jared; Scheff, Ronald J; Christos, Paul; Vallabhajosula, Shankar; Riina, Howard A

2011-03-01

The authors assessed the safety and maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of bevacizumab after osmotic disruption of the blood-brain barrier (BBB) with mannitol in patients with recurrent malignant glioma. A total of 30 patients with recurrent malignant glioma were included in the current study. The authors report no dose-limiting toxicity from a single dose of SIACI of bevacizumab up to 15 mg/kg after osmotic BBB disruption with mannitol. Two groups of patients were studied; those without prior bevacizumab exposure (naïve patients; Group I) and those who had received previous intravenous bevacizumab (exposed patients; Group II). Radiographic changes demonstrated on MR imaging were assessed at 1 month postprocedure. In Group I patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 34.7%, a median reduction in the volume of tumor enhancement of 46.9%, a median MR perfusion (MRP) reduction of 32.14%, and a T2-weighted/FLAIR signal decrease in 9 (47.4%) of 19 patients. In Group II patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 15.2%, a median volume reduction of 8.3%, a median MRP reduction of 25.5%, and a T2-weighted FLAIR decrease in 0 (0%) of 11 patients. The authors conclude that SIACI of mannitol followed by bevacizumab (up to 15 mg/kg) for recurrent malignant glioma is safe and well tolerated. Magnetic resonance imaging shows that SIACI treatment with bevacizumab can lead to reduction in tumor area, volume, perfusion, and T2-weighted/FLAIR signal.

Radiation therapy of carcinoma of the maxillary antrum (in Japanese)

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

Matsuura, S.; Taketa, C.; Ono, I.

1973-06-01

The total number of 187 cases with carcinoma of the maxillary antrum treated at National Cancer Center from 1962 to 1971 were divided into two groups. Group A (1962 to 1966) consisted of 90 cases, of which 72.2% received mainly radiotherapy with dose over 6000 rad. Group B (1967 to 1972) consisted of 97 cases, of which patients irradiated with over 6000 rad was 21.6% and intraarterial infusion of 5-FU was combined. As the injuries after irradiation, 48 cases developed radiation cataract. Advanced disturbances of visual acuity by cataract was caused by the radiation with over 4000 rad in aboutmore » two-thirds of them within 2yrs and in one third within 3to 5 yrs. In 13 patients with shielding of the eyeball from the beginning, no complications of the eyes were found except in one patient. In the injuries of the bone and the soft tissue, the fragments of the bones irradiated with high doses were easily infected and were incurable when osteomyelitis was complicated. Five cases in the over5-year survival cases showed third-degree injuries of the tissue from external irradiation with over 6000 rad. The 3-year crude survival rate of A and B group was 51.6 and 46.0% respectively, and the 5-year crude survival rate in the whole was 42.2%. Adequate combination of radiotherapy, intraarterial infusion for chemotherapy, and surgery are now under study. At present, the dose of 5-Fu was tentatively determined at 3000 mg and the radiation was 4000 rad. For the improvement of therapeutic results, programmings with plans of radiotherapy of each case and the managements of the detailed information on personal history are now under preparation as a radiotherapy using electric computer. (JA)« less

Assessment of tumoricidal efficacy and response to treatment with 18F-FDG PET/CT after intraarterial infusion with the antiglycolytic agent 3-bromopyruvate in the VX2 model of liver tumor.

PubMed

Liapi, Eleni; Geschwind, Jean-Francois H; Vali, Mustafa; Khwaja, Afsheen A; Prieto-Ventura, Veronica; Buijs, Manon; Vossen, Josephina A; Ganapathy-Kanniappan, Shanmugasudaram; Ganapathy, Shanmugasudaram; Wahl, Richard L

2011-02-01

The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with (18)F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of (18)F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUV(max)), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Intense (18)F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUV(max) was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUV(max) increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r(2) = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUV(max) on (18)F-FDG PET at 7 d after treatment with 3-BrPA. Intraarterial injection of 3-BrPA resulted in markedly decreased (18)F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA.

Assessment of Tumoricidal Efficacy and Response to Treatment with 18F-FDG PET/CT After Intraarterial Infusion with the Antiglycolytic Agent 3-Bromopyruvate in the VX2 Model of Liver Tumor

PubMed Central

Liapi, Eleni; Geschwind, Jean-Francois H.; Vali, Mustafa; Khwaja, Afsheen A.; Prieto-Ventura, Veronica; Buijs, Manon; Vossen, Josephina A.; Ganapathy, Shanmugasudaram; Wahl, Richard L.

2015-01-01

The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with 18F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Methods Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of 18F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUVmax), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Results Intense 18F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUVmax was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor–to–liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUVmax increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r2 = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUVmax on 18F-FDG PET at 7 d after treatment with 3-BrPA. Conclusion Intraarterial injection of 3-BrPA resulted in markedly decreased 18F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow antiglycolytic therapy with 3-BrPA. PMID:21233194

Orgasmic headache treated with nimodipine.

PubMed

Lee, Jea Whan; Ha, Yeon Soo; Park, Seung Chol; Seo, Ill Young; Lee, Hak Seung

2013-07-01

Orgasmic headache (OH) is a sudden and severe headache that occurs at the time of or shortly after an orgasm. AIM.: We present the case of typical primary headache associated with sexual activity, especially during an orgasmic period. A 34-year-old man complained of sudden and severe headache during sexual activity, or orgasmic period, for 2 months. The headache developed abruptly with an orgasm and then decreased shortly over a period of 4 ≈ 8 hours. Magnetic resonance angiography revealed severe spasm of the M1 segment of both the middle cerebral arteries. He was treated with oral nimodipine (30 mg every 8 hours), which alleviated the headache and prevented its recurrence. We postulated a pathophysiological relationship between OH and migraine, especially with respect to vasoconstriction, and believe that in such cases, nimodipine may be an effective therapy. © 2013 International Society for Sexual Medicine.

The effects of intrathecal nicergoline and nimodipine in cerebral vasospasm: an experimental study in rabbits.

PubMed

Solmaz, Ilker; Onal, Mehmet Bulent; Civelek, Erdinc; Kircelli, Atilla; Ongoru, Onder; Ugurel, Sahin; Erdogan, Ersin; Gonul, Engin

2011-01-01

the aim of this study was to assess and to compare the ability of intrathecal nicergoline and nimodipine in prevention of cerebral vasospasm in a rabbit model of subarachnoid hemorrhage (SAH). twenty male New Zealand white rabbits were allocated into four groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) control [no SAH (n = 5)], (2) SAH only (n = 5), (3) SAH plus nimodipine (n = 5), and (4) SAH plus nicergoline (n = 5). there was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). Basilar artery vessel diameter and luminal section areas in group 3 were significantly higher than in group 2 (p < 0.05). Basilar artery vessel diameter and basilar artery luminal section areas in group 4 were significantly higher than in group 2 (p < 0.05). There was no significant difference between basilar artery vessel diameter and basilar artery luminal section areas in group 3 and group 4. these findings demonstrate that intrathecal nicergoline has a vasodilatatory effect in an experimental model of SAH in rabbits but not more than that of nimodipine.

Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

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

Pua, Uei, E-mail: druei@yahoo.com

2013-06-15

Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192-198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960-966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

Successful Preoperative Chemoembolization in the Treatment of a Giant Malignant Phyllodes Tumor

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

Hashimoto, Kazuki, E-mail: kazkik1980@gmail.com; Mimura, Hidefumi; Arai, Yasunori

The malignant phyllodes tumor is a relatively rare neoplasm and has not previously been a therapeutic target of interventional radiology. Herein, we report a successful case of preoperative chemoembolization of a giant malignant phyllodes tumor. The objective was to achieve sufficient tumor shrinkage before surgery to avoid the requirement for skin grafting after resection. Intra-arterial epirubicin infusion and subsequent embolization with Embosphere Microspheres (BioSphere Medical, Rockland, MA, USA) was undertaken three times over the course of 6 weeks and was well tolerated. The patient underwent surgery without skin grafting. Neither local recurrence nor distant metastasis was observed at 6 months after surgery.

Endothelium-dependent vasodilatory signalling modulates α1 -adrenergic vasoconstriction in contracting skeletal muscle of humans.

PubMed

Hearon, Christopher M; Kirby, Brett S; Luckasen, Gary J; Larson, Dennis G; Dinenno, Frank A

2016-12-15

'Functional sympatholysis' describes the ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction, and is critical to ensure proper blood flow and oxygen delivery to metabolically active skeletal muscle. The signalling mechanism responsible for sympatholysis in healthy humans is unknown. Evidence from animal models has identified endothelium-derived hyperpolarization (EDH) as a potential mechanism capable of attenuating sympathetic vasoconstriction. In this study, increasing endothelium-dependent signalling during exercise significantly enhanced the ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction in humans. This is the first study in humans to identify endothelium-dependent regulation of sympathetic vasoconstriction in contracting skeletal muscle, and specifically supports a role for EDH-like vasodilatory signalling. Impaired functional sympatholysis is a common feature of cardiovascular ageing, hypertension and heart failure, and thus identifying fundamental mechanisms responsible for sympatholysis is clinically relevant. Stimulation of α-adrenoceptors elicits vasoconstriction in resting skeletal muscle that is blunted during exercise in an intensity-dependent manner. In humans, the underlying mechanisms remain unclear. We tested the hypothesis that stimulating endothelium-dependent vasodilatory signalling will enhance the ability of contracting skeletal muscle to blunt α 1 -adrenergic vasoconstriction. Changes in forearm vascular conductance (FVC; Doppler ultrasound, brachial intra-arterial pressure via catheter) to local intra-arterial infusion of phenylephrine (PE; α 1 -adrenoceptor agonist) were calculated during (1) infusion of the endothelium-dependent vasodilators acetylcholine (ACh) and adenosine triphosphate (ATP), the endothelium-independent vasodilator (sodium nitroprusside, SNP), or potassium chloride (KCl) at rest; (2) mild or moderate intensity handgrip exercise; and (3) combined mild exercise + ACh, ATP, SNP, or KCl infusions in healthy adults. Robust vasoconstriction to PE was observed during vasodilator infusion alone and mild exercise, and this was blunted during moderate intensity exercise (ΔFVC: -34 ± 4 and -34 ± 3 vs. -13 ± 2%, respectively, P < 0.05). Infusion of ACh or ATP during mild exercise significantly attenuated PE vasoconstriction similar to levels observed during moderate exercise (ACh: -3 ± 4; ATP: -18 ± 4%). In contrast, infusion of SNP or KCl during mild exercise did not attenuate PE-mediated vasoconstriction (-32 ± 5 and -46 ± 3%). To further study the role of endothelium-dependent hyperpolarization (EDH), ACh trials were repeated with combined nitric oxide synthase and cyclooxygenase inhibition. Here, PE-mediated vasoconstriction was blunted at rest (blockade: -20 ± 5 vs. -31 ± 3% vs.; P < 0.05) and remained blunted during exercise (blockade: -15 ± 5 vs. -14 ± 5%). We conclude that stimulation of EDH-like vasodilatation can blunt α 1 -adrenergic vasoconstriction in contracting skeletal muscle of humans. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Real-time monitoring of human blood-brain barrier disruption

PubMed Central

Kiviniemi, Vesa; Korhonen, Vesa; Kortelainen, Jukka; Rytky, Seppo; Keinänen, Tuija; Tuovinen, Timo; Isokangas, Matti; Sonkajärvi, Eila; Siniluoto, Topi; Nikkinen, Juha; Alahuhta, Seppo; Tervonen, Osmo; Turpeenniemi-Hujanen, Taina; Myllylä, Teemu; Kuittinen, Outi; Voipio, Juha

2017-01-01

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery. PMID:28319185

Elevated extracellular potassium prior to muscle contraction reduces onset and steady-state exercise hyperemia in humans.

PubMed

Terwoord, Janée D; Hearon, Christopher M; Luckasen, Gary J; Richards, Jennifer C; Joyner, Michael J; Dinenno, Frank A

2018-05-03

The increase in interstitial potassium (K + ) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K + in exercise hyperemia, we perfused skeletal muscle with K + prior to contractions such that the effect of any endogenously-released K + would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans. In 11 young adults, we determined forearm blood flow (FBF; Doppler ultrasound) and vascular conductance (FVC; FBF/mean arterial pressure) during 4 minutes of rhythmic handgrip exercise at 10% of maximal voluntary contraction during 1) control conditions (CTRL), 2) infusion of KCl prior to the initiation of exercise, and 3) infusion of sodium nitroprusside (SNP) as a control vasodilator. Infusion of KCl or SNP elevated resting FVC similarly prior to the onset of exercise (CTRL: 39 {plus minus} 6 vs. KCl: 81 {plus minus} 12 and SNP: 82 {plus minus} 13 ml/min/100 mmHg; both P < 0.05 vs. CTRL). Infusion of KCl at rest diminished the hyperemic (Δ FBF) and vasodilatory (Δ FVC) response to subsequent exercise by 22 {plus minus} 5% and 30 {plus minus} 5%, respectively (both P < 0.05 vs. CTRL), whereas SNP did not affect the change in FBF (P = 0.74 vs. CTRL) or FVC (P = 0.61 vs. CTRL) from rest to steady-state exercise. These findings implicate the K + ion as an essential vasodilator substance contributing to exercise hyperemia in humans.

Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.

PubMed

Ehlert, Angelika; Schmidt, Christoph; Wölfer, Johannes; Manthei, Gerd; Jacobs, Andreas H; Brüning, Roland; Heindel, Walter; Ringelstein, E Bernd; Stummer, Walter; Pluta, Ryszard M; Hesselmann, Volker

2016-01-01

OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.

SU-C-9A-05: A Medical Physics Approach to the Evaluation of a New Anti-Reflux Catheter

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

Pasciak, A; McElmurray, J

2014-06-01

Purpose: The Surefire Infusion System (SIS) is a coaxial microcatheter system with a pliant expanding tip designed to limit retrograde flow of administered intra-arterial embolic agents and resultant non-target embolization (NTE). A recent study suggests that the SIS may achieve relative arterial hypotension downstream to the catheter tip when compared to an end-hole catheter, potentially altering microsphere distribution. We have used a physics based approach to evaluate particulate distribution using both the SIS and standard end-hole microcatheter via a two-step same-day injection of Tc-99m MAA as a microsphere surrogate. Methods: Informed patient consent and IRB approval were obtained. Four patientsmore » with primary or secondary liver cancer underwent two sequential low-particulate infusions of Tc-99m MAA on the same day using both the SIS and a conventional end-hole catheter. Radiopharmaceutical dosages of approximately 1:8 were utilized in the first infusion relative to the second to eliminate the effect of residual activity on the images acquired after each step. SPECT imaging was obtained following each infusion, and MAA distribution was analyzed and compared. Archived fluoroscopic images confirmed near-identical catheter position for both infusions. Results: SPECT images from all four patients demonstrate qualitatively increased penetration of MAA distal to the site of infusion using the SIS when compared to a standard end-hole catheter. Quantitative evaluations corroborate these findings with some distal regions receiving between 33% to more than 200% greater relative activity when SIS was used. No appreciable NTE was identified in either patient subset. Conclusion: These preliminary data demonstrate the validity of this dual-infusion technique. Both qualitative and quantitative assessment of SPECT images and comparison with baseline contrast enhanced CT and PET/CT images indicate an improvement in MAA penetration into the target lesion with the SIS. However, the degree of improvement is highly dependent on tumor type and size. Financial support provided by Surefire Medical.« less

Intrathecal application of the nimodipine slow-release microparticle system eg-1962 for prevention of delayed cerebral ischemia and improvement of outcome after aneurysmal subarachnoid hemorrhage.

PubMed

Etminan, Nima; Macdonald, R Loch; Davis, Cara; Burton, Kevin; Steiger, Hans-Jakob; Hänggi, Daniel

2015-01-01

The effective reduction of delayed cerebral ischemia (DCI), a main contributor for poor outcome following aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of nicardipine pellets following surgical aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome. However, this positive effect remained restricted to patients who were treated surgically for a ruptured aneurysm. Because of the favorable results of the preclinical data on DCI and neurological outcome in the absence of neurotoxicity or systemic side effects, we are initiating clinical trials. The PROMISE (Prolonged Release nimOdipine MIcro particles after Subarachnoid hemorrhage) trial is designed as an unblinded, nonrandomized, single-center, single-dose, dose-escalation safety and tolerability phase 1 study in patients surgically treated for aSAH and will investigate the effect of intracisternal EG-1962 administration. The NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) trial is a phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation, safety, tolerability, and pharmacokinetic study comparing EG-1962 and nimodipine in patients with aneurysmal SAH.

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 inhalation are dominated by indirect effects (particle-cell interactions in the lung) rather than direct effects (translocated CNPs) within the first hours after exposure. Hence, CNP translocation may not be the key event inducing early cardiovascular impairment following air pollution episodes. The considerable response detected in the aorta after CNP inhalation warrants more emphasis on this tissue in future studies.

Histamine-induced vasodilatation in the human forearm vasculature

PubMed Central

Sandilands, Euan A; Crowe, Jane; Cuthbert, Hayley; Jenkins, Paul J; Johnston, Neil R; Eddleston, Michael; Bateman, D Nicholas; Webb, David J

2013-01-01

Aim To investigate the mechanism of action of intra-arterial histamine in the human forearm vasculature. Methods Three studies were conducted to assess changes in forearm blood flow (FBF) using venous occlusion plethysmography in response to intra-brachial histamine. First, the dose–response was investigated by assessing FBF throughout a dose-escalating histamine infusion. Next, histamine was infused at a constant dose to assess acute tolerance. Finally, a four way, double-blind, randomized, placebo-controlled crossover study was conducted to assess FBF response to histamine in the presence of H1- and H2-receptor antagonists. Flare and itch were assessed in all studies. Results Histamine caused a dose-dependent increase in FBF, greatest with the highest dose (30 nmol min−1) infused [mean (SEM) infused arm vs. control: 26.8 (5.3) vs. 2.6 ml min−1 100 ml−1; P < 0.0001]. Dose-dependent flare and itch were demonstrated. Acute tolerance was not observed, with an increased FBF persisting throughout the infusion period. H2-receptor antagonism significantly reduced FBF (mean (95% CI) difference from placebo at 30 nmol min−1 histamine: −11.9 ml min−1 100 ml−1 (−4.0, −19.8), P < 0.0001) and flare (mean (95% CI) difference from placebo: −403.7 cm2 (−231.4, 576.0), P < 0.0001). No reduction in FBF or flare was observed in response to the H1-receptor antagonist. Itch was unaffected by the treatments. Histamine did not stimulate vascular release of tissue plasminogen activator or von Willebrand factor. Conclusion Histamine causes dose-dependent vasodilatation, flare and itch in the human forearm. H2-receptors are important in this process. Our results support further exploration of combined H1- and H2-receptor antagonist therapy in acute allergic syndromes. PMID:23488545

β-Adrenergic-mediated vasodilation in young men and women: cyclooxygenase restrains nitric oxide synthase

PubMed Central

Limberg, Jacqueline K.; Johansson, Rebecca E.; Peltonen, Garrett L.; Harrell, John W.; Kellawan, J. Mikhail; Eldridge, Marlowe W.; Sebranek, Joshua J.

2016-01-01

We tested the hypothesis that women exhibit greater vasodilator responses to β-adrenoceptor stimulation compared with men. We further hypothesized women exhibit a greater contribution of nitric oxide synthase and cyclooxygenase to β-adrenergic-mediated vasodilation compared with men. Forearm blood flow (Doppler ultrasound) was measured in young men (n = 29, 26 ± 1 yr) and women (n = 33, 25 ± 1 yr) during intra-arterial infusion of isoproterenol (β-adrenergic agonist). In subset of subjects, isoproterenol responses were examined before and after local inhibition of nitric oxide synthase [NG-monomethyl-l-arginine (l-NMMA); 6 male/10 female] and/or cyclooxygenase (ketorolac; 5 male/5 female). Vascular conductance (blood flow ÷ mean arterial pressure) was calculated to assess vasodilation. Vascular conductance increased with isoproterenol infusion (P < 0.01), and this effect was not different between men and women (P = 0.41). l-NMMA infusion had no effect on isoproterenol-mediated dilation in men (P > 0.99) or women (P = 0.21). In contrast, ketorolac infusion markedly increased isoproterenol-mediated responses in both men (P < 0.01) and women (P = 0.04) and this rise was lost with subsequent l-NMMA infusion (men, P < 0.01; women, P < 0.05). β-Adrenergic vasodilation is not different between men and women and sex differences in the independent contribution of nitric oxide synthase and cyclooxygenase to β-mediated vasodilation are not present. However, these data are the first to demonstrate β-adrenoceptor activation of cyclooxygenase suppresses nitric oxide synthase signaling in human forearm microcirculation and may have important implications for neurovascular control in both health and disease. PMID:26747505

Case volumes of intra-arterial and intravenous treatment of ischemic stroke in the USA.

PubMed

Hirsch, J A; Yoo, A J; Nogueira, R G; Verduzco, L A; Schwamm, L H; Pryor, J C; Rabinov, J D; González, R G

2009-07-01

Ischemic stroke is a major cause of disability and death in the USA. Intravenous tissue plasminogen activator (t-PA) remains underutilized. With the development of newer intra-arterial reperfusion therapies, there is increased opportunity to address the more devastating large-vessel occlusions. We seek to identify the numbers of patients with stroke treated with intravenous and intra-arterial therapies, as well as to estimate the potential number of intra-arterial cases in the foreseeable future. We performed a literature search to determine case volumes of intravenous t-PA use. We extrapolated the current case volume of intra-arterial stroke therapies from the numbers of cases in which the Merci retrieval device was used. In order to estimate the potential numbers of intra-arterial stroke cases, we characterized the percentage of patients with stroke who received intra-arterial therapy at two leading stroke centers. We applied these percentages to the numbers of patients with stroke seen at the top 100, 200 and 500 stroke centers by volume. The rate of intravenous t-PA use is 2.4-3.6%, resulting in 15 000-22 000 cases/year in the USA. The estimated case volume of intra-arterial therapies is 3500-7200 in 2006. Based on data from St. Luke's Brain and Stroke Institute and Massachusetts General Hospital, approximately 5-20% of patients with ischemic stroke can be treated with intra-arterial therapies. Extrapolating this to the top 500 stroke centers by volume, the potential number of intra-arterial cases in the USA is 10 400-41 500/year. Based on the current numbers of intra-arterial cases, our theoretical model identifies a potential for significant growth of this stroke therapy.

Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral Effects.

PubMed

Cerri, Silvia; Greco, Rosaria; Levandis, Giovanna; Ghezzi, Cristina; Mangione, Antonina Stefania; Fuzzati-Armentero, Marie-Therese; Bonizzi, Arianna; Avanzini, Maria Antonietta; Maccario, Rita; Blandini, Fabio

2015-09-01

Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for Parkinson's disease (PD) and systemic administration of these cells has been tested in preclinical and clinical studies. However, no information on survival and actual capacity of MSCs to reach the brain has been provided. In this study, we evaluated homing of intraarterially infused rat MSCs (rMSCs) in the brain of rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract, to establish whether the toxin-induced damage is sufficient to grant MSC passage across the blood-brain barrier (BBB) or if a transient BBB disruption is necessary. The rMSC distribution in peripheral organs and the effects of cell infusion on neurodegenerative process and motor deficits were also investigated. rMSCs were infused 14 days after 6-OHDA injection. A hyperosmolar solution of mannitol was used to transiently permeabilize the BBB. Behavioral impairment was assessed by adjusting step test and response to apomorphine. Animals were sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable delivery of rMSCs to the brain of 6-OHDA-lesioned animals can be obtained only after mannitol pretreatment. A notable percentage of infused cells accumulated in peripheral organs. Infusion of rMSCs did not modify the progression of 6-OHDA-induced damage or the motor impairment at the stepping test, but induced progressive normalization of the pathological response (contralateral turning) to apomorphine administration. These findings suggest that many aspects should be further investigated before considering any translation of MSC systemic administration into the clinical setting for PD treatment. This study demonstrates that mesenchymal stem cells infused through the carotid artery do not efficiently cross the blood-brain barrier in rats with a Parkinson's disease-like degeneration of nigrostriatal neurons, unless a permeabilizing agent (e.g., mannitol) is used. The infusion did not reduce the neuronal damage and associated motor impairment, but abolished the motor abnormalities these animals typically show when challenged with a dopaminergic agonist. Therefore, although arterially infused mesenchymal stem cells did not show neurorestorative effects in this study's Parkinson's disease model, they appeared to normalize the pathological responsiveness of striatal neurons to dopaminergic stimulation. This capability should be further explored in future studies. ©AlphaMed Press.

Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake.

PubMed

Pitkanen, O P; Laine, H; Kemppainen, J; Eronen, E; Alanen, A; Raitakari, M; Kirvela, O; Ruotsalainen, U; Knuuti, J; Koivisto, V A; Nuutila, P

1999-12-15

1. The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be ideal to determine whether the vasoactive agent affects flow distribution or only increases the mean flow. 2. In the present study blood flow, flow distribution and glucose uptake were measured simultaneously in both legs of 10 healthy men (aged 29 +/- 1 years, body mass index 24 +/- 1 kg m-2) using positron emission tomography (PET) combined with [15O]H2O and [18F]fluoro-2-deoxy-D-glucose (FDG). The role of blood flow in muscle glucose uptake was studied by increasing blood flow in one leg with sodium nitroprusside (SNP) and measuring glucose uptake simultaneously in both legs during euglycaemic hyperinsulinaemia (insulin infusion 6 pmol kg-1 min-1). 3. SNP infusion increased skeletal muscle blood flow by 86 % (P < 0.01), but skeletal muscle flow distribution and insulin-stimulated glucose uptake (61.4 +/- 7. 5 vs. 67.0 +/- 7.5 micromol kg-1 min-1, control vs. SNP infused leg, not significant), as well as flow distribution between different tissues of the femoral region, remained unchanged. The effect of SNP infusion on blood flow and distribution were unchanged during infusion of physiological levels of insulin (duration, 150 min). 4. Despite a significant increase in mean blood flow induced by an intra-arterial infusion of SNP, glucose uptake and flow distribution remained unchanged in resting muscles of healthy subjects. These findings suggest that SNP, an endothelium-independent vasodilator, increases non-nutritive, but not nutritive flow or capillary recruitment.

Prolonged adenosine triphosphate infusion and exercise hyperemia in humans.

PubMed

Shepherd, John R A; Joyner, Michael J; Dinenno, Frank A; Curry, Timothy B; Ranadive, Sushant M

2016-09-01

In humans, intra-arterial ATP infusion in limbs mimics many features of exercise hyperemia. However, it remains unknown whether ATP can evoke the prolonged vasodilation seen during exercise. Therefore, we addressed two questions during a continuous 3-h brachial artery infusion of ATP [20 μg·100 ml forearm volume (FAV)(-1)·min(-1)]: 1) would skeletal muscle blood flow remain robust or wane over time (tachyphylaxis); and 2) would the hyperemic response to moderate-intensity exercise performed during the ATP administration be blunted compared with that during control (saline) infusion. Nine participants (25 ± 1 yr) performed one trial consisting of seven bouts of rhythmic handgrip exercise (20 contractions/min at 20% of maximum), two bouts during saline (control), and five bouts during 180 min of continuous ATP infusion. Five minutes of ATP infusion resulted in a 710% increase in forearm vascular conductance (FVC) from control (4.8 ± 0.77 vs. 35.0 ± 5.7 ml·min(-1)·100 mmHg(-1)·dl FAV(-1), P < 0.05). Contrary to our expectations, FVC did not wane over time with values of 35.0 ± 5.7 and 36.0 ± 7.7 ml·min(-1)·100 mmHg(-1)·dl FAV(-1) (P > 0.05), seen prior to the exercise bouts at 5 vs. 150 min, respectively. During superimposed exercise, FVC increased from 35.0 ± 5.7 to 49.6 ± 5.4 ml·min(-1)·100 mmHg(-1)·dl FAV(-1) at 5 min and 36.0 ± 7.7 to 54.5 ± 5.0 at 150 min (P < 0.05). Our findings demonstrate ATP vasodilation is prolonged over time without tachyphylaxis; however, exercise hyperemia responses remain intact. Our results challenge the metabolic theory of exercise hyperemia, suggesting a disconnect between matching of blood flow and metabolic demand. Copyright © 2016 the American Physiological Society.

Vasospasm After Craniopharyngioma Surgery: Can We Prevent It?

PubMed

Singh, Apinderpreeet; Salunke, Pravin; Rangan, Vasundhara; Ahuja, Chirag K; Bhadada, Sanjay

2017-05-01

Vasospasm after craniopharyngioma surgery, although rare, has been reported. Hypotheses regarding possible causative factors, including major vessel handling during surgery and tumor cyst fluid spillage, do not explain vasospasm occurring in the late postoperative period. We have attempted to consider the probable pathogenic mechanisms of this complication and measures to prevent it. Of 60 patients operated for craniopharyngiomas over a period of 4 years, 6 who had clinical and radiologically demonstrable vasospasm were identified. Each case was analyzed retrospectively, and relevant variables were studied. Five of the 6 patients developed vasospasm in the second or third week after surgery. Only 2 of these patients had a favorable outcome. There was significant altered fluid balance during this period; however, patients remained misleadingly eunatremic. This most often coincided with the transition period from syndrome of inappropriate antidiuretic hormone to diabetes insipidus (DI) and the period after steroid taper to minimal dose. Major vessel handling during radical craniopharyngioma surgery is likely to predispose them to spasm, accentuated by rapid shifts of fluid and electrolytes during different phases of DI. This is further complicated by a relative hypocortisolic state caused by tendency to taper off steroids early. Hypocortisolism masks DI leading to dehydration and possibly vasospasm. Once vasospasm develops, it is not easy to reverse. Radiologic reversal with intra-arterial nimodipine may not translate into a good clinical response. Therefore, prudence lies in its prevention. Close monitoring of fluids and electrolytes with optimal steroid cover is necessary until stabilization of DI to prevent this complication. Copyright © 2017 Elsevier Inc. All rights reserved.

The incidence of late neck recurrence in N0 maxillary sinus squamous cell carcinomas after superselective intra-arterial chemoradiotherapy without prophylactic neck irradiation.

PubMed

Sakashita, Tomohiro; Homma, Akihiro; Hatakeyama, Hiromitsu; Kano, Satoshi; Mizumachi, Takatsugu; Furusawa, Jun; Yoshida, Daisuke; Fujima, Noriyuki; Onimaru, Rikiya; Tsuchiya, Kazuhiko; Yasuda, Koichi; Shirato, Hiroki; Fukuda, Satoshi

2014-10-01

The efficacy of elective neck irradiation (ENI) for patients with N0 carcinoma of the maxillary sinus has been controversial. The purpose of our study was to investigate the incidence of late neck recurrence and the mortality rate from regional disease in patients with N0 maxillary sinus cancer after superselective cisplatin infusion and concomitant radiotherapy (RADPLAT) without ENI. We retrospectively analyzed 48 patients with N0 maxillary sinus cancer who underwent RADPLAT. Chemotherapy consisted of 100-120 mg/m(2) superselective intra-arterial cisplatin administered at a median rate of four times weekly. Concurrent radiation therapy was administered at a median dose of 65 Gy without ENI. Late neck recurrence was observed in 8.3% (4/48). Three patients underwent salvage neck dissection and survived without any evidence of disease. The remaining patient did not undergo neck dissection due to coexistence with distant metastasis, and he died of regional disease. The mortality rate from regional disease was calculated to be 2% (1/48). The incidence of late neck recurrence was not frequent, and the mortality rate from regional disease was low. Salvage neck dissection was considered to be feasible for patients with late neck recurrence. When definitive radiotherapy and concomitant chemotherapy are applied, it is considered that ENI is not required for cases of N0 maxillary sinus cancer.

Evolution of Endovascular Therapy in Acute Stroke: Implications of Device Development

PubMed Central

Balasubramaian, Adithya; Mitchell, Peter; Dowling, Richard

2015-01-01

Intravenous thrombolysis is an effective treatment for acute ischaemic stroke. However, vascular recanalization rates remain poor especially in the setting of large artery occlusion. On the other hand, endovascular intra-arterial therapy addresses this issue with superior recanalization rates compared with intravenous thrombolysis. Although previous randomized controlled studies of intra-arterial therapy failed to demonstrate superiority, the failings may be attributed to a combination of inferior intra-arterial devices and suboptimal selection criteria. The recent results of several randomized controlled trials have demonstrated significantly improved outcomes, underpinning the advantage of newer intra-arterial devices and superior recanalization rates, leading to renewed interest in establishing intra-arterial therapy as the gold standard for acute ischaemic stroke. The aim of this review is to outline the history and development of different intra-arterial devices and future directions in research. PMID:26060800

Intracranial drug delivery for subarachnoid hemorrhage.

PubMed

Macdonald, Robert Loch; Leung, Ming; Tice, Tom

2012-01-01

Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.

Influence of sodium dodecyl sulfate on swelling, erosion and release behavior of HPMC matrix tablets containing a poorly water-soluble drug.

PubMed

Zeng, Aiguo; Yuan, Bingxiang; Fu, Qiang; Wang, Changhe; Zhao, Guilan

2009-01-01

The effect of sodium dodecyl sulfate (SDS) on the swelling, erosion and release behavior of HPMC matrix tablets was examined. Swelling and erosion of HPMC matrix tablets were determined by measuring the wet and subsequent dry weights of matrices. The rate of uptake of the dissolution medium by the matrix was quantified using a square root relationship whilst the erosion of the polymer was described using the cube root law. The extent of swelling decreased with increasing SDS concentrations in the dissolution medium but the rate of erosion was found to follow a reverse trend. Such phenomena might have been caused by the attractive hydrophobic interaction between HPMC and SDS as demonstrated by the cloud points of the solutions containing both the surfactant and polymer. Release profiles of nimodipine from HPMC tablets in aqueous media containing different concentrations of SDS were finally studied. Increasing SDS concentrations in the medium was shown to accelerate the release of nimodipine from the tablets, possibly due to increasing nimodipine solubility and increasing rate of erosion by increasing SDS concentrations in the dissolution medium.

Angiographic evaluation and management of acute gastrointestinal hemorrhage

PubMed Central

Walker, T Gregory; Salazar, Gloria M; Waltman, Arthur C

2012-01-01

Although most cases of acute nonvariceal gastrointestinal hemorrhage either spontaneously resolve or respond to medical management or endoscopic treatment, there are still a significant number of patients who require emergency angiography and transcatheter treatment. Evaluation with noninvasive imaging such as nuclear scintigraphy or computed tomography may localize the bleeding source and/or confirm active hemorrhage prior to angiography. Any angiographic evaluation should begin with selective catheterization of the artery supplying the most likely site of bleeding, as determined by the available clinical, endoscopic and imaging data. If a hemorrhage source is identified, superselective catheterization followed by transcatheter microcoil embolization is usually the most effective means of successfully controlling hemorrhage while minimizing potential complications. This is now well-recognized as a viable and safe alternative to emergency surgery. In selected situations transcatheter intra-arterial infusion of vasopressin may also be useful in controlling acute gastrointestinal bleeding. One must be aware of the various side effects and potential complications associated with this treatment, however, and recognize the high re-bleeding rate. In this article we review the current role of angiography, transcatheter arterial embolization and infusion therapy in the evaluation and management of nonvariceal gastrointestinal hemorrhage. PMID:22468082

Overexpression of VLA-4 in glial-restricted precursors enhances their endothelial docking and induces diapedesis in a mouse stroke model.

PubMed

Jablonska, Anna; Shea, Daniel J; Cao, Suyi; Bulte, Jeff Wm; Janowski, Miroslaw; Konstantopoulos, Konstantinos; Walczak, Piotr

2018-05-01

The loss of oligodendrocytes after stroke is one of the major causes of secondary injury. Glial-restricted progenitors (GRPs) have remylenating potential after intraparenchymal cerebral transplantation. The intraarterial (IA) injection route is an attractive gateway for global brain delivery, but, after IA infusion, naive GRPs fail to bind to the cerebral vasculature. The aim of this study was to test whether overexpression of Very Late Antigen-4 (VLA-4) increases endothelial docking and cerebral homing of GRPs in a stroke model. Mouse GRPs were co-transfected with DNA plasmids encoding VLA-4 subunits (α4, β1). The adhesion capacity and migration were assessed using a microfluidic assay. In vivo imaging of the docking and homing of IA-infused cells was performed using two-photon microscopy in a mouse middle cerebral artery occlusion (MCAO) model. Compared to naïve GRPs, transfection of GRPs with VLA-4 resulted in >60% higher adhesion (p < 0.05) to both purified Vascular Cell Adhesion Molecule-11 (VCAM-11) and TNFα-induced endothelial VCAM-1. VLA-4 + GRPs displayed a higher migration in response to a chemoattractant gradient. Following IA infusion, VLA-4 + GRPs adhered to the vasculature at three-fold greater numbers than naïve GRPs. Multi-photon imaging confirmed that VLA-4 overexpression increases the efficiency of GRP docking and leads to diapedesis after IA transplantation. This strategy may be further exploited to increase the efficacy of cellular therapeutics.

Impaired modulation of postjunctional α1 - but not α2 -adrenergic vasoconstriction in contracting forearm muscle of postmenopausal women.

PubMed

Kruse, Nicholas T; Hughes, William E; Ueda, Kenichi; Hanada, Satoshi; Feider, Andrew J; Iwamoto, Erika; Bock, Joshua M; Casey, Darren P

2018-04-30

Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in skeletal muscle of ageing males, brought on by altered postjunctional α 1 - and α 2 -adrenergic receptor sensitivity. The extent to which postjunctional α-adrenergic vasoconstriction occurs in the forearms at rest and during exercise in postmenopausal women remains unknown. The novel findings indicate that contraction-mediated blunting of α 1 - (via intra-arterial infusion of phenylephrine) but not α 2 -adrenergic (via intra-arterial infusion of dexmedetomidine) vasoconstriction was attenuated in postmenopausal women compared to young women. Additional important findings revealed that postjunctional α-adrenergic vasoconstrictor responsiveness at rest does not appear to be affected by age in women. Collectively, these results contribute to our understanding of local neurovascular control at rest and during exercise with age in women. Contraction-mediated blunting of postjunctional α-adrenergic vasoconstriction (functional sympatholysis) is attenuated in older males; however, direct confirmation of this effect remains unknown in postmenopausal women (PMW). The present study examined whether PMW exhibit augmented postjunctional α-adrenergic receptor vasoconstriction at rest and during forearm exercise compared to young women (YW). Eight YW (24 ± 1 years) and eight PMW (65 ± 1 years) completed a series of randomized experimental trials: (1) at rest, (2) under high flow (adenosine infusion) conditions and (3) during 6 min of forearm exercise at relative (20% of maximum) and absolute (7 kg) intensities. Phenylephrine (α 1 -agonist) or dexmedetomidine (α 2 -agonist) was administered during the last 3 min of each trial to elicit α-adrenergic vasoconstriction. Forearm vascular conductance (FVC) was calculated from blood flow and blood pressure. Vasoconstrictor responsiveness was identified as the change in FVC (%) during α-adrenergic agonist infusions from baseline (resting trial) or from steady-state conditions (high flow and exercise trials). During resting and high flow trials, the %FVC during α 1 - and α 2 -agonist stimulation was similar between YW and PMW. During exercise, α 1 -mediated vasoconstriction was blunted in YW vs. PMW at relative (-6 ± 2% vs. -15 ± 3%) and absolute (-4 ± 2% vs. -14 ± 5%) workloads, such that blood flow and FVC were lower in PMW (P < 0.05 for all). Conversely, α 2 -mediated vasoconstriction was similar between YW and PMW at relative (-22 ± 3% vs. -22 ± 4%; P > 0.05) and absolute (-19 ± 3% vs. -18 ± 4%; P > 0.05) workloads. Collectively, these findings demonstrate that despite similar α-adrenergic vasoconstrictor responsiveness at rest, PMW have a decreased ability to attenuate α 1 -adrenergic vasoconstriction in contracting skeletal muscle. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

A Novel External Carotid Arterial Sheath System for Intra-arterial Infusion Chemotherapy of Head and Neck Cancer.

PubMed

Ii, Noriko; Fuwa, Nobukazu; Toyomasu, Yutaka; Takada, Akinori; Nomura, Miwako; Kawamura, Tomoko; Sakuma, Hajime; Nomoto, Yoshihito

2017-07-01

The purpose of this study was to describe a novel system for treating advanced head and neck cancer consisting of an external carotid arterial sheath (ECAS) and a microcatheter to inject drugs retrogradely into multiple feeding arteries through the superficial temporal artery (STA). Four consecutive patients with head and neck cancer that had more than one feeding artery were enrolled in this study. The ECAS was made of polyurethane and surface-coated with heparin resin to prevent thrombus formation, allowing it to remain in place for a prolonged period of time. The ECAS was inserted through the STA, and its tip was placed between the maxillary artery and facial artery. The tumor-feeding arteries were selected using a hooked-shaped microcatheter through the ECAS. A total of 13 target arteries were selected in the four patients. The microcatheter inserted via the ECAS was used to catheterize ten arteries (five lingual arteries and five facial arteries). The remaining three lingual arteries were directly selected by the catheter without ECAS. All of the target arteries were able to be catheterized superselectively. The technical success rate was 100%. Vascular occlusion, which might have been caused by the ECAS, was observed in one patient. No neurologic toxicities occurred. This ECAS system is a new approach for retrograde superselective intra-arterial chemotherapy that covers the entire tumor with anticancer drugs. It has the potential to increase the effectiveness of therapy for advanced head and neck cancer. Level 4, Case Series.

Importance of technical preparation of intraarterial shunts to prevent iatrogenic arterial injury during urgent procedures.

PubMed

Awad, Nadia; Choudry, Rashad; Durinka, Joel; Prabhu, Aparna; Dissin, Jonathan

2013-02-01

Although intraarterial shunting during carotid endarterectomy is a well-defined practice, its use remains controversial. Complication rates associated with shunt placement remain low, but may be underreported. When complications secondary to routine intraarterial shunting occur, they can cause significant morbidity or even mortality, emphasizing the importance of meticulous technique to prevent adverse outcomes. We report a case of internal carotid artery dissection and pseuedoaneurysm due to the technical failure of a safety device of an intraarterial shunt used during carotid endarterectomy.

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

Roy, Sumit; Laerum, Frode; Brosstad, Frank

Purpose: To develop an animal model of acute deep vein thrombosis (DVT). Methods: In part I of the study nine juvenile domestic pigs were used. Each external iliac vein was transluminally occluded with a balloon catheter. Thrombin was infused through a microcatheter in one leg according to one of the following protocols: (1) intraarterial (IA): 1250 U at 25 U/min in the common femoral artery (n= 3); (2) intravenous (IV): 5000 U in the popliteal vein at 500 U/min (n= 3), or at 100 U/min (n= 3). Saline was administered in the opposite leg. After the animals were killed, themore » mass of thrombus in the iliofemoral veins was measured. The pudendoepiploic (PEV), profunda femoris (PF), and popliteal veins (PV) were examined. Thrombosis in the tributaries of the superficial femoral vein (SFVt) was graded according to a three-point scale (0, +, ++). In part II of the study IV administration was further investigated in nine pigs using the following three regimens with 1000 U at 25 U/min serving as the control: (1) 1000 U at 100 U/min, (2) 250 U at 25 U/min, (3) 250 U at 6.25 U/min. Results: All animals survived. In part I median thrombus mass in the test limbs was 1.40 g as compared with 0.25 g in the controls (p= 0.01). PEV, PFV and PV were thrombosed in all limbs infused with thrombin. IV infusion was more effective in inducing thrombosis in both the parent veins (mass 1.32-1.78 g) and SVFt (++ in 4 of 6 legs), as compared with IA infusion (mass 0.0-1.16 g; SFVt ++ in 1 of 3 legs). In part II thrombus mass in axial veins ranged from 1.23 to 2.86 g, and showed no relationship with the dose of thrombin or the rate of infusion. Tributary thrombosis was less extensive with 250 U at 25 U/min than with the other regimens. Conclusion: Slow distal intravenous thrombin infusion in the hind legs of pigs combined with proximal venous occlusion induces thrombosis in the leg veins that closely resembles clinical DVT in distribution.« less

New daily persistent headache with a thunderclap headache onset and complete response to nimodipine (a new distinct subtype of NDPH).

PubMed

Rozen, Todd D; Beams, Jennifer L

2013-12-23

At present new daily persistent headache is just a group of conditions that are connected based on the temporal profile of their mode of onset. If new daily persistent headache is a true distinct syndrome like migraine then we need to start to define subtypes that have specific effective treatments such has been noted for migraine sub-forms. We present what we believe is the first recognized subtype of new daily persistent headache that which starts with a thunderclap headache onset. A patient presented with a 13 month history of a daily headache from onset which initiated as a thunderclap headache along with persistent acalculia. All neuroimaging studies for secondary causes were negative. Nimodipine rapidly and completely alleviated her headache and associated neurologic symptoms. We propose that this subtype of new daily persistent headache is caused by a very rapid increase in CSF tumor necrosis factor alpha levels leading to cerebral artery vasospasm with a subsequent thunderclap headache, then continuous or near continuous cerebral artery vasospasm leading to a persistent daily headache. Nimodipine which not only inhibits cerebral artery vasospasm but also tumor necrosis factor alpha production appears to be a specific treatment for this distinct subtype of new daily persistent headache.

New daily persistent headache with a thunderclap headache onset and complete response to Nimodipine (A new distinct subtype of NDPH)

PubMed Central

2013-01-01

At present new daily persistent headache is just a group of conditions that are connected based on the temporal profile of their mode of onset. If new daily persistent headache is a true distinct syndrome like migraine then we need to start to define subtypes that have specific effective treatments such has been noted for migraine sub-forms. We present what we believe is the first recognized subtype of new daily persistent headache that which starts with a thunderclap headache onset. A patient presented with a 13 month history of a daily headache from onset which initiated as a thunderclap headache along with persistent acalculia. All neuroimaging studies for secondary causes were negative. Nimodipine rapidly and completely alleviated her headache and associated neurologic symptoms. We propose that this subtype of new daily persistent headache is caused by a very rapid increase in CSF tumor necrosis factor alpha levels leading to cerebral artery vasospasm with a subsequent thunderclap headache, then continuous or near continuous cerebral artery vasospasm leading to a persistent daily headache. Nimodipine which not only inhibits cerebral artery vasospasm but also tumor necrosis factor alpha production appears to be a specific treatment for this distinct subtype of new daily persistent headache. PMID:24364890

Prospective correlative chemosensitivity testing in high-dose intraarterial chemotherapy for liver metastases.

PubMed

Link, K H; Aigner, K R; Kuehn, W; Schwemmle, K; Kern, D H

1986-09-01

Clinical response of liver metastases treated by high-dose intraarterial chemotherapy (HDIAC) delivered via the hepatic artery was predicted by a modification of the human tumor colony-forming assay (HTCFA) originally described by Hamburger and Salmon [Science (Wash. DC), 197:461-463, 1977. In a first set of experiments, the immediate clinical response to HDIAC was determined in 12 patients with colorectal liver metastases. Biopsies were taken immediately before and after HDIAC, and cells were plated in the HTCFA. Three patients received intraoperative 4-epidoxorubicin and another 9 received mitomycin C by 15-min intraarterial infusions. Sensitivity in the HTCFA was defined as 50% inhibition of colony formation in tumors exposed to the chemotherapeutic agent, compared to the untreated controls. Clinical response was accurately predicted by the HTCFA in 11 of 12 cases. Eight patients had a regression of disease following HDIAC treatment with mitomycin C, as evidenced by either greater than 50% reduction in carcinoembryonic antigen serum level (7 patients) or regression of tumor by computed tomography scan (1 patient). Three patients had no evidence of clinical response to epidoxorubicin, and their tumors were resistant to epidoxorubicin in the HTCFA. One tumor was sensitive to mitomycin C in the HTCFA, but serum carcinoembryonic antigen in the patient continued to increase following HDIAC. The HTCFA was also performed on untreated biopsies following incubation in vitro with the drug used for HDIAC. Results correlated with clinical response in all 12 cases. In a second set of experiments, the HTCFA was used to predict the long-term clinical response to HDIAC of 30 patients with liver metastases. One patient had breast cancer metastases, one patient had carcinoid liver metastases, 4 had liver metastases of malignant melanoma, and 24 patients had colorectal liver metastases. All 21 of the patients whose tumors were sensitive in vitro had clinical response, while 6 of 9 patients predicted by the HTCFA to be resistant had no clinical response. Our results demonstrate a high correlation between the HTCFA and clinical response.

Retrobulbar ocular blood flow changes measured by colour Doppler imaging after intra-arterial chemotherapy in retinoblastoma.

PubMed

Xue, Kang; Liu, Ailin; Hui, Ren; Zhang, Jing; Qian, Jiang

2017-10-01

To evaluate the effects of intra-arterial chemotherapy on retrobulbar blood flow parameters in patients with retinoblastoma. 20 eyes of 10 patients with unilateral retinoblastoma that were treated with intra-arterial chemotherapy were evaluated using colour Doppler imaging. The peak systolic and end-diastolic velocities of the ophthalmic, central retinal and posterior ciliary arteries were determined. The pulsatility and resistance indices were calculated automatically. The treated eye was compared with the untreated (control) eye and with itself before and after intra-arterial chemotherapy. When comparing the retinoblastoma-containing eyes with the contralateral normal eyes, the peak systolic and end-diastolic velocities of the central retinal artery were significantly higher in the tumorous eyes than in the normal eyes before intra-arterial chemotherapy. Moreover, the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries were significantly decreased after intra-arterial chemotherapy in the tumorous eyes (p<0.05). There were no statistically significant differences in the other parameters. Our results suggest that intra-arterial chemotherapy has a measurable effect on the retrobulbar blood flow, which can cause a decrease in the peak systolic and end-diastolic velocities in the posterior ciliary and central retinal arteries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Interventional radiology procedures for malignancies of the liver treatment: Intraarterial procedures].

PubMed

Cristina, V; Pracht, M; Lachenal, Y; Adib, S; Boubaker, A; Prior, J; Senys, A; Wagner, A D; Bize, P

2014-05-21

Intraarterial procedures such as chemoembolization and radioembolization aim for the palliative treatment of advanced hepatocellular carcinoma (stage BCLC B and C with tumoral portal thrombosis). The combination of hepatic intraarterial chemotherapy and systemic chemotherapy can increase the probability of curing colorectal cancer with hepatic metastases not immediately accessible to surgical treatment or percutaneous ablation.

Reconsolidation Allows Fear Memory to Be Updated to a Less Aversive Level through the Incorporation of Appetitive Information

PubMed Central

Haubrich, Josue; Crestani, Ana P; Cassini, Lindsey F; Santana, Fabiana; Sierra, Rodrigo O; Alvares, Lucas de O; Quillfeldt, Jorge A

2015-01-01

The capacity to adapt to new situations is one of the most important features of memory. When retrieved, memories may undergo a labile state that is sensitive to modification. This process, called reconsolidation, can lead to memory updating through the integration of new information into a previously consolidated memory background. Thus reconsolidation provides the opportunity to modify an undesired fear memory by updating its emotional valence to a less aversive level. Here we evaluated whether a fear memory can be reinterpreted by the concomitant presentation of an appetitive stimulus during its reactivation, hindering fear expression. We found that memory reactivation in the presence of appetitive stimuli resulted in the suppression of a fear response. In addition, fear expression was not amenable to reinstatement, spontaneous recovery, or rapid reacquisition. Such effect was prevented by either systemic injection of nimodipine or intra-hippocampal infusion of ifenprodil, indicating that memory updating was mediated by a reconsolidation mechanism relying on hippocampal neuronal plasticity. Taken together, this study shows that reconsolidation allows for a ‘re-signification' of unwanted fear memories through the incorporation of appetitive information. It brings a new promising cognitive approach to treat fear-related disorders. PMID:25027331

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

PubMed Central

Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

2017-01-01

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors.

PubMed

Tosi, Umberto; Marnell, Christopher S; Chang, Raymond; Cho, William C; Ting, Richard; Maachani, Uday B; Souweidane, Mark M

2017-02-08

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Nimodipine

MedlinePlus

... caused by a subarachnoid hemorrhage (bleeding in the space surrounding the brain that occurs when a weakened ... you should not flush this medication down the toilet. Instead, the best way to dispose of your ...

Determination of nitrosourea compounds in brain tissue by gas chromatography and electron capture detection.

PubMed

Hassenbusch, S J; Colvin, O M; Anderson, J H

1995-07-01

A relatively simple, high-sensitivity gas chromatographic assay is described for nitrosourea compounds, such as BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and MeCCNU [1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea], in small biopsy samples of brain and other tissues. After extraction with ethyl acetate, secondary amines in BCNU and MeCCNU are derivatized with trifluoroacetic anhydride. Compounds are separated and quantitated by gas chromatography using a capillary column with temperature programming and an electron capture detector. Standard curves of BCNU indicate a coefficient of variance of 0.066 +/- 0.018, a correlation coefficient of 0.929, and an extraction efficiency from whole brain of 68% with a minimum detectable amount of 20 ng in 5-10 mg samples. The assay has been facile and sensitive in over 1000 brain biopsy specimens after intravenous and intraarterial infusions of BCNU.

A randomized trial of intraarterial treatment for acute ischemic stroke.

PubMed

Berkhemer, Olvert A; Fransen, Puck S S; Beumer, Debbie; van den Berg, Lucie A; Lingsma, Hester F; Yoo, Albert J; Schonewille, Wouter J; Vos, Jan Albert; Nederkoorn, Paul J; Wermer, Marieke J H; van Walderveen, Marianne A A; Staals, Julie; Hofmeijer, Jeannette; van Oostayen, Jacques A; Lycklama à Nijeholt, Geert J; Boiten, Jelis; Brouwer, Patrick A; Emmer, Bart J; de Bruijn, Sebastiaan F; van Dijk, Lukas C; Kappelle, L Jaap; Lo, Rob H; van Dijk, Ewoud J; de Vries, Joost; de Kort, Paul L M; van Rooij, Willem Jan J; van den Berg, Jan S P; van Hasselt, Boudewijn A A M; Aerden, Leo A M; Dallinga, René J; Visser, Marieke C; Bot, Joseph C J; Vroomen, Patrick C; Eshghi, Omid; Schreuder, Tobien H C M L; Heijboer, Roel J J; Keizer, Koos; Tielbeek, Alexander V; den Hertog, Heleen M; Gerrits, Dick G; van den Berg-Vos, Renske M; Karas, Giorgos B; Steyerberg, Ewout W; Flach, H Zwenneke; Marquering, Henk A; Sprengers, Marieke E S; Jenniskens, Sjoerd F M; Beenen, Ludo F M; van den Berg, René; Koudstaal, Peter J; van Zwam, Wim H; Roos, Yvo B W E M; van der Lugt, Aad; van Oostenbrugge, Robert J; Majoie, Charles B L M; Dippel, Diederik W J

2015-01-01

In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

Flow dependence of forearm noradrenaline overflow, as assessed during mental stress and sodium nitroprusside infusion.

PubMed

Lindqvist, M; Melcher, A; Hjemdahl, P

1999-01-01

To evaluate the influence of blood flow on measurements of regional sympathetic nerve activity by radiotracer methodology ([3H]noradrenaline). Ten healthy men were studied under two conditions of elevated forearm blood flow: mental stress (Stroop colour word conflict test) and an intra-arterial infusion of sodium nitroprusside. Arterial blood pressure was measured invasively and forearm blood flow with strain-gauge plethysmography. Arterial and venous plasma adrenaline and noradrenaline were measured with high-performance liquid chromatography, and regional and total noradrenaline spillover were calculated. During mental stress, mean arterial pressure increased by 17%, heart rate by 16 beats/min, forearm blood flow by 117%, while forearm vascular resistance decreased by 44% (P < 0.001 for all). Sodium nitroprusside increased forearm blood flow dose-dependently, but elicited only minor effects on systemic haemodynamics. Mental stress increased arterial plasma noradrenaline by 52% (P < 0.001), and total body noradrenaline spillover by 75% (P < 0.001). During sodium nitroprusside infusion, arterial plasma noradrenaline increased only slightly and total body noradrenaline spillover was unaffected Forearm noradrenaline overflow increased from 5.4 +/- 0.9 to 16.9 +/- 2.6 pmol/min per I (P < 0.001) during mental stress and from 6.6 +/- 0.8 to 16.9 +/- 3.7 pmol/min per I (P < 0.001) during the second dose-step of sodium nitroprusside infusion. By intra-individual comparisons of forearm noradrenaline overflow increases during mental stress and during sodium nitroprusside infusion, with similar forearm blood flow increases, the flow dependence of forearm noradrenaline overflow was estimated. During mental stress, about 60% (median value, range 29-112%) of the increase in forearm noradrenaline overflow was attributed to the increase in forearm blood flow, whereas 40% was considered to reflect increased sympathetic nerve activity. There seems to be a considerable flow dependence of the regional overflow of noradrenaline, that is, a component of simple wash-out of noradrenaline from the forearm tissues during vasodilation. However, the present results still indicate that sympathetic nerve activity in the forearm is increased during mental stress, justifying the radiotracer technique for semiquantitative measurements, also during vasodilation.

Correlation of Noninvasive Blood Pressure and Invasive Intra-arterial Blood Pressure in Patients Treated with Vasoactive Medications in a Neurocritical Care Unit.

PubMed

Saherwala, Ali A; Stutzman, Sonja E; Osman, Mohamed; Kalia, Junaid; Figueroa, Stephen A; Olson, DaiWai M; Aiyagari, Venkatesh

2018-03-22

The correlation between noninvasive (oscillometric) blood pressure (NBP) and intra-arterial blood pressure (IAP) in critically ill patients receiving vasoactive medications in a Neurocritical Care Unit has not been systematically studied. The purpose of this study is to examine the relationship between simultaneously measured NBP and IAP recordings in these patients. Prospective observational study of patients (N = 70) admitted to a neurocritical care unit receiving continuous vasopressor or antihypertensive infusions. Paired NBP/IAP observations along with covariate and demographic data were abstracted via chart audit. Analysis was performed using SAS v9.4. A total of 2177 paired NBP/IAP observations from 70 subjects (49% male, 63% white, mean age 59 years) receiving vasopressors (n = 21) or antihypertensive agents (n = 49) were collected. Paired t test analysis showed significant differences between NBP versus IAP readings: ([systolic blood pressure (SBP): mean = 136 vs. 140 mmHg; p < 0.0001], [diastolic blood pressure (DBP): mean = 70 vs. 68 mmHg, p < 0.0001], [mean arterial blood pressure (MAP): mean = 86 vs. 90 mmHg, p < 0.0001]). Bland-Altman plots for MAP, SBP, and DBP demonstrate good inter-method agreement between paired measures (excluding outliers) and demonstrate NBP-IAP SBP differences at extremes of blood pressures. Pearson correlation coefficients show strong positive correlations for paired MAP (r = 0.82), SBP (r = 0.84), and DBP (r = 0.73) recordings. An absolute NBP-IAP SBP difference of > 20 mmHg was seen in ~ 20% of observations of nicardipine, ~ 25% of observations of norepinephrine, and ~ 35% of observations of phenylephrine. For MAP, the corresponding numbers were ~ 10, 15, and 25% for nicardipine, norepinephrine, and phenylephrine, respectively. Despite overall strong positive correlations between paired NBP and IAP readings of MAP and SBP, clinically relevant differences in blood pressure are frequent. When treating with vasoactive infusions targeted to a specific BP goal, it is important to keep in mind that NBP and IAP values are not interchangeable.

Sildenafil Increases Sympathetically Mediated Vascular Tone in Humans

PubMed Central

2013-01-01

BACKGROUND Sildenafil, a selective phosphodiesterase-type-5 (PDE-5) inhibitor, produces vasodilation that improves erectile dysfunction and pulmonary hypertension. Sildenafil could also cause baroreflex sympathetic activation that would enhance vascular tone and oppose direct vasodilation. We tested the hypothesis that sildenafil administration increases sympathetically mediated vascular tone in healthy middle-aged men. METHODS We randomized 9 healthy, middle-aged, male volunteers (mean age 45±2 years) in a double-blind, crossover fashion to receive a single oral dose of sildenafil 100mg or placebo on 2 separate study days. Hemodynamics and forearm blood flow responses were measured at baseline, at 30 and 45 minutes after study drug administration, and then during intra-arterial infusions of vasoactive drugs. After sildenafil and placebo administration, intrabrachial medications were infused to test forearm alpha receptor sensitivity (norepinephrine), cyclic-AMP–mediated vasodilation (isoproterenol), and sympathetically mediated vascular tone (phentolamine) (adenosine was a control vasodilator). Blood samples were taken before and 60 minutes after study drug administration and at the end of the intrabrachial infusions for measurement of plasma norepinephrine concentrations. RESULTS Forearm vascular responses to norepinephrine, isoproterenol, and adenosine were not different after placebo and sildenafil administration. Percentage reduction in forearm vascular resistance during phentolamine was significantly lower after sildenafil than placebo (−73% ± 3% vs −63% ± 3%; P = 0.0002). Sildenafil significantly increased plasma norepinephrine compared with placebo 60 minutes after study drug administration and at the end of the study session (P = 0.02). CONCLUSIONS Sildenafil increased sympathetically mediated vascular tone in middle-aged healthy men. Alpha-adrenergic–mediated vasoconstriction may offset vasodilation during PDE-5 inhibition and may explain the significant hypotension observed in patients taking alpha-blockers with sildenafil. PMID:23443723

Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function

PubMed Central

Kanias, Tamir; Triulzi, Darrel; Donadee, Chenell; Barge, Suchitra; Badlam, Jessica; Jain, Shilpa; Belanger, Andrea M.; Kim-Shapiro, Daniel B.

2015-01-01

Rationale: A major abnormality that characterizes the red cell “storage lesion” is increased hemolysis and reduced red cell lifespan after infusion. Low levels of intravascular hemolysis after transfusion of aged stored red cells disrupt nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell-free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion and effects on endothelial-dependent vasodilation responses to acetylcholine have not been fully characterized in humans. Objectives: To evaluate the effects of blood aged to the limits of Food and Drug Administration–approved storage time on the human microcirculation and endothelial function. Methods: Eighteen healthy individuals donated 1 U of leukopheresed red cells, divided and autologously transfused into the forearm brachial artery 5 and 42 days after blood donation. Blood samples were obtained from stored blood bag supernatants and the antecubital vein of the infusion arm. Forearm blood flow measurements were performed using strain-gauge plethysmography during transfusion, followed by testing of endothelium-dependent blood flow with increasing doses of intraarterial acetylcholine. Measurements and Main Results: We demonstrate that aged stored blood has higher levels of arginase-1 and cell-free plasma hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells decreases acetylcholine-dependent forearm blood flows. Intravascular venous levels of arginase-1 and cell-free plasma hemoglobin increase immediately after red cell transfusion, with more significant increases observed after infusion of 42-day-old blood. Conclusions: We demonstrate that the transfusion of blood at the limits of Food and Drug Administration–approved storage has a significant effect on the forearm circulation and impairs endothelial function. Clinical trial registered with www.clinicaltrials.gov (NCT 01137656) PMID:26222884

The role of α-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man

PubMed Central

Fairfax, Seth T; Holwerda, Seth W; Credeur, Daniel P; Zuidema, Mozow Y; Medley, John H; Dyke II, Peter C; Wray, D Walter; Davis, Michael J; Fadel, Paul J

2013-01-01

Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra-arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P= 0.016) and then robustly decreased to a nadir of −5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (–2.1 ± 0.7% and –0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors. PMID:23652594

Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment.

PubMed

Gornicka-Pawlak, El Bieta; Janowski, Miroslaw; Habich, Aleksandra; Jablonska, Anna; Drela, Katarzyna; Kozlowska, Hanna; Lukomska, Barbara; Sypecka, Joanna; Domanska-Janik, Krystyna

2011-01-01

The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.

Dissociation between neural and vascular responses to sympathetic stimulation : contribution of local adrenergic receptor function

NASA Technical Reports Server (NTRS)

Jacob, G.; Costa, F.; Shannon, J.; Robertson, D.; Biaggioni, I.

2000-01-01

Sympathetic activation produced by various stimuli, eg, mental stress or handgrip, evokes regional vascular responses that are often nonhomogeneous. This phenomenon is believed to be the consequence of the recruitment of differential central neural pathways or of a sympathetically mediated vasodilation. The purpose of this study was to determine whether a similar heterogeneous response occurs with cold pressor stimulation and to test the hypothesis that local differences in adrenergic receptor function could be in part responsible for this diversity. In 8 healthy subjects, local norepinephrine spillover and blood flow were measured in arms and legs at baseline and during sympathetic stimulation induced by baroreflex mechanisms (nitroprusside infusion) or cold pressor stimulation. At baseline, legs had higher vascular resistance (27+/-5 versus 17+/-2 U, P=0.05) despite lower norepinephrine spillover (0.28+/-0.04 versus 0.4+/-0.05 mg. min(-1). dL(-1), P=0.03). Norepinephrine spillover increased similarly in both arms and legs during nitroprusside infusion and cold pressor stimulation. On the other hand, during cold stimulation, vascular resistance increased in arms but not in legs (20+/-9% versus -7+/-4%, P=0.03). Increasing doses of isoproterenol and phenylephrine were infused intra-arterially in arms and legs to estimate beta-mediated vasodilation and alpha-induced vasoconstriction, respectively. beta-Mediated vasodilation was significantly lower in legs compared with arms. Thus, we report a dissociation between norepinephrine spillover and vascular responses to cold stress in lower limbs characterized by a paradoxical decrease in local resistance despite increases in sympathetic activity. The differences observed in adrenergic receptor responses cannot explain this phenomenon.

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

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

Mendez, Jose C.; Masjuan, J.; Garcia, N.

2008-01-15

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

Intra-arterial Stroke Management

PubMed Central

Prince, Ethan A.; Ahn, Sun Ho; Soares, Gregory M.

2013-01-01

Acute ischemic stroke is a leading cause of death and the leading cause of disability in the United States. Cerebral neuronal death begins within minutes after threshold values of blood oxygen saturation are crossed. Prompt restoration of oxygenated blood flow into ischemic tissue remains the common goal of reperfusion strategies. This article provides a brief overview of acute ischemic stroke, a summary of the major intra-arterial stroke therapy trials, and comments on current training requirements for the performance of intra-arterial therapies. PMID:24436550

Unresectable liver metastases in colorectal cancer: review of current strategies.

PubMed

Sueur, Benjamin; Pellerin, Olivier; Voron, Thibault; Pointet, Anne L; Taieb, Julien; Pernot, Simon

2016-12-01

The objective of the treatment of colorectal cancer patients with unresectable liver metastases should be clearly defined at the outset. Potentially resectable patients should be distinguished from clearly unresectable patients. In defining resectability, it is important to take into account both anatomic characteristics and patient characteristic (comorbidities, symptoms, age). According to this evaluation, treatment should be tailored to each patient. The most widely accepted standard is doublet cytotoxic regimen plus biotherapy (anti-EGFR or anti-VEGF antibodies according to RAS status, but some patients could benefit from an intensified regimen, as triplet chemotherapy ± bevacizumab, or intraarterial treatments (hepatic arterial infusion, radioembolization or chemoembolization), in order to allow resectability. It is therefore very important to discuss the treatments with a multidisciplinary team, including an experienced surgeon, an interventional radiologist and an oncologist. On the other hand, some patients could benefit in terms of quality of life and decreased toxicity from less intense treatment when resection is not an objective. First-line monotherapy or a maintenance strategy with biotherapy and/or cytotoxics could be discussed with these patients, and treatment holidays should be considered in selected patients. Finally, in patients with secondary resection of liver metastases, specificity should be considered in choosing the best adjuvant treatment, such as response to preoperative treatment and individual risk of relapse, which many in some cases justify intensification with hepatic arterial infusion in an adjuvant setting.

Memory reconsolidation may be disrupted by a distractor stimulus presented during reactivation

PubMed Central

Crestani, Ana Paula; Zacouteguy Boos, Flávia; Haubrich, Josué; Ordoñez Sierra, Rodrigo; Santana, Fabiana; Molina, Johanna Marcela Duran; Cassini, Lindsey de Freitas; Alvares, Lucas de Oliveira; Quillfeldt, Jorge Alberto

2015-01-01

Memories can be destabilized by the reexposure to the training context, and may reconsolidate into a modified engram. Reconsolidation relies on some particular molecular mechanisms involving LVGCCs and GluN2B-containing NMDARs. In this study we investigate the interference caused by the presence of a distractor - a brief, unanticipated stimulus that impair a fear memory expression - during the reactivation session, and tested the hypothesis that this disruptive effect relies on a reconsolidation process. Rats previously trained in the contextual fear conditioning (CFC) were reactivated in the presence or absence of a distractor stimulus. In the test, groups reactivated in the original context with distractor displayed a reduction of the freezing response lasting up to 20 days. To check for the involvement of destabilization / reconsolidation mechanisms, we studied the effect of systemic nimodipine (a L-VGCC blocker) or intra-CA1 ifenprodil (a selective GluN2B/NMDAR antagonist) infused right before the reactivation session. Both treatments were able to prevent the disruptive effect of distraction. Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon. Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way. PMID:26328547

Management of aneurysmal subarachnoid hemorrhage.

PubMed

Etminan, N; Macdonald, R L

2017-01-01

Spontaneous subarachnoid hemorrhage (SAH) affects people with a mean age of 55 years. Although there are about 9/100 000 cases per year worldwide, the young age and high morbidity and mortality lead to loss of many years of productive life. Intracranial aneurysms account for 85% of cases. Despite this, the majority of survivors of aneurysmal SAH have cognitive deficits, mood disorders, fatigue, inability to return to work, and executive dysfunction and are often unable to return to their premorbid level of functioning. The main proven interventions to improve outcome are aneurysm repair in a timely fashion by endovascular coiling rather than neurosurgical clipping when feasible and administration of nimodipine. Management also probably is optimized by neurologic intensive care units and multidisciplinary teams. Improved diagnosis, early aneurysm repair, administration of nimodipine, and advanced neurointensive care support may be responsible for improvement in survival from SAH in the last few decades. © 2017 Elsevier B.V. All rights reserved.

Intra-arterial thrombolysis of digital artery occlusions in a patient with polycythemia vera.

PubMed

Jud, Philipp; Hafner, Franz; Gary, Thomas; Ghanim, Leyla; Lipp, Rainer; Brodmann, Marianne

2017-01-01

There are limited therapeutic options for the resolution of digital artery occlusions. Intra-arterial thrombolysis with anticoagulative and thrombolytic drugs successfully restored the blood flow in the affected digital arteries.

Pretreatment with the nitric oxide donor SNAP or nerve transection blocks humoral preconditioning by remote limb ischemia or intra-arterial adenosine.

PubMed

Steensrud, Tor; Li, Jing; Dai, Xiaojing; Manlhiot, Cedric; Kharbanda, Rajesh K; Tropak, Michael; Redington, Andrew

2010-11-01

We have previously shown that remote ischemic preconditioning (rIPC) by transient limb ischemia leads to the release of a circulating factor(s) that induces potent myocardial protection. Intra-arterial injection of adenosine into a limb also leads to cardioprotection, but the mechanism of its signal transduction is poorly understood. Eleven groups of rabbits received saline control or rIPC or adenosine administration with additional pretreatment with the nitric oxide (NO) synthase blocker N(G)-nitro-l-arginine methyl ester, the NO donor S-nitroso-N-acetylpenicillamine, its non-NO-donating derivative N-acetylpenicillamine, or femoral nerve section. Blood was then drawn from each animal, and the dialysate of the plasma was used to perfuse a naïve heart from an untreated donor. Infarct size was measured after 30 min of global ischemia and 120 min reperfusion. When compared with that of the control, mean infarct size was significantly smaller in groups treated with rIPC alone (P < 0.01) and intra-arterial adenosine (P < 0.01). Pretreatment with N(G)-nitro-l-arginine methyl ester or N-acetylpenicillamine did not affect the level of protection induced by rIPC (P = not significant, compared with rIPC alone) or intra-arterial adenosine (P = not significant, compared with intra-arterial adenosine alone), but prior femoral nerve transection or pretreatment with S-nitroso-N-acetylpenicillamine abolished the cardioprotective effect of intra-arterial adenosine and rIPC. Intra-arterial adenosine, like rIPC, releases a blood-borne cardioprotective factor(s) that is dependent on an intact femoral nerve and is inhibited by pretreatment with a NO donor. These results may be important when designing or assessing the results of clinical trials of adenosine or rIPC cardioprotection, where NO donors are used as part of therapy.

Results of an International Survey on the Investigation and Endovascular Management of Cerebral Vasospasm and Delayed Cerebral Ischemia.

PubMed

Hollingworth, Milo; Chen, Peng Roc; Goddard, Antony J P; Coulthard, Alan; Söderman, Michael; Bulsara, Ketan R

2015-06-01

Delayed cerebral ischemia (DCI) is a major cause of morbidity and mortality in aneurysmal subarachnoid hemorrhage. Endovascular management of this condition offers a new hope in preventing adverse outcome; however, a uniform standard of practice is lacking owing to a paucity of clinical trials. We conducted an international survey on the use of investigative and endovascular techniques in the treatment of DCI to assess the variability of current practice. Neurovascular neurosurgeons and neuroradiologists were contacted through professional societies from America, United Kingdom, Europe, and Australasia. Members were invited to complete a 13-item questionnaire regarding screening techniques, first-line and second-line therapies in endovascular intervention, and the role of angioplasty. Answers were compared using χ(2) testing for nonparametric data. Data from 344 respondents from 32 countries were analyzed: 167 non-United States and 177 U.S. More than half of all clinicians had 10+ years of experience in units with a mixture of higher and lower case volumes. Daily transcranial Doppler ultrasonography was the most commonly used screening technique by both U.S. (70%) and non-U.S. (53%) practitioners. Verapamil was the most common first-line therapy in the United States, whereas nimodipine was most popular in non-U.S. countries. Angioplasty was performed by 83% of non-U.S. and 91% of U.S. clinicians in the treatment of vasospasm; however, more U.S. clinicians reported using angioplasty for distal vasospasm. Treatment practices for DCI vary considerably, with the greatest variability in the choice of agent for intra-arterial therapy. Our data demonstrate the wide variation of approaches in use at present. However, without further clinical trials and development of a uniform standard of best practice, variability in treatment and outcome for DCI is likely to continue. Copyright © 2015 Elsevier Inc. All rights reserved.

Plasminogen Activators and Ischemic Stroke: Conditions for Acute Delivery

PubMed Central

del Zoppo, Gregory J

2013-01-01

Appropriate acute treatment with plasminogen activators (PAs) can significantly increase the probability of minimal or no disability in selected ischemic stroke patients. There is a great deal of evidence showing that intravenous recombinant tissue PAs (rt-PA) infusion accomplishes this goal, recanalization with other PAs has also been demonstrated in the development of this treatment. Recanalization of symptomatic, documented carotid or vertebrobasilar arterial territory occlusions have also been achieved by local intra-arterial PA delivery, although only a single prospective double-blinded randomized placebo-controlled study has been reported. The increase in intracerebral hemorrhage with these agents by either delivery approach underscores the need for careful patient selection, dose-appropriate safety and efficacy, proper clinical trial design, and an understanding of the evolution of cerebral tissue injury due to focal ischemia. Principles underlying the evolution of focal ischemia have been expanded by experience with acute PA intervention. Several questions remain open that concern the manner in which PAs can be applied acutely in ischemic stroke and how injury development can be limited. PMID:23539414

Tissue damage caused by the intramuscular injection of long-acting penicillin.

PubMed

Schanzer, H; Jacobson, J H

1985-04-01

In order to elucidate whether tissue damage produced on occasion by intramuscular injection of long-acting penicillin is due to accidental intra-arterial injection or vasospasm, two types of experiments were carried out in rabbits. In the first set of experiments, six New Zealand White rabbits were given intra-arterial injections of 0.4 mL of a mixture containing 300,000 U of penicillin G benzathine and 300,000 units of penicillin procaine per milliliter (Bicillin C-R) into the left femoral artery and 0.4 mL of normal saline into the right femoral artery as autocontrol. In a second set of experiments, 0.4 mL of the same penicillin preparation was injected in the space surrounding the left femoral artery in five New Zealand rabbits, and 0.4 mL of normal saline was injected in a similar fashion around the right femoral artery as control. The legs of the rabbits that received the intra-arterial injection of penicillin invariably developed ischemic manifestations. None of the legs of rabbits given intra-arterial injections of normal saline had pathologic manifestations. None of the rabbits that received the periarterial penicillin preparation or normal saline developed abnormalities. These results strongly suggest that the tissue damage produced by penicillin is secondary to the intra-arterial administration of the drug.

Vasodilatory responsiveness to adenosine triphosphate in ageing humans.

PubMed

Kirby, Brett S; Crecelius, Anne R; Voyles, Wyatt F; Dinenno, Frank A

2010-10-15

Endothelium-dependent vasodilatation is reduced with advancing age in humans, as evidenced by blunted vasodilator responsiveness to acetylcholine (ACh). Circulating adenosine triphosphate (ATP) has been implicated in the control of skeletal muscle vascular tone during mismatches in oxygen delivery and demand (e.g. exercise) via binding to purinergic receptors (P2Y) on the endothelium evoking subsequent vasodilatation, and ageing is typically associated with reductions in muscle blood flow under such conditions. Therefore, we tested the hypothesis that ATP-mediated vasodilatation is impaired with age in healthy humans. We measured forearm blood flow (venous occlusion plethysmography) and calculated vascular conductance (FVC) responses to local intra-arterial infusions of ACh, ATP, and sodium nitroprusside (SNP) before and during ascorbic acid (AA) infusion in 13 young and 13 older adults. The peak increase in FVC to ACh was significantly impaired in older compared with young adults (262 ± 71% vs. 618 ± 97%; P < 0.05), and this difference was abolished during AA infusion (510 ± 82% vs. 556 ± 71%; not significant, NS). In contrast, peak FVC responses were not different between older and young adults to either ATP (675 ± 105% vs. 734 ± 126%) or SNP (1116 ± 111% vs. 1138 ± 148%) and AA infusion did not alter these responses in either age group (both NS). In another group of six young and six older adults, we determined whether vasodilator responses to adenosine and ATP were influenced by P1-receptor blockade via aminophylline. The peak FVC responses to adenosine were not different in young (350 ± 65%) versus older adults (360 ± 80%), and aminophylline blunted these responses by ∼50% in both groups. The peak FVC responses to ATP were again not different in young and older adults, and aminophylline did not impact the vasodilatation in either group. Thus, in contrast to the observed impairments in ACh responses, the vasodilatory response to exogenous ATP is not reduced with age in healthy humans. Further, our data also indicate that adenosine mediated vasodilatation is not reduced with age, and that ATP-mediated vasodilatation is independent of P1-receptor stimulation in both young and older adults.

Use of intra-arterial nitroglycerin during uterine artery embolization for severe postpartum hemorrhage with uterine artery vasospasm.

PubMed

Wang, Liangcheng; Horiuchi, Isao; Mikami, Yukiko; Takagi, Kenjiro; Okochi, Tomohisa; Hamamoto, Kohei; Chiba, Emiko; Matsuura, Katsuhiko

2015-04-01

Uterine artery embolization (UAE) is a standard method for treating postpartum hemorrhage (PPH), although uterine artery vasospasm during UAE may lead to failure of hemostasis. Here, we report our experience with a case of PPH in which the bleeding was successfully controlled by intra-arterial administration of nitroglycerin during the second UAE. A 30-year-old woman experienced PPH following a successful cesarean section, and a UAE was performed. However, 6 hours later, vaginal bleeding restarted; the reason for unsuccessful embolization during the first UAE was vasoconstriction due to hypovolemic shock. We performed a second UAE, but uterine bleeding continued. After intra-arterial administration of nitroglycerin, hemostasis was confirmed, and there was no reperfusion of the uterine artery. After these two UAE procedures, no recurrence of bleeding was observed. Thus, use of intra-arterial nitroglycerin was effective for controlling uterine artery vasospasm during UAE. However, larger studies are required to confirm these findings. Copyright © 2015. Published by Elsevier B.V.

Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice.

PubMed

Moreno, Lina Clara Gayoso E Almendra Ibiapina; Rolim, Hercília Maria Lins; Freitas, Rivelilson Mendes; Santos-Magalhães, Nereide Stela

2016-09-01

Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular dynamics study of the encapsulation capability of a PCL-PEO based block copolymer for hydrophobic drugs with different spatial distributions of hydrogen bond donors and acceptors.

PubMed

Patel, Sarthak K; Lavasanifar, Afsaneh; Choi, Phillip

2010-03-01

Molecular dynamics simulation was used to study the potential of using a block copolymer containing three poly(epsilon-caprolactone) (PCL) blocks of equal length connected to one end of a poly(ethylene oxide) (PEO) block, designated as PEO-b-3PCL, to encapsulate two classes of hydrophobic drugs with distinctively different molecular structures. In particular, the first class of drugs consisted of two cucurbitacin drugs (CuB and CuI) that contain multiple hydrogen bond donors and acceptors evenly distributed on their molecules while the other class of drugs (fenofibrate and nimodipine) contain essentially only clustered hydrogen bond acceptors. In the case of cucurbitacin drugs, the results showed that PEO-b-3PCL lowered the Flory-Huggins interaction parameters (chi) considerably (i.e., increased the drug solubility) compared to the linear di-block copolymer PEO-b-PCL with the same PCL/PEO (w/w) ratio of 1.0. However, the opposite effect was observed for fenofibrate and nimodipine. Analysis of the intermolecular interactions indicates that the number of hydrogen bonds formed between the three PCL blocks and cucurbitacin drugs is significantly higher than that of the linear di-block copolymer. On the other hand, owing to the absence of hydrogen bond donors and the clustering of the hydrogen bond acceptors on the fenofibrate and nimodipine molecules, this significantly reduces the number of hydrogen bonds formed in the multi-PCL block environment, leading to unfavourable chi values. The findings of the present work suggest that multi-hydrophobic block architecture could potentially increase the drug loading for hydrophobic drugs with structures containing evenly distributed multiple hydrogen bond donors and acceptors. (c) 2009 Elsevier Ltd. All rights reserved.

The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice.

PubMed

Wang, Weijie; Yu, Yingcong; Li, Jing; Wang, Lin; Li, Zhi; Zhang, Chong; Zhen, Linlin; Ding, Lianshu; Wang, Gang; Sun, Xiaoyang; Xu, Ying

2017-08-01

Resveratrol has been widely studied in terms of it's potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca 2+ /calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca 2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl 2 , ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca 2+ , however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl 2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.

Intentional intra-arterial injection of midazolam in a patient with status epilepticus in the Intensive Care Unit

PubMed Central

Ali, Muhammad Asghar; Yahya, Muhammad

2017-01-01

Fundamental medical care includes intravenous (IV) access which provides prompt resuscitation and reliable delivery of analgesics, antibiotics, and vasoactive medication. Difficult access populations, especially in critical area, continue to challenge providers to consider and utilize alternative means to provide IV access. Potential options under such circumstances include intramuscular, intraosseous, and intratracheal drug administration, but in extreme cases where no other options are available, intra-arterial route might be considered. We present a case where midazolam was intentionally injected intra-arterially to abort seizure activity in a patient with status epilepticus in the Intensive Care Unit. PMID:29033730

Cost identification of abdominal aortic aneurysm imaging by using time and motion analyses.

PubMed

Rubin, G D; Armerding, M D; Dake, M D; Napel, S

2000-04-01

To compare the costs of performing helical computed tomographic (CT) angiography with three-dimensional rendering versus intraarterial digital subtraction angiography (DSA) for preoperative imaging of abdominal aortic aneurysms (AAAs). A single observer determined the variable direct costs of performing nine intraarterial DSA and 10 CT angiographic examinations in age- and general health-matched patients with AAA by using time and motion analyses. All personnel directly involved in the cases were tracked, and the involvement times were recorded to the nearest minute. All material items used during the procedures were recorded. The cost of labor was determined from personnel reimbursement data, and the cost of materials, from vendor pricing. The variable direct costs of laboratory tests and using the ambulatory treatment unit for postprocedural monitoring, as well as all fixed direct costs, were assessed from hospital accounting records. The total costs were determined for each procedure and compared by using the Student t test and calculating the CIs. The mean total direct cost of intraarterial DSA (+/- SD) was $1,052 +/- 71, and that of CT angiography was $300 +/- 30, which are significantly different (P < 4.1 x 10(-11)). With 95% confidence, intraarterial DSA cost 3.2-3.7 times more than CT angiography for the assessment of AAA. Assuming equal diagnostic utility and procedure-related morbidity, institutions may have substantial cost savings whenever CT angiography can replace intraarterial DSA for imaging AAAs.

Evaluation of Cisplatin Neurotoxicity in Cultured Rat Dorsal Root Ganglia via Cytosolic Calcium Accumulation

PubMed Central

Erol, Kevser; Yiğitaslan, Semra; Ünel, Çiğdem; Kaygısız, Bilgin; Yıldırım, Engin

2016-01-01

Background: Calcium homeostasis is considered to be important in antineoplastic as well as in neurotoxic adverse effects of cisplatin. Aims: This study aimed to investigate the role of Ca2+ in cisplatin neurotoxicity in cultured rat dorsal root ganglia (DRG) cells. Study Design: Cell culture study. Methods: DRG cells prepared from 1-day old Sprague-Dawley rats were used to determine the role of Ca2+ in the cisplatin (10–600 μM) neurotoxicity. The cells were incubated with cisplatin plus nimodipine (1–3 μM), dizocilpine (MK-801) (1–3 μM) or thapsigargin (100–300 nM). Toxicity of cisplatinon DRG cells was determined by the MTT assay. Results: The neurotoxicity of cisplatin was significant when used in high concentrations (100–600 μM). Nimodipine (1 μM) but not MK-801 or thapsigargin prevented the neurotoxic effects of 200 μM of cisplatin. Conclusion: Voltage-dependent calcium channels may play a role in cisplatin neurotoxicity. PMID:27403382

Outcome Differences between Intra-Arterial Iso- and Low-Osmolality Iodinated Radiographic Contrast Media in the Interventional Management of Stroke III Trial.

PubMed

Tomsick, T A; Foster, L D; Liebeskind, D S; Hill, M D; Carrozella, J; Goyal, M; von Kummer, R; Demchuk, A M; Dzialowski, I; Puetz, V; Jovin, T; Morales, H; Palesch, Y Y; Broderick, J; Khatri, P; Yeatts, S D

2015-11-01

Intracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III). We reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model. Of baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol. While data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation. © 2015 by American Journal of Neuroradiology.

Transradial Approach for Hepatic Radioembolization: Initial Results and Technique.

PubMed

Bishay, Vivian L; Biederman, Derek M; Ward, Thomas J; van der Bom, Imramsjah Martijn J; Patel, Rahul S; Kim, Edward; Nowakowski, Francis S; Lookstein, Robert A; Fischman, Aaron M

2016-11-01

The transradial approach (TRA) has been shown to reduce the morbidity and mortality associated with arterial coronary interventions. Selective internal radiation therapy (SIRT) performed via the TRA can enhance patient comfort, compared with the traditional transfemoral approach (TFA), by allowing immediate ambulation and precluding potential complications associated with the TFA, such as closure device injury or retroperitoneal hematoma. We report our initial experience with and technique for using the TRA for SIRT. Between May 1, 2012, and April 30, 2015, a total of 574 procedures, including planning angiograms (n = 329) and infusions of 90 Y (n = 245), were performed for 318 patients (mean age, 64.5 years). Of the 245 patients who received 90 Y infusions, 52 had SIRT performed with the use of a permanent single-use implant of 90 Y resin microspheres and 193 had SIRT performed with the use of millions of small glass microspheres containing radioactive 90 Y. Procedural details, technical success, the radial artery (RA) occlusion rate noted at 30 days (as assessed via pulse examination), and the major and minor adverse events noted at 30 days were evaluated. Technical success was achieved in 561 of 574 cases (97.7%). The reasons for crossover to use of the TFA included an RA loop (n = 2), RA occlusion (n = 9), and type D response as determined by use of a Barbeau test (n = 2). Patients had undergone between zero and six previous TRA procedures. The mortality rate at 30 days was 0%. Superficial bruising occurred in 13 of 574 cases (2.3%). A grade 2 hematoma that required a second nonocclusive hemostasis cuff occurred in one case. Transient forearm numbness or pain occurred in two of 574 cases. One patient had a transient convulsive event occur after receiving intraarterial infusion of verapamil. RA occlusion occurred in nine of 574 cases (1.6%). Use of the TRA for SIRT is safe, feasible, and well tolerated and is associated with high rates of technical success and rare complications.

Angiographic evaluation of the effect of intra-arterial milrinone therapy in patients with vasospasm from aneurysmal subarachnoid hemorrhage.

PubMed

Shankar, Jai Jai Shiva; dos Santos, Marlise P; Deus-Silva, Leonardo; Lum, Cheemun

2011-02-01

Several methods have been used to treat cerebral vasospasm, which is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (SAH). Here, we examined the effectiveness and safety of intra-arterial injection of milrinone for the treatment of vasospasm. Consecutive patients with angiographically confirmed vasospasm received intra-arterial milrinone between January 2006 and December 2007. The improvement in diameter of vessel (in millimeters) following treatment was assessed by paired t test for statistical significance. The angiographic improvement of supraclinoid internal carotid artery, M1 segment of middle cerebral artery, and A1 and A2 segment of anterior cerebral artery was compared with the modified Rankin score of the patients at discharge. A total of 15 milrinone treatments were performed in 14 patients (11 females and 3 males) with mean age of 52.7 years (31-68 years). There was significant angiographic improvement after milrinone therapy (p < 0.0001). Intra-arterial milrinone was a safe and effective treatment of cerebral vasospasm following aneurysmal SAH.

Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes.

PubMed

Mocan, Lucian; Tabaran, Flaviu A; Mocan, Teodora; Bele, Constantin; Orza, Anamaria Ioana; Lucan, Ciprian; Stiufiuc, Rares; Manaila, Ioana; Iulia, Ferencz; Dana, Iancu; Zaharie, Florin; Osian, Gelu; Vlad, Liviu; Iancu, Cornel

2011-01-01

The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called "nanophotothermolysis". We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion.

Pharmacological Approaches to Performance Enhancement in Animals,

DTIC Science & Technology

found to improve performance disrupted by exposure to hypoxia. These substances included piracetam , nimodipine, and ipsapirone. An additional...their low toxicity , and their lack of negative effects on normal cognitive performance, it is suggested that these drugs could prove to be useful therapeutic agents under conditions of high information processing load.

Neurotransmitter Amines in Hemorrhagic Shock.

DTIC Science & Technology

1984-03-02

and synthesis for future studies. Crit Care Med 11:202-207, 1983. 7. Gelmer HJ: Effect of ninodipine (Bay e 9736) on post-ischaemic- cerebro - vascular...the calcium antagonist, nimodipine on cerebral blood flow and metabolism in the primate . JCereb Blood Flow and Metabol 1:349-356, 1981. 9. Edvinsson L

Adenosine receptor antagonist and augmented vasodilation during hypoxic exercise

PubMed Central

Madery, Brandon D.; Pike, Tasha L.; Eisenach, John H.; Dietz, Niki M.; Joyner, Michael J.; Wilkins, Brad W.

2009-01-01

We tested the hypothesis that adenosine contributes to augmented skeletal muscle vasodilation during hypoxic exercise. In separate protocols, subjects performed incremental rhythmic forearm exercise (10% and 20% of maximum) during normoxia and normocapnic hypoxia (80% arterial O2 saturation). In protocol 1 (n = 8), subjects received an intra-arterial administration of saline (control) and aminophylline (adenosine receptor antagonist). In protocol 2 (n = 10), subjects received intra-arterial phentolamine (α-adrenoceptor antagonist) and combined phentolamine and aminophylline administration. Forearm vascular conductance (FVC; in ml·min−1·100 mmHg−1) was calculated from forearm blood flow (in ml/min) and blood pressure (in mmHg). In protocol 1, the change in FVC (ΔFVC; change from normoxic baseline) during hypoxic exercise with saline was 172 ± 29 and 314 ± 34 ml·min−1·100 mmHg−1 (10% and 20%, respectively). Aminophylline administration did not affect ΔFVC during hypoxic exercise at 10% (190 ± 29 ml·min−1·100 mmHg−1, P = 0.4) or 20% (287 ± 48 ml·min−1·100 mmHg−1, P = 0.3). In protocol 2, ΔFVC due to hypoxic exercise with phentolamine infusion was 313 ± 30 and 453 ± 41 ml·min−1·100 mmHg−1 (10% and 20% respectively). ΔFVC was similar at 10% (352 ± 39 ml·min−1·100 mmHg−1, P = 0.8) and 20% (528 ± 45 ml·min−1·100 mmHg−1, P = 0.2) hypoxic exercise with combined phentolamine and aminophylline. In contrast, ΔFVC to exogenous adenosine was reduced by aminophylline administration in both protocols (P < 0.05 for both). These observations suggest that adenosine receptor activation is not obligatory for the augmented hyperemia during hypoxic exercise in humans. PMID:19661449

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

A murine model of targeted infusion for intracranial tumors.

PubMed

Kim, Minhyung; Barone, Tara A; Fedtsova, Natalia; Gleiberman, Anatoli; Wilfong, Chandler D; Alosi, Julie A; Plunkett, Robert J; Gudkov, Andrei; Skitzki, Joseph J

2016-01-01

Historically, intra-arterial (IA) drug administration for malignant brain tumors including glioblastoma multiforme (GBM) was performed as an attempt to improve drug delivery. With the advent of percutaneous neuorovascular techniques and modern microcatheters, intracranial drug delivery is readily feasible; however, the question remains whether IA administration is safe and more effective compared to other delivery modalities such as intravenous (IV) or oral administrations. Preclinical large animal models allow for comparisons between treatment routes and to test novel agents, but can be expensive and difficult to generate large numbers and rapid results. Accordingly, we developed a murine model of IA drug delivery for GBM that is reproducible with clear readouts of tumor response and neurotoxicities. Herein, we describe a novel mouse model of IA drug delivery accessing the internal carotid artery to treat ipsilateral implanted GBM tumors that is consistent and reproducible with minimal experience. The intent of establishing this unique platform is to efficiently interrogate targeted anti-tumor agents that may be designed to take advantage of a directed, regional therapy approach for brain tumors.

Interventional management of gastroduodenal lesions complicating intra-arterial hepatic chemotherapy.

PubMed

Proietti, Stefania; De Baere, Thierry; Bessoud, Bertrand; Doenz, Francesco; Qanadli, Salah Dine; Schnyder, Pierre; Denys, Alban

2007-08-01

Herein we report the efficacy of embolization of small patent gastric or duodenal vessels for treating gastroduodenal complications after hepatic arterial infusion therapy (HAIC). Catheter ports were implanted percutaneously from a femoral approach in three cases or surgically in the gastroduodenal artery in two cases. Acute abdominal pain developed on average after four HAIC courses of 5FU-oxaliplatin, mytomycin, oxaliplatin or fotemustine. Esophagogastroduodenoscopy showed gastroduodenal lesions (gastroduodenitis with or without ulcerations) in all cases. Despite the interruption of the HAIC, symptoms persisted and led to selective hepatic arteriography showing a patent right gastric artery (n = 4) or a recanalized gastroduodenal artery (n = 1) responsible for gastroduodenal misperfusion. Successful embolizations of the arteries responsible for gastroduodenal misperfusion (right gastric artery in four cases and gastroduodenal artery in one case) using 0.018 platinium coils relieved the patients' symptoms and allowed the HAIC to continue. In gastroduodenal complications of HAIC, a selective hepatic arteriography should be performed to search any artery responsible for the misperfusion of the toxic agent in the gastroduodenal area. Embolization of these arteries allowed the HAIC to be restored.

Intracarotid administration of short-chain alkylglycerols for increased delivery of methotrexate to the rat brain.

PubMed

Erdlenbruch, Bernhard; Schinkhof, Claudia; Kugler, Wilfried; Heinemann, Dagmar E H; Herms, Jochen; Eibl, Hansjörg; Lakomek, Max

2003-06-01

1 The intracarotid administration of alkylglycerols has been reported previously by us to be a novel strategy for increased delivery of various chemotherapeutic drugs to the normal brain and brain tumors in rats. 2 Effectiveness and structure-activity relations of the most promising pentyl- and hexylglycerol derivatives have been elucidated in vivo by analyzing the transfer of methotrexate (MTX) across the blood-brain barrier (BBB) in normal rats. The effects were compared with BBB disruption using hypertonic mannitol or intracarotid infusion of bradykinin. Furthermore, toxicity of the alkylglycerols has been studied in long-term experiments. 3 Apart from 1-O-pentyldiglycerol, all alkylglycerols induced a concentration-dependent increase in MTX delivery to the brain varying from 1.1 to more than 300-fold compared to intra-arterial MTX alone. Enhanced barrier permeability rapidly approached baseline values within 5 and 120 min at the latest. Chemical structure, concentration, time schedule of injections and combination of different alkylglycerols were identified as instruments suited to regulate the MTX accumulation within a wide range. Mannitol 1.4 M resulted in very high MTX levels in the brain as observed using the highest concentrations of alkylglycerols. Intracarotid infusion of bradykinin had only a minor effect on the BBB. Using 1-O-pentylglycerol or 2-O-hexyldiglycerol, both cell culture experiments and long-term in vivo analyses including clinical, laboratory and histopathological evaluations revealed no signs of toxicity. 4 In summary, intracarotid short-chain alkylglycerols constitute a very effective and low toxic strategy for transient opening of the BBB to overcome the limited access of cytotoxic drugs to the brain.

Intracarotid administration of short-chain alkylglycerols for increased delivery of methotrexate to the rat brain

PubMed Central

Erdlenbruch, Bernhard; Schinkhof, Claudia; Kugler, Wilfried; Heinemann, Dagmar E H; Herms, Jochen; Eibl, Hansjörg; Lakomek, Max

2003-01-01

The intracarotid administration of alkylglycerols has been reported previously by us to be a novel strategy for increased delivery of various chemotherapeutic drugs to the normal brain and brain tumors in rats. Effectiveness and structure–activity relations of the most promising pentyl- and hexylglycerol derivatives have been elucidated in vivo by analyzing the transfer of methotrexate (MTX) across the blood–brain barrier (BBB) in normal rats. The effects were compared with BBB disruption using hypertonic mannitol or intracarotid infusion of bradykinin. Furthermore, toxicity of the alkylglycerols has been studied in long-term experiments. Apart from 1-O-pentyldiglycerol, all alkylglycerols induced a concentration-dependent increase in MTX delivery to the brain varying from 1.1 to more than 300-fold compared to intra-arterial MTX alone. Enhanced barrier permeability rapidly approached baseline values within 5 and 120 min at the latest. Chemical structure, concentration, time schedule of injections and combination of different alkylglycerols were identified as instruments suited to regulate the MTX accumulation within a wide range. Mannitol 1.4 M resulted in very high MTX levels in the brain as observed using the highest concentrations of alkylglycerols. Intracarotid infusion of bradykinin had only a minor effect on the BBB. Using 1-O-pentylglycerol or 2-O-hexyldiglycerol, both cell culture experiments and long-term in vivo analyses including clinical, laboratory and histopathological evaluations revealed no signs of toxicity. In summary, intracarotid short-chain alkylglycerols constitute a very effective and low toxic strategy for transient opening of the BBB to overcome the limited access of cytotoxic drugs to the brain. PMID:12812991

Specific endothelin ET(A) receptor antagonism does not modulate insulin-induced hemodynamic effects in the human kidney, eye, or forearm.

PubMed

Rab, Anna; Dallinger, Susanne; Polak, Kaija; Pleiner, Johannes; Polska, Elzbieta; Wolzt, Michael; Schmetterer, Leopold

2004-05-01

There is evidence that hyperinsulinemia may stimulate endothelin-1 (ET-1) generation or release, which may affect diabetic vascular complications. BQ-123, a specific ET(A) receptor antagonist, was used to investigate if insulin-induced vascular effects are influenced by an acute ET-1 release. Two randomized, placebo-controlled, double-blind, cross-over studies were performed. In protocol 1, 12 healthy subjects received, on separate study days, infusions of BQ-123 (60 microg/min for 30 min) during placebo clamp conditions, BQ-123 during euglycemic hyperinsulinemia (3 mU/kg/min for 390 min), or placebo during euglycemic hyperinsulinemia. Fundus pulsation amplitude (FPA) was measured to assess pulsatile choroidal blood flow, and mean flow velocity (MFV) of the ophtalmic artery was measured by color Doppler imaging. In protocol 2, eight healthy subjects received, on separate study days, intra-arterial infusions of BQ-123 (32 microg/min for 120 min) during placebo or insulin clamp. Forearm blood flow was measured with bilateral plethysmography, expressing the ratio of responses in the intervention arm and in the control arm. Insulin alone increased FPA (+10%, p < 0.001) and forearm blood flow (+19%). BQ-123 increased FPA, MFV, and forearm blood flow ratio in the absence and presence of exogenous insulin, but this effect was not different between normo- and hyperinsulinemic conditions. ET-1 plasma concentrations were not affected by insulin. In conclusion, these data do not support the concept that hyperinsulinemia increases ET-1 generation in healthy subjects. Our results, however, cannot necessarily be extrapolated to diabetic and obese subjects.

Selective ex-vivo photothermal ablation of human pancreatic cancer with albumin functionalized multiwalled carbon nanotubes

PubMed Central

Mocan, Lucian; Tabaran, Flaviu A; Mocan, Teodora; Bele, Constantin; Orza, Anamaria Ioana; Lucan, Ciprian; Stiufiuc, Rares; Manaila, Ioana; Iulia, Ferencz; Dana, Iancu; Zaharie, Florin; Osian, Gelu; Vlad, Liviu; Iancu, Cornel

2011-01-01

The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called “nanophotothermolysis”. We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion. PMID:21720504

Retinoblastoma and optic nerve enhancement in a brain magnetic resonance scan: is it always a metastasis?

PubMed

Correa-Acosta, A; González-Alviar, M E; Gaviria-Bravo, M L

2018-05-01

The case is presented on a girl with a unilateral retinoblastoma that required treatment with intra-arterial chemotherapy. In the nuclear magnetic resonance imaging of the brain performed 1 month after intra-arterial chemotherapy treatment, post-laminar optic nerve (ON) enhancement was observed, leading to the suspicion of an ON tumour infiltration. Additional examinations were requested by which a probable optic neuropathy was diagnosed. The ON enhancement in magnetic resonance imaging of the brain in retinoblastoma generally corresponds to tumour invasion of the ON. However, other diagnostic alternatives associated with the use of new treatments, such as intra-arterial chemotherapy, should be considered. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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

Radeleff, B., E-mail: Boris_radeleff@med.uni-heidelberg.de; Stampfl, U.; Sommer, C.-M.

2011-10-15

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

Hemodynamic and neurohumoral effects of various grades of selective adenosine transport inhibition in humans. Implications for its future role in cardioprotection.

PubMed

Rongen, G A; Smits, P; Ver Donck, K; Willemsen, J J; De Abreu, R A; Van Belle, H; Thien, T

1995-02-01

In 12 healthy male volunteers (27-53 yr), a placebo-controlled randomized double blind cross-over trial was performed to study the effect of the intravenous injection of 0.25, 0.5, 1, 2, 4, and 6 mg draflazine (a selective nucleoside transport inhibitor) on hemodynamic and neurohumoral parameters and ex vivo nucleoside transport inhibition. We hypothesized that an intravenous draflazine dosage without effect on hemodynamic and neurohumoral parameters would still be able to augment the forearm vasodilator response to intraarterially infused adenosine. Heart rate (electrocardiography), systolic blood pressure (Dinamap 1846 SX; Critikon, Portanje Electronica BV, Utrecht, The Netherlands) plasma norepinephrine and epinephrine increased dose-dependently and could almost totally be abolished by caffeine pretreatment indicating the involvement of adenosine receptors. Draflazine did not affect forearm blood flow (venous occlusion plethysmography). Intravenous injection of 0.5 mg draflazine did not affect any of the measured hemodynamic parameters but still induced a significant ex vivo nucleoside-transport inhibition of 31.5 +/- 4.1% (P < 0.05 vs placebo). In a subgroup of 10 subjects the brachial artery was cannulated to infuse adenosine (0.15, 0.5, 1.5, 5, 15, and 50 micrograms/100 ml forearm per min) before and after intravenous injection of 0.5 mg draflazine. Forearm blood flow amounted 1.9 +/- 0.3 ml/100 ml forearm per min for placebo and 1.8 +/- 0.2, 2.0 +/- 0.3, 3.8 +/- 0.9, 6.3 +/- 1.2, 11.3 +/- 2.2, and 19.3 +/- 3.9 ml/100 ml forearm per min for the six incremental adenosine dosages, respectively. After the intravenous draflazine infusion, these values were 1.6 +/- 0.2 ml/100 ml forearm per min for placebo and 2.1 +/- 0.3, 3.3 +/- 0.6, 5.8 +/- 1.1, 6.9 +/- 1.4, 14.4 +/- 2.9, and 23.5 +/- 4.0 ml/100 ml forearm per min, respectively (Friedman ANOVA: P < 0.05 before vs after draflazine infusion). In conclusion, a 30-50% inhibition of adenosine transport significantly augments the forearm vasodilator response to adenosine without significant systemic effects. These results suggest that draflazine is a feasible tool to potentiate adenosine-mediated cardioprotection in man.

N-acetylcysteine does not influence the activity of endothelium-derived relaxing factor in vivo.

PubMed

Creager, M A; Roddy, M A; Boles, K; Stamler, J S

1997-02-01

Nitric oxide forms complexes with an array of biomolecular carriers that retain biological activity. This reactivity of nitric oxide in physiological systems has led to some dispute as to whether endothelium-derived relaxing factors nitric oxide or a closely related adduct thereof, such as a nitrosothiol. In vitro bioassays used to address this question are limited by the exclusion of biological thiols that are requisite for nitrosothiol formation. Thus, the purpose of this study was to obtain insight into the identity of endothelium-derived relaxing factor in vivo. We reasoned that if endothelium-derived relaxing factor in nitric oxide, infusion of physiological concentrations of thiol would potentiate its bioactivity by analogy with effects seen in vitro, whereas nitrosothiol would be resistant to such modulation. We used venous-occlusion plethysmography to study forearm blood flow in normal subjects. Methacholine (0.3 to 10 micrograms/min) and nitroglycerin (1 to 30 micrograms/min) were infused via the brachial artery to elicit endothelium-dependent and endothelium-independent vasodilation, respectively. Dose-response determinations were made for each drug before and after an intra-arterial infusion of the reduced thiol, N-acetylcysteine, at rates estimated to achieve a physiological concentration of 1 mmol/L. Methacholine increased forearm blood flow in a dose-dependent manner. Infusion of N-acetylcysteine did not change the sensitivity (ED50, 1.7 versus 1.7 micrograms/min, P = NS) or maximal response to methacholine. In contrast, thiol increased the sensitivity to nitroglycerin (ED50, 4.7 versus 2.8 micrograms/min, P < .01). Thus, conflicting with reports in vitro, thiol does not modulate endothelium-derived relaxing factor responses in vivo. These data indicate that sulfhydryl groups are not a limiting factor for endothelium-derived relaxing factor responses in forearm resistance vessels in normal humans and are in keeping with reports that nitrosothiol contributes to endothelium-derived relaxing factor bioactivity in plasma and vascular smooth muscle. Potentiation of the effects of nitroglycerin by N-acetylcysteine can be attributed to its enhanced biotransformation to an endothelium-derived relaxing factor equivalent, such as nitrosothiol. These observations support the notion of an equilibrium between nitric oxide and nitrosothiol in biological systems that may be influenced by redox state.

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

Madaric, Juraj, E-mail: jurmad@hotmail.com; Klepanec, Andrej; Mistrik, Martin

Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

Admission Glucose and Effect of Intra-Arterial Treatment in Patients With Acute Ischemic Stroke.

PubMed

Osei, Elizabeth; den Hertog, Heleen M; Berkhemer, Olvert A; Fransen, Puck S S; Roos, Yvo B W E M; Beumer, Debbie; van Oostenbrugge, Robert J; Schonewille, Wouter J; Boiten, Jelis; Zandbergen, Adrienne A M; Koudstaal, Peter J; Dippel, Diederik W J

2017-05-01

Hyperglycemia on admission is common after ischemic stroke. It is associated with unfavorable outcome after treatment with intravenous thrombolysis and after intra-arterial treatment. Whether hyperglycemia influences the effect of reperfusion treatment is unknown. We assessed whether increased admission serum glucose modifies the effect of intra-arterial treatment in patients with acute ischemic stroke. We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose >7.8 mmol/L. The primary outcome measure was the adjusted common odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale at 90 days, estimated with ordinal logistic regression. Secondary outcome variable was symptomatic intracranial hemorrhage. We assessed treatment effect modification of hyperglycemia and admission serum glucose levels with multiplicative interaction factors and adjusted for prognostic variables. Four hundred eighty-seven patients were included. Mean admission serum glucose was 7.2 mmol/L (SD, 2.2). Fifty-seven of 226 patients (25%) randomized to intra-arterial treatment were hyperglycemic compared with 61 of 261 patients (23%) in the control group. The interaction of either hyperglycemia or admission serum glucose levels and treatment effect on modified Rankin Scale scores was not significant ( P =0.67 and P =0.87, respectively). The same applied for occurrence of symptomatic hemorrhage ( P =0.39 for hyperglycemia, P =0.39 for admission serum glucose). We found no evidence for effect modification of intra-arterial treatment by admission serum glucose in patients with acute ischemic stroke. URL: www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

Comparison of classification methods for voxel-based prediction of acute ischemic stroke outcome following intra-arterial intervention

NASA Astrophysics Data System (ADS)

Winder, Anthony J.; Siemonsen, Susanne; Flottmann, Fabian; Fiehler, Jens; Forkert, Nils D.

2017-03-01

Voxel-based tissue outcome prediction in acute ischemic stroke patients is highly relevant for both clinical routine and research. Previous research has shown that features extracted from baseline multi-parametric MRI datasets have a high predictive value and can be used for the training of classifiers, which can generate tissue outcome predictions for both intravenous and conservative treatments. However, with the recent advent and popularization of intra-arterial thrombectomy treatment, novel research specifically addressing the utility of predictive classi- fiers for thrombectomy intervention is necessary for a holistic understanding of current stroke treatment options. The aim of this work was to develop three clinically viable tissue outcome prediction models using approximate nearest-neighbor, generalized linear model, and random decision forest approaches and to evaluate the accuracy of predicting tissue outcome after intra-arterial treatment. Therefore, the three machine learning models were trained, evaluated, and compared using datasets of 42 acute ischemic stroke patients treated with intra-arterial thrombectomy. Classifier training utilized eight voxel-based features extracted from baseline MRI datasets and five global features. Evaluation of classifier-based predictions was performed via comparison to the known tissue outcome, which was determined in follow-up imaging, using the Dice coefficient and leave-on-patient-out cross validation. The random decision forest prediction model led to the best tissue outcome predictions with a mean Dice coefficient of 0.37. The approximate nearest-neighbor and generalized linear model performed equally suboptimally with average Dice coefficients of 0.28 and 0.27 respectively, suggesting that both non-linearity and machine learning are desirable properties of a classifier well-suited to the intra-arterial tissue outcome prediction problem.

[Results of thrombolyses procedures in acute ischemic cerebral stroke realized in Kraków 2004-2007--Grant Ministry of Science and Information].

PubMed

Popiela, Tadeusz J; Urbanik, Andrzej; Słowik, Agnieszka

2010-01-01

To lower the number of complications of acute cerebral ischemic stroke and to reduce the time of rehabilitation in these patients it is necessary to induce treatment within the first 3 hours of the onset of the stroke. Early intervention however, is possible only in cases with the confirm localized ischemic focus visualized in one of the diagnostic imaging methods. The most widespread is CT, hovewer the first symptoms of ischemic stroke can be seen not beforel2 hours of the onset. The study evaluated the effectiveness of early diagnostics of ischemic stroke using perfusion CT (pCT) with subsequent intravenous or intra-arterial thrombolysis. The patients with ischemic stroke confirmed by pCT and qualified to thrombolysis in the first 3 hours of the onset of the stroke were randomly selected to intravenous or intra-arterial thrmobolysis. Those, who were 3 to 6 hours of the onset of the stroke were qualified to intra-arterial thrombolysis. A study group consisted of 377 patients hospitalized due to ischemic stroke. Of these pCT was performed in 76 cases, intravenous thrombolysis in 4 and intra-arterial thrombolysis in 2. Clinical condition substantially improved in 3 patients. Obtained results indicate the necessity to introduce pCT to the routine diagnostics of the acute ischemic stroke. A small number of patients eligible for thrombolysis does not allow to compare the effectiveness of intra-arterial and intravenous thrombolysis, however the project allowed to work out the efficient system of diagnostics and treatment of the acute ischemic stroke in the area of Krakow based on the standards used in the European countries.

Study of the intra-arterial distribution of Fe₃O₄ nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry.

PubMed

Echevarria-Uraga, José J; García-Alonso, Ignacio; Plazaola, Fernando; Insausti, Maite; Etxebarria, Néstor; Saiz-López, Alberto; Fernández-Ruanova, Begoña

2012-01-01

To evaluate, in an experimental model, the reliability of MRI for determining whether a higher iron concentration was obtained in tumor tissue than in normal liver parenchyma after intra-arterial administration of Fe₃O₄ lipophilic nanoparticles. WAG/RijCrl rats were inoculated in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells, after which they were randomized into two groups: control (CG) and infused (IG). After confirming tumor induction, the IG rats received intra-arterial suspensions of Fe₃O₄ nanoparticles (2.6 mg) in Lipiodol® (0.15 mL). To calculate the iron concentration, [Fe], in the tumor and liver tissues of both groups of rats, measurements of signal intensity from the tumors, healthy liver tissue, and paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*-weighted sequences. In addition, samples were collected to quantify the [Fe] by inductively coupled plasma-mass spectrometry (ICP-MS), as well as for histological analysis. Statistical analysis was performed with non-parametric tests, and Bland-Altman plots were produced; P values <0.05 were considered significant. In the CG rats (n = 23), the mean [Fe] values estimated by MRI and ICP-MS were 13.2 μmol·g⁻¹ and 5.9 μmol·g⁻¹, respectively, in the tumors, and 19.0 μmol ·g⁻¹ and 11.7 μmol·g⁻¹, respectively, in the hepatic tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9 μmol·g⁻¹ and 9.4 μmol · g⁻¹, respectively, in the tumors, and 115.3 μmol·g⁻¹ and 11.6 μmol·g⁻¹, respectively, in the healthy liver tissue. The IG results revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis between the groups regarding the [Fe] values obtained by ICP-MS, significant differences were found for the tumor samples (P < 0.001), but not for the hepatic tissue (P = 0.92). Under microscopy, scattered intravascular deposits of nanoparticles were observed, especially in the tumors. ICP-MS demonstrated significant uptake of exogenous iron in tumor tissue. MRI was useful for quantifying the [Fe] in the different tissues in the CG animals, but not in the IG animals. Although the irregular distribution of nanoparticles caused an important bias in the measurements obtained by MRI, the relative increase in iron content inside the tumor was suggested.

Study of the intra-arterial distribution of Fe3O4 nanoparticles in a model of colorectal neoplasm induced in rat liver by MRI and spectrometry

PubMed Central

Echevarria-Uraga, José J; García-Alonso, Ignacio; Plazaola, Fernando; Insausti, Maite; Etxebarria, Néstor; Saiz-López, Alberto; Fernández-Ruanova, Begoña

2012-01-01

Purpose To evaluate, in an experimental model, the reliability of MRI for determining whether a higher iron concentration was obtained in tumor tissue than in normal liver parenchyma after intra-arterial administration of Fe3O4 lipophilic nanoparticles. Materials and methods WAG/RijCrl rats were inoculated in the left hepatic lobe with 25,000 syngeneic CC-531 colon adenocarcinoma cells, after which they were randomized into two groups: control (CG) and infused (IG). After confirming tumor induction, the IG rats received intra-arterial suspensions of Fe3O4 nanoparticles (2.6 mg) in Lipiodol® (0.15 mL). To calculate the iron concentration, [Fe], in the tumor and liver tissues of both groups of rats, measurements of signal intensity from the tumors, healthy liver tissue, and paravertebral muscles were made on a 1.5T MRI system in gradient-echo DP* and T2*-weighted sequences. In addition, samples were collected to quantify the [Fe] by inductively coupled plasma-mass spectrometry (ICP-MS), as well as for histological analysis. Statistical analysis was performed with non-parametric tests, and Bland–Altman plots were produced; P values <0.05 were considered significant. Results In the CG rats (n = 23), the mean [Fe] values estimated by MRI and ICP-MS were 13.2 μmol·g−1 and 5.9 μmol·g−1, respectively, in the tumors, and 19.0μmol ·g−1 and 11.7 μmol·g−1, respectively, in the hepatic tissue. In the IG rats (n = 19), the values obtained by MRI and ICP-MS were 148.9 μmol·g−1 and 9.4 μmol · g−1, respectively, in the tumors, and 115.3 μmol·g−1 and 11.6 μmol·g−1, respectively, in the healthy liver tissue. The IG results revealed a clear disagreement between MRI and ICP-MS. In the comparative analysis between the groups regarding the [Fe] values obtained by ICP-MS, significant differences were found for the tumor samples (P < 0.001), but not for the hepatic tissue (P = 0.92). Under microscopy, scattered intravascular deposits of nanoparticles were observed, especially in the tumors. Conclusion ICP-MS demonstrated significant uptake of exogenous iron in tumor tissue. MRI was useful for quantifying the [Fe] in the different tissues in the CG animals, but not in the IG animals. Although the irregular distribution of nanoparticles caused an important bias in the measurements obtained by MRI, the relative increase in iron content inside the tumor was suggested. PMID:22661893

Cone Beam Computed Tomography (CBCT) in the Field of Interventional Oncology of the Liver

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

Bapst, Blanche, E-mail: blanchebapst@hotmail.com; Lagadec, Matthieu, E-mail: matthieu.lagadec@bjn.aphp.fr; Breguet, Romain, E-mail: romain.breguet@hcuge.ch

Cone beam computed tomography (CBCT) is an imaging modality that provides computed tomographic images using a rotational C-arm equipped with a flat panel detector as part of the Angiography suite. The aim of this technique is to provide additional information to conventional 2D imaging to improve the performance of interventional liver oncology procedures (intraarterial treatments such as chemoembolization or selective internal radiation therapy, and percutaneous tumor ablation). CBCT provides accurate tumor detection and targeting, periprocedural guidance, and post-procedural evaluation of treatment success. This technique can be performed during intraarterial or intravenous contrast agent administration with various acquisition protocols to highlightmore » liver tumors, liver vessels, or the liver parenchyma. The purpose of this review is to present an extensive overview of published data on CBCT in interventional oncology of the liver, for both percutaneous ablation and intraarterial procedures.« less

Antidiabetic drugs restore abnormal transport of amyloid-β across the blood-brain barrier and memory impairment in db/db mice.

PubMed

Chen, Fang; Dong, Rong Rong; Zhong, Kai Long; Ghosh, Arijit; Tang, Su Su; Long, Yan; Hu, Mei; Miao, Ming Xing; Liao, Jian Min; Sun, Hong Bing; Kong, Ling Yi; Hong, Hao

2016-02-01

Previous studies have shown significant changes in amyloid-β (Aβ) transport across the blood-brain barrier (BBB) under diabetic conditions with hypoinsulinemia, which is involved in diabetes-associated cognitive impairment. Present study employed db/db mice with hyperinsulinemia to investigate changes in Aβ transport across the BBB, hippocampal synaptic plasticity, and restorative effects of antidiabetic drugs. Our results showed that db/db mice exhibited similar changes in Aβ transport across the BBB to that of insulin-deficient mice. Chronic treatment of db/db mice with antidiabetic drugs such as metformin, glibenclamide and insulin glargine significantly decreased Aβ influx across the BBB determined by intra-arterial infusion of (125)I-Aβ(1-40), and expression of the receptor for advanced glycation end products (RAGE) participating in Aβ influx. Insulin glargine, but not, metformin or glibenclamide increased Aβ efflux across the BBB determined by stereotaxic intra-cerebral infusion of (125)I-Aβ(1-40), and expression of the low-density lipoprotein receptor related protein 1 (LRP1) participating in Aβ efflux. Moreover, treatment with these drugs significantly decreased hippocampal Aβ(1-40) or Aβ(1-42) and inhibited neuronal apoptosis. The drugs also ameliorated memory impairment confirmed by improved performance on behavioral tasks. However, insulin glargine or glibenclamide, but not metformin, restored hippocampal synaptic plasticity characterized by enhancing in vivo long-term potentiation (LTP). Further study found that these three drugs significantly restrained NF-κB, but only insulin glargine enhanced peroxisome proliferator-activated receptor γ (PPARγ) activity at the BBB in db/db mice. Our data indicate that the antidiabetic drugs can partially restore abnormal Aβ transport across the BBB and memory impairment under diabetic context. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Fryburg, D.A.; Barrett, E.J.; Louard, R.J.

To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using (3H)phenylalanine (Phe) and (14C)leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release ofmore » Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans (1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and (2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action.« less

Use of Intra-Arterial Chemotherapy and Embolization Before Limb Salvage Surgery for Osteosarcoma of the Lower Extremity

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

Zhang Huojun, E-mail: chyyzhj@hotmail.com; Yang Jijin, E-mail: yangjijin@live.com; Lu Jianping

We report our experience with the use of intra-arterial chemotherapy and embolization before limb salvage surgery in patients with osteosarcoma of the lower extremity. We evaluated the effect of this procedure on the degree of tumor necrosis and on the amount of blood loss during surgery. We reviewed the medical records of all patients who received intra-arterial chemotherapy and embolization before undergoing limb salvage surgery for osteosarcoma of the lower extremity at our institution between January 2003 and April 2008. Patient demographic, tumor characteristics, treatment details, postembolization complications, and surgical and pathological findings were recorded for each patient. We evaluatedmore » the operative time, estimated blood loss (EBL), and volume of blood transfusion during surgery and in the postoperative period in all patients in the study group. The same parameters were recorded for 65 other patients with lower extremity osteosarcoma who underwent limb salvage operation at our institution without undergoing preoperative intervention. The study included 47 patients (25 males and 22 females). Angiography showed that the tumors were hypervascular. Intra-arterial chemotherapy and embolization were performed successfully, resulting in a substantial reduction or complete disappearance of tumor stain in all patients. No major complications were encountered. At the time of surgery, performed 3-7 days after embolization, a fibrous edematous band around the tumor was observed in 43 of the 47 patients, facilitating surgery. The goal of limb salvage was achieved successfully in all cases. Percentage tumor necrosis induced by treatment ranged from 70.2% to 94.2% (average, 82.9%). EBL during surgery, EBL from drains in the postoperative period, total EBL, and transfusion volumes were significantly lower in the 47 study patients compared to the 65 patients who underwent surgery without preoperative treatment with intra-arterial chemotherapy and embolization. The mean operative time was also significantly less in the intervention group compared to the nonintervention group (73.2 vs. 88.5 min; p < 0.05). In conclusion, intra-arterial chemotherapy and embolization performed 3 to 7 days before limb salvage surgery in patients with lower extremity osteosarcomas can cause substantial tumor necrosis, reduce the EBL and transfusion requirements during surgery, and induce formation of a false capsule around the tumor, thus facilitating surgical excision of the tumors.« less

Pulmonary artery aneurysm and thrombosis in active tuberculous consolidation.

PubMed

Jemshad, A; Ahammed, Shameem; Abdulla, Mansoor C; Musambil, Mohthash

2015-07-01

Tuberculosis continues to remain challenging with a variety of complications. We report the case of a 58-year-old female who developed pulmonary artery aneurysm with intra-arterial thrombus as a complication of active tuberculosis. Even though there are reports of pulmonary artery aneurysm in tuberculous cavity, pulmonary artery aneurysm and intra-arterial thrombus in active tuberculosis are very rare. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Intra-arterial nitroglycerin for intra-operative arterial vasospasm during pediatric renal transplantation.

PubMed

Penna, Frank J; Harvey, Elizabeth; John, Philip; Armstrong, Derek; Luginbuehl, Igor; Odeh, Rakan I; Alyami, Fahad; Koyle, Martin A; Lorenzo, Armando J

2016-05-01

Intra-operative arterial vasospasm during pediatric renal transplantation is an urgent clinical situation resulting in end-organ ischemia, associated changes in parenchymal turgor and color, diminished flow on ultrasound, and if left untreated, allograft loss. We hypothesized that intra-operative intra-arterial injection of nitroglycerin would reverse vasospasm and improve renal perfusion. A three-yr-old girl with end-stage renal disease due to autosomal recessive polycystic kidney disease on peritoneal dialysis underwent deceased donor renal transplantation. After optimal immediate reperfusion and hemodynamic parameters, the kidney lost turgor and became mottled in appearance despite adequate hilar arterial and venous Doppler waveforms. Two aliquots of 40 μg (0.4 mL of a 100 μg/mL) nitroglycerin solution were injected directly into the renal artery 10 min apart. Nitroglycerin resulted in dramatic change in the consistency and appearance of the allograft. An improvement in renal blood flow was demonstrated by ultrasound after the second intra-arterial nitroglycerin injection with only a transient decrease in systemic arterial blood pressure. The child experienced normal allograft perfusion on serial postoperative ultrasounds, with a prompt decrease in serum creatinine and excellent diuresis. Intra-arterial nitroglycerin is a promising option for intra-operative arterial vasospasm during pediatric renal transplantation with objective improvement in blood flow and perfusion. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience.

PubMed

Gobin, Y Pierre; Dunkel, Ira J; Marr, Brian P; Brodie, Scott E; Abramson, David H

2011-06-01

To determine whether intra-arterial chemotherapy is safe and effective in advanced intraocular retinoblastoma. Retinoblastoma often presents with advanced intraocular disease and, despite conventional treatment with intravenous chemotherapy and external beam radiation therapy, may still require enucleation. Single-arm, prospective registry from May 30, 2006, to May 30, 2010, at an ophthalmic oncology referral center with ambulatory care. A total of 95 eyes of 78 patients with unilateral or bilateral retinoblastoma were treated. The intervention was selective catheterization of the ophthalmic artery and injection of chemotherapy, usually melphalan with or without topotecan. Drug dosage was determined by age and angioanatomy. The main outcome measures were procedural success, event-free (enucleation or radiotherapy) ocular survival, and ocular and extraocular complications. Catheterization succeeded in 98.5% of procedures. There were 289 chemotherapy injections (median, 3 per eye). The Kaplan-Meier estimates of ocular event-free survival rates at 2 years were 70.0% (95% confidence interval, 57.9%-82.2%) for all eyes, 81.7% (95% confidence interval, 66.8%-96.6%) for eyes that received intra-arterial chemotherapy as primary treatment, and 58.4% (95% confidence interval, 39.5%-77.2%) for eyes that had previous treatment failure with intravenous chemotherapy and/or external beam radiation therapy. There were no permanent extraocular complications. Our experience suggests that intra-arterial chemotherapy is safe and effective in the treatment of advanced intraocular retinoblastoma.

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

PubMed Central

Uka, Kiminori; Aikata, Hiroshi; Takaki, Shintaro; Kawaoka, Tomokazu; Saneto, Hiromi; Miki, Daiki; Takahashi, Shoichi; Toyota, Naoyuki; Ito, Katsuhide; Chayama, Kazuaki

2008-01-01

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC). Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP). Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients), and progressive disease (no patients). The median survival period was 8 mo (range, 5-55). With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%), seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non-resectable advanced HCC, but it has severe hematologic toxicity. PMID:18442216

Liver metastases from colorectal cancer: regional intra-arterial treatment following failure of systemic chemotherapy

PubMed Central

Cyjon, A; Neuman-Levin, M; Rakowsky, E; Greif, F; Belinky, A; Atar, E; Hardoff, R; Brenner, B; Sulkes, A

2001-01-01

This study was designed to determine response rate, survival and toxicity associated with combination chemotherapy delivered intra-arterially to liver in patients with hepatic metastases of colorectal origin refractory to standard systemic treatment. A total of 28 patients who failed prior systemic treatment with fluoropyrimidines received a median of 5 cycles of intra-arterial treatment consisting of 5-fluorouracil 700 mg/m2/d, leucovorin 120 mg/m2/d, and cisplatin 20 mg/m2/d for 5 consecutive days. Cycles were repeated at intervals of 5–6 weeks. A major response was achieved in 48% of patients: complete response in 8% and partial response in 40%. The median duration of response was 11.5 months. Median survival was 12 months at a median follow up of 12 months. On multivariate analysis, the only variables with a significant impact on survival were response to treatment and performance status. Toxicity was moderate: grades III–IV neutropenia occurred in 29% of patients. Most of the patients complained of fatigue lasting for a few days following each cycle. There were no cases of hepatobiliary toxicity. These findings indicate that regional intra-arterial treatment should be considered in selected patients with predominantly liver disease following failure of standard treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11506487

Disposition of epirubicin after intraarterial administration in Lipiodol to patients with hepatocellular carcinoma.

PubMed

Dodds, H M; Walpole, E T; Rivory, L P; Strong, R W; Pond, S M

1996-10-01

Delivering emulsions of anthracycline drugs in Lipiodol, an iodinated poppy-seed oil, via the hepatic artery for the treatment of hepatocellular carcinoma (HCC) has become increasingly popular. However, investigations to determine the extent to which the Lipiodol sequesters the anthracycline in the liver have been limited. Concern has been expressed that such emulsions are not stable and that the anthracycline is, therefore, released rapidly into the circulation. We studied the pharmacokinetics of epirubicin (50 mg m-2) in five patients with nonresectable primary hepatocellular carcinoma after infusion of an epirubicin/Lipiodol emulsion via the hepatic artery. We used a reliable and specific high-performance liquid chromatography assay that allows quantitation of plasma concentrations of epirubicin, epirubicinol, epirubicin glucuronide, and epirubicin aglycone. Although a large interpatient variability in pharmacokinetics was observed, our results were similar to historical data after epirubicin intravenous therapy. Only the results from one patient provided evidence of significant retention of the drug in the liver. It would appear that more stable formulations of epirubicin/Lipiodol are required to increase the efficacy of this form of treatment. We suggest that pharmacokinetic studies should accompany clinical evaluation of emulsions of epirubicin/Lipiodol for the treatment of HCC.

Intra-arterial intervention chemotherapy for sarcoma and cancerous ulcer via an implanted pump.

PubMed

Liu, Cheng; Cui, Qiu; Guo, Jun; Li, Dingfeng; Zeng, Yanjun

2014-04-01

To observe the efficacy of intra-arterial chemotherapy with subcutaneously implanted pump for soft tissue sarcoma in extremities and cancerous ulcer. 31 patients with ulcerative skin squamous cell carcinoma or sarcoma in extremities who received treatment during the period from July 2003 to November 2011 at our hospital were recruited, including 15 male and 16 female patients, aging between 14 and 83 with average age of 49 years old. 10 patients had tumor in upper extremities and 21 patients in lower extremities. The pathological types of studied cases include 9 cases with skin squamous cell carcinoma, 6 cases with synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of cancerous ulcer were pain, infection and hemorrhage; All the studied patients were administrated with cisplatin and doxorubicin by intra-arterial chemotherapy pump, and the patients with squamous cell carcinoma were additionally applied with bleomycin and patients with malignant melanoma were additionally applied with dacarbazine. The chemotherapy efficiency was observed after at 3 cycles of intra-arterial chemotherapy. The total remission rate of pain (RR) was 87 %, and total remission rate of ulcer cicatrization (RR) was 71 %, with ulcer cicatrizing spontaneously in 9 cases and obvious homeostasis in 5 cases with bleeding ulcers. 19 patients underwent surgery after chemotherapy, in which 16 cases had limb-salvage surgery and 3 cases underwent lower leg amputation after chemotherapy, and 3 patients out of 16 cases had local recurrence (19 %). The subcutaneous intra-arterial targeting chemotherapy could be applied to treat refractory sarcoma and cancerous ulcer in extremities to significantly increase the chemotherapeutic concentration at tumor area so as to effectively constrain the tumor rupture induced main symptoms including pain, infection and bleeding, which would help to make a decreased blood supplied and well defined tumor boundary to finally decrease the recurrence rate.

Safety and Efficiency of Low Dose Intra-arterial Tirofiban in Mechanical Thrombectomy During Acute Ischemic Stroke.

PubMed

Yu, Tongya; Lin, Yingying; Jin, Aiping; Zhang, Pei; Zhou, Xiaoyu; Fang, Min; Liu, Xueyuan

2018-06-04

In this study, we aimed to evaluate the safety and efficiency of low dose intra-arterial tirofiban in mechanical thrombectomy of acute ischemic stroke patients to facilitate the reperfusion of distal vessel. We retrospectively analyzed 54 consecutive acute ischemic patients who underwent mechanical thrombectomy for large-vessel occlusion. Patients were divided into two groups based on whether intra-arterial tirofiban was used during mechanical thrombectomy to facilitate the reperfusion of distal vessel. Patients in Non-tirofiban group (n=28) have received mechanical thrombectomy, while Patients in Tirofiban group (n=26) have received mechanical thrombectomy with a low dose intra-arterial tirofiban. We comparatively analyzed two groups of the bleeding complications, recanalization rate, 24-hour National Institutes of Health Stroke Scale score, functional independence of 90 day and mortality rate. Of 54 patients undergoing mechanical thrombectomy, baseline characteristics did not differ between the Tirofiban group and Non-tirofiban cohort. Symptomatic intracranial hemorrhage rates were not different between Tirofiban group and Non-tirofiban group (11.5 % vs. 14.3%). Total 47 (87.0%) patients have realized successful recanalization, no apparent difference between two groups (85.7% vs 88.5%, P>0.05). Mean 24-hour National Institutes of Health Stroke Scale score was 9.24±6.85, 9.11±8.13 in the Non-tirofiban group and 9.39±5.31 in the Tirofiban group respectively, P>0.05. Total 20 (35.7%) patients have achieved functional independence (34.6% vs 39.3%, P>0.05) at 90 days. Patients treated with tirofiban presented lower mortality when compared with those who were not treated with tirofiban without significant difference (10.7% versus 3.8%, P>0.05). Intra-arterial tirofiban may be safe in mechanical thrombectomy of acute ischemic stroke to facilitate the reperfusion of distal vessel, but has no beneficial effect on prognosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Liu, Fenghua; Tang, Yong; Sun, Junwei; Yuan, Zhanna; Li, Shasha; Sheng, Jun; Ren, He; Hao, Jihui

2012-01-01

To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC) versus systemic chemotherapy for stage III/IV pancreatic cancer. Randomized controlled trials of patients with advanced pancreatic cancer treated by regional intra-arterial or systemic chemotherapy were identified using PubMed, ISI, EMBASE, Cochrane Library, Google, Chinese Scientific Journals Database (VIP), and China National Knowledge Infrastructure (CNKI) electronic databases, for all publications dated between 1960 and December 31, 2010. Data was independently extracted by two reviewers. Odds ratios and relative risks were pooled using either fixed- or random-effects models, depending on I(2) statistic and Q test assessments of heterogeneity. Statistical analysis was performed using RevMan 5.0. Six randomized controlled trials comprised of 298 patients met the standards for inclusion in the meta-analysis, among 492 articles that were identified. Eight patients achieved complete remission (CR) with regional intra-arterial chemotherapy (RIAC), whereas no patients achieved CR with systemic chemotherapy. Compared with systemic chemotherapy, patients receiving RIAC had superior partial remissions (RR = 1.99, 95% CI: 1.50, 2.65; 58.06% with RIAC and 29.37% with systemic treatment), clinical benefits (RR = 2.34, 95% CI: 1.84, 2.97; 78.06% with RAIC and 29.37% with systemic treatment), total complication rates (RR = 0.72, 95% CI: 0.60, 0.87; 49.03% with RIAC and 71.33% with systemic treatment), and hematological side effects (RR = 0.76, 95% CI: 0.63, 0.91; 60.87% with RIAC and 85.71% with systemic treatment). The median survival time with RIAC (5-21 months) was longer than for systemic chemotherapy (2.7-14 months). Similarly, one year survival rates with RIAC (28.6%-41.2%) were higher than with systemic chemotherapy (0%-12.9%.). Regional intra-arterial chemotherapy is more effective and has fewer complications than systemic chemotherapy for treating advanced pancreatic cancer.

Comparison of phase-contrast MR imaging and endovascular sonography for intracranial blood flow velocity measurements.

PubMed

Schneiders, J J; Ferns, S P; van Ooij, P; Siebes, M; Nederveen, A J; van den Berg, R; van Lieshout, J; Jansen, G; vanBavel, E; Majoie, C B

2012-10-01

Local hemodynamic information may help to stratify rupture risk of cerebral aneurysms. Patient-specific modeling of cerebral hemodynamics requires accurate data on BFV in perianeurysmal arteries as boundary conditions for CFD. The aim was to compare the BFV measured with PC-MR imaging with that obtained by using intra-arterial Doppler sonography and to determine interpatient variation in intracranial BFV. In 10 patients with unruptured intracranial aneurysms, BFV was measured in the cavernous ICA with PC-MR imaging in conscious patients before treatment, and measured by using an intra-arterial Doppler sonography wire when the patient was anesthetized with either propofol (6 patients) or sevoflurane (4 patients). Both techniques identified a pulsatile blood flow pattern in cerebral arteries. PSV differed >50 cm/s between patients. A mean velocity of 41.3 cm/s (95% CI, 39.3-43.3) was measured with PC-MR imaging. With intra-arterial Doppler sonography, a mean velocity of 29.3 cm/s (95% CI, 25.8-32.8) was measured with the patient under propofol-based intravenous anesthesia. In patients under sevoflurane-based inhaled anesthesia, a mean velocity of 44.9 cm/s (95% CI, 40.6-49.3) was measured. We showed large differences in BFV between patients, emphasizing the importance of using patient-specific hemodynamic boundary conditions in CFD. PC-MR imaging measurements of BFV in conscious patients were comparable with those obtained with the intra-arterial Doppler sonography when the patient was anesthetized with a sevoflurane-based inhaled anesthetic.

Feasibility and safety of transfemoral intra-arterial chemotherapy for head and neck cancer using a 3-French catheter system: comparison with a 4-French catheter system.

PubMed

Watanabe, Shigeru; Yamamoto, Akira; Torigoe, Teruyuki; Kanki, Akihiko; Tamada, Tsutomu; Ito, Katsuyoshi

2016-02-01

To assess the technical feasibility of transfemoral intra-arterial chemotherapy for head and neck cancer using a 3-French catheter system (3-Fr). Sixty-two patients with head and neck cancer who underwent transfemoral intra-arterial chemotherapy were included in this study. Thirty-three patients underwent treatment using a 3-Fr (group 3-Fr). Twenty-nine patients underwent treatment using a 4-French catheter system (group 4-Fr). The technical success rate, duration of the procedure with fluoroscopy, and rate of procedure-related complications were compared between group 3-Fr and group 4-Fr. In addition, in group 3-Fr, bleeding at the puncture site after 1.5 h of bed rest was evaluated. The technical success rate was 100% in both groups. The duration of the procedure with fluoroscopy didn't differ between group 3-Fr (mean 28.0 min) and group 4-Fr (mean 30.2 min) (p = 0.524). There was no procedure-related complication in either group. In group 3-Fr, no hemorrhagic complication was observed. A 3-French catheter system can be used to perform transfemoral intra-arterial chemotherapy for head and neck cancer and is technically feasible with approximately the same duration of the procedure with fluoroscopy. Furthermore, this method may shorten the bed rest time without hemorrhagic complication, and may reduce the risk of pulmonary embolism.

Coils versus gelatin particles with or without intraarterial antibiotics for partial splenic embolization: a comparative evaluation.

PubMed

Masada, Tetsuya; Tanaka, Toshihiro; Sakaguchi, Hiroshi; Nakagomi, Masahiro; Miura, Yuko; Hidaka, Teruyuki; Sato, Yozo; Sato, Takeshi; Inoue, Masayoshi; Furuich, Kinya; Nishiofuku, Hideyuki; Kichikawa, Kimihiko

2014-06-01

To compare the efficacy, complications, and inflammatory levels in partial splenic embolization (PSE) with coils or gelatin sponge (GS) particles with or without intraarterial antibiotic agents. Forty-four patients with hypersplenism treated by PSE were assessed. GS particles were used in 31 patients, and coils were used in 13 patients. In 17 of the 31 patients who received GS, GS suspended in antibiotic solution was injected via the splenic artery. In the other 14 patients, antibiotic agents were not used. In all 13 coil group patients, an antibiotic solution was intraarterially injected before embolization. Platelet counts were compared between the GS and coil groups. Complications and serum C-reactive protein (CRP) levels were compared among the three groups. There were no significant differences in platelet counts and platelet increased ratios at 6 months (10.0 × 10(4)/µL and 193% in the GS group vs 9.0 × 10(4)/µL and 221% in the coil group), and no significant differences in frequencies of complications. However, one splenic abscess occurred in a patient treated with GS without antibiotics, resulting in death. The mean serum CRP level in the GS with antibiotic group at 2 weeks was significantly lower than in the other two groups. The efficacy of PSE is similar with the use of coils versus GS particles. Prophylactic intraarterial antibiotic treatment could be useful in preventing inflammatory reactions after PSE. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study.

PubMed

Hancı, Volkan; Özbilgin, Şule; Özbal, Seda; Kamacı, Gonca; Ateş, Hasan; Boztaş, Nilay; Ergür, Bekir Uğur; Arıkanoğlu, Ahmet; Yılmaz, Osman; Yurtlu, Bülent Serhan

2016-01-01

Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1μg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p<0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study].

PubMed

Hancı, Volkan; Özbilgin, Şule; Özbal, Seda; Kamacı, Gonca; Ateş, Hasan; Boztaş, Nilay; Ergür, Bekir Uğur; Arıkanoğlu, Ahmet; Yılmaz, Osman; Yurtlu, Bülent Serhan

2016-01-01

Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1μg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p<0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

I.v. and intraarterial hybrid digital subtraction angiography: clinical evaluation.

PubMed

Foley, W D; Beres, J; Smith, D F; Bell, R M; Milde, M W; Lipchik, E O

1986-09-01

Temporal/energy (hybrid) subtraction is a technique for removing soft-tissue motion artifact from digital subtraction angiograms. The diagnostic utility of hybrid subtraction for i.v. and intraarterial angiography was assessed in the first 9 months of operation of a dedicated production system. In i.v. carotid arteriography (N = 127), hybrid subtraction (H) provided a double-profile projection of the carotid bifurcation in an additional 14% of studies, compared with temporal subtraction (T) alone (H79:T48, p less than 0.001). However, a change in estimated percent stenosis or additional diagnostic information occurred in only 2% of studies. In i.v. abdominal arteriography (N = 23), hybrid subtraction, compared with temporal subtraction, provided a diagnostic examination in an additional 14% of studies (H20:T17); however, this difference is not statistically significant. An additional three i.v. abdominal angiograms were nondiagnostic. In intraarterial abdominal (N = 98) and pelvic (N = 60) angiography, hybrid subtraction provided a diagnostic examination in an additional 5% of studies (abdomen H94:T90, pelvis H58:T56); this difference was not statistically significant. An additional 5% of all intraarterial abdominal and pelvic digital subtraction angiographic studies were considered nondiagnostic. Hybrid subtraction provides a double-profile view of the carotid bifurcation in a significant number of patients. However, apart from some potential for improved i.v. abdominal arteriography, hybrid subtraction does not result in significant improvement in comparison to conventional temporal-subtraction techniques.

Intra-Arterial Drug and Light Delivery for Photodynamic Therapy Using Visudyne®: Implication for Atherosclerotic Plaque Treatment.

PubMed

Jain, Manish; Zellweger, Matthieu; Frobert, Aurélien; Valentin, Jérémy; van den Bergh, Hubert; Wagnières, Georges; Cook, Stéphane; Giraud, Marie-Noelle

2016-01-01

Photodynamic therapy (PDT), which is based on the activation of photosensitizers with light, can be used to reduce plaque burden. We hypothesized that intra-arterial photosensitizer administration and photo-activation will lead to high and rapid accumulation within the plaque with reduced systemic adverse effects. Thus, this "intra-arterial" PDT would be expected to have less side effects and due to the short time involved would be compatible with percutaneous coronary interventions. We characterized the dose-dependent uptake and efficacy of intra-arterial PDT using Liposomal Verteporfin (Visudyne®), efficient for cancer-PDT but not tested before for PDT of atherosclerosis. Visudyne® (100, 200, and 500 ng/ml) was perfused for 5-30 min in atherosclerotic aorta isolated from ApoE(-/-) mice. The fluorescence Intensity (FI) after 15 min of Visudyne® perfusion increased with doses of 100 (FI-5.5 ± 1.8), 200 (FI-31.9 ± 1.9) or 500 ng/ml (FI-42.9 ± 1.2). Visudyne® (500 ng/ml) uptake also increased with the administration time from 5 min (FI-9.8 ± 2.5) to 10 min (FI-23.3 ± 3.0) and 15 min (FI-42.9 ± 3.4) before reaching saturation at 30 min (FI-39.3 ± 2.4) contact. Intra-arterial PDT (Fluence: 100 and 200 J/cm(2), irradiance-334 mW/cm(2)) was applied immediately after Visudyne® perfusion (500 ng/ml for 15 min) using a cylindrical light diffuser coupled to a diode laser (690 nm). PDT led to an increase of ROS (Dihydroethidium; FI-6.9 ± 1.8, 25.3 ± 5.5, 43.4 ± 13.9) and apoptotic cells (TUNEL; 2.5 ± 1.6, 41.3 ± 15.3, 58.9 ± 6%), mainly plaque macrophages (immunostaining; 0.3 ± 0.2, 37.6 ± 6.4, 45.3 ± 5.4%) respectively without laser irradiation, or at 100 and 200 J/cm(2). Limited apoptosis was observed in the medial wall (0.5 ± 0.2, 8.5 ± 4.7, 15.3 ± 12.7%). Finally, Visudyne®-PDT was found to be associated with reduced vessel functionality (Myogram). We demonstrated that sufficient accumulation of Visudyne® within plaque could be achieved in short-time and therefore validated the feasibility of local intravascular administration of photosensitizer. Intra-arterial Visudyne®-PDT preferentially affected plaque macrophages and may therefore alter the dynamic progression of plaque development.

Repeated combined endovascular therapy with milrinone and nimodipine for the treatment of severe vasospasm: preliminary results.

PubMed

Sherif, Camillo; Wambacher, Bernhard; Loyoddin, Michel; Karaic, Radenko; Krafft, Peter; Valentin, Andreas; Tscholakoff, Dimiter; Kleinpeter, Guenther

2015-01-01

Delayed vasospasm (VSP) following aneurysmal subarachnoid hemorrhage (aSAH) remains a major source of morbidity. Milrinone was recently suggested as an invasive VSP treatment option. It is a phosphodiesterase III inhibitor with vasodilating and additional positive inotrope and anti-inflammatory effects. In this preliminary series, we included patients with severe VSP and unsuccessful maximum conservative therapy. Inclusion criteria were (1) transcranial Doppler (TCD) mean >180 cm/s; (2) increase of >50 % of TCD mean values within 6 h to values >150 cm/s; and/or (3) neurological deterioration (after exclusion of hemorrhage, hydrocephalus, and other systemic reasons). Patients received endovascular therapy with nimodipine 2 mg followed by milrinone 4-8 mg. Reinterventions were indicated aggressively in cases of persistent neurological deficits or persistent high mean TCD >180 cm/s. Of 121 consecutive aSAH patients, 16 (13.2 %) received endovascular VSP therapy. Of these, 11 patients (68.5 %) received ≥ 3 interventions (median 4; maximum 9); 14 (87.5 %) showed postinterventional angiographic improvement of vessel diameters; and 11 (68.5 %) showed improvement of their neurological deficits after a mean follow-up time of 4.5 months. No cardiovascular adverse events attributed to milrinone were observed. Milrinone may be a useful supplementary substance for endovascular VSP therapy. Aggressive reintervention indications did not cause additional adverse events.

Nimodipine nanocrystals for oral bioavailability improvement: preparation, characterization and pharmacokinetic studies.

PubMed

Fu, Qiang; Sun, Jin; Zhang, Dong; Li, Mo; Wang, Yongjun; Ling, Guixia; Liu, Xiaohong; Sun, Yinghua; Sui, Xiaofan; Luo, Cong; Sun, Le; Han, Xiaopeng; Lian, He; Zhu, Meng; Wang, Siling; He, Zhonggui

2013-09-01

This study intended to develop nimodipine (NMD) nanocrystals with different sizes for oral administration and to investigate the relationship between dissolution and pharmacokinetics for NMD nanocrystals and Nimotop(®). NMD nanocrystals were prepared by combination of microprecipitation and high pressure homogenization and were further lyophilized. The particle size, morphology and aqueous solubility of the NMD nanocrystals were determined. With Nimotop(®) as the control, the dissolution rate was evaluated and the pharmacokinetic study was undertaken in beagle dogs. NMD nanocrystals with mean diameters of about 159.0, 503.0 and 833.3 nm were prepared, respectively. The lyophilization didn't affect the particle sizes of the redispersed nanocrystals. The aqueous solubility was significantly improved and displayed a size-dependent manner. The nanocrystals exhibited lower dissolution patterns than Nimotop(®) under non-sink condition, but bioavailability of the two nanocrystals (159.0 and 833.3 nm) was equivalent, about 2.6-fold higher than Nimotop(®). In conclusion, oral nanocrystal drug delivery system was a promising strategy in improving the oral bioavailability of poorly soluble or insoluble drugs. But we could not establish a favorable in vitro in vivo correlation for NMD nanocrystals and Nimotop(®) and thus the oral absorption mechanism of the NMD nanocrystals required further study. Copyright © 2013 Elsevier B.V. All rights reserved.

Scintigraphic Tracking of Allogeneic Mesenchymal Stem Cells in the Distal Limb After Intra-Arterial Injection in Standing Horses.

PubMed

Espinosa, Pablo; Spriet, Mathieu; Sole, Albert; Walker, Naomi J; Vaughan, Betsy; Galuppo, Larry D

2016-07-01

To assess the feasibility of intra-arterial administration of allogeneic mesenchymal stem cells (MSC) in the median artery of standing horses and evaluate the distribution and retention of radiolabeled cells. In vivo experimental study. Six research horses. Technetium(99m) -HexaMethyl-Propylene-Amine Oxime-labeled MSC were injected under ultrasound guidance in the median artery of 6 front limbs of 3 horses, standing under sedation. Scintigraphic images were obtained at the time of injection, and at 1, 6, and 24 hours postinjection. Six additional limbs from 3 horses were similarly injected with unlabeled MSC. Ultrasound was performed the following day for assessment of vascular changes. Intra-arterial injection was performed successfully in 11 of 12 limbs. In 1 limb, partial periarterial injection compromised the success of the procedure. Homogeneous distribution of radiolabeled MSC was observed through the entire distal limb, including within the hoof. Partial venous thrombosis was found in both groups of horses, but was subjectively less severe in horses injected with unlabeled MSC. No lameness was observed. Transient swelling of the distal limb occurred in only 1 limb. Intra-arterial injection of MSC can be performed in standing horses under sedation and successfully distribute MSC to the distal limb. A risk of periarterial injection was identified but can be reduced with proper sedation, local anesthesia, and increased experience. Partial venous thrombosis was observed as a complication, but did not cause changes of clinical importance, other than rare transient swelling. © Copyright 2016 by The American College of Veterinary Surgeons.

Intraarterial Liver-Directed Therapies: The Role of Interventional Oncology

PubMed Central

Ma, Jenson; Sandow, Tyler; Devun, Daniel; Kirsch, David; Gulotta, Paul; Gilbert, Patrick; Kay, Dennis

2017-01-01

Background: Since the early 1990s, the minimally invasive image-guided therapies used in interventional oncology to treat hepatocellular carcinoma have continued to evolve. Additionally, the range of applications has been expanded to the treatment of hepatic metastases from colorectal cancer, neuroendocrine tumors, cholangiocarcinoma, breast cancer, melanoma, and sarcoma. Methods: We searched the literature to identify publications from 1990 to the present on various image-guided intraarterial therapies and their efficacy, as well as their role in the management of primary and secondary liver malignancies. Results: Chemoembolization and radioembolization are considered a standard of care in treating, delaying progression of disease, and downstaging to bridge to liver transplantation. Progression-free survival and overall survival outcomes are promising in patients with colorectal cancer and neuroendocrine tumors with liver metastases. Applications in the treatment of hepatic metastases from cholangiocarcinoma, breast cancer, melanoma, and sarcoma also show potential. Conclusion: Interventional oncology and its image-guided intraarterial therapies continue to gain recognition as treatment options for primary and secondary liver cancers. Growing evidence supports their role as a standard of care alongside medical oncology, surgery, and radiation oncology. PMID:29230127

Cationizable lipid micelles as vehicles for intraarterial glioma treatment.

PubMed

Nguyen, Juliane; Cooke, Johann R N; Ellis, Jason A; Deci, Michael; Emala, Charles W; Bruce, Jeffrey N; Bigio, Irving J; Straubinger, Robert M; Joshi, Shailendra

2016-05-01

The relative abundance of anionic lipids on the surface of endothelia and on glioma cells suggests a workable strategy for selective drug delivery by utilizing cationic nanoparticles. Furthermore, the extracellular pH of gliomas is relatively acidic suggesting that tumor selectivity could be further enhanced if nanoparticles can be designed to cationize in such an environment. With these motivating hypotheses the objective of this study was to determine whether nanoparticulate (20 nm) micelles could be designed to improve their deposition within gliomas in an animal model. To test this, we performed intra-arterial injection of micelles labeled with an optically quantifiable dye. We observed significantly greater deposition (end-tissue concentration) of cationizable micelles as compared to non-ionizable micelles in the ipsilateral hemisphere of normal brains. More importantly, we noted enhanced deposition of cationizable as compared to non-ionizable micelles in glioma tissue as judged by semiquantitative fluorescence analysis. Micelles were generally able to penetrate to the core of the gliomas tested. Thus we conclude that cationizable micelles may be constructed as vehicles for facilitating glioma-selective delivery of compounds after intraarterial injection.

Successful Recanalization of Acute Superior Mesenteric Artery Thromboembolic Occlusion by a Combination of Intraarterial Thrombolysis and Mechanical Thrombectomy with a Carotid Filter

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

Zelenak, Kamil, E-mail: zelenak@unm.sk; Sinak, Igor; Janik, Jan

2013-06-15

Acute superior mesenteric artery (SMA) occlusion is a life-threatening disease, and acute intestinal ischemia develops from the sudden decrease in perfusion to the intestines. The key to saving the patient's life is early diagnosis, and prompt revascularization of the SMA can prevent intestinal infarction and decrease the risk of bowel segment necrosis. Computed tomographic angiography may be useful for rapid diagnosis. We report recanalization of an SMA occlusion in an 80-year-old man with a combination of intraarterial thrombolysis and mechanical thrombectomy with a carotid filter.

Differential effects of pyrethroid insecticides on extracellular dopamine in the striatum of freely moving rats

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

Mubarak Hossain, Muhammad; Suzuki, Tadahiko; United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193

2006-11-15

In order to obtain a more complete understanding of pyrethroid neurotoxicity, effects of the pyrethroid insecticides, allethrin (type I), cyhalothrin (type II) and deltamethrin (type II) on extracellular levels of dopamine (DA) and its metabolites in the striatum of conscious rats were studied by in vivo microdialysis. Rats were treated i.p. with pyrethroids or vehicle. Allethrin had a dual effect on DA release. The increase in the extracellular level of striatal DA by 10 mg/kg allethrin reached a maximum of 178% of baseline but 20 and 60 mg/kg inhibited DA release to 63% and 52% of baseline with a peakmore » effect at 60-80 min after injection. Cyhalothrin 10, 20 and 60 mg/kg inhibited DA release to 65%, 56% and 45% of basal release, respectively, with a peak time of inhibition 40-80 min past injection. Deltamethrin (10 and 20 mg/kg) increased DA release to maximum of 187% and 252% of basal release whereas 60 mg/kg first reduced the efflux for 40 min to 50% of basal release and then increased the efflux to a maximum of 344% of basal release with a peak time of 120 min. Local infusion of 1 {mu}M tetrodotoxin, a Na{sup +} blocker through the dialysis probe completely prevented the effect of allethrin (10 and 60 mg/kg), cyhalothrin (60 mg/kg) and deltamethrin (20 mg/kg) on DA release but only partially blocked the effects of 60 mg/kg deltamethrin. The effect of deltamethrin (60 mg/kg) on DA release was completely prevented by local infusion of 10 {mu}M nimodipine, an L-type Ca{sup ++} channel blocker. All three pyrethroids did not alter the extracellular levels of DOPAC, 3-MT and HVA except that 20 and 60 mg/kg of allethrin and cyhalothrin increased 3-MT levels. Effect of the pyrethroids on synaptosomal DA uptake was also examined. The DA uptake was decreased in rats exposed to 60 mg/kg of allethrin and cyhalothrin but was increased in rats exposed to 60 mg/kg of deltamethrin. Our results demonstrate that striatal DA release and DA uptake are differentially affected by type I and the two type II pyrethroids indicating that dopaminergic circuitry, striatal DA in particular, may be a pyrethroid target and that pyrethroids may be acting on striatal DA by multiple mechanisms.« less

Comparing Intra-Arterial Chemotherapy Combined With Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone: A Randomised Prospective Pilot Study for T1G3 Bladder Transitional Cell Carcinoma After Bladder-Preserving Surgery

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

Chen, Junxing, E-mail: Junxingchen@hotmail.com; Yao, Zhijun, E-mail: yaozhijun1985@qq.com; Qiu, Shaopeng, E-mail: qiushp@mail.sysu.edu.cn

Purpose: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Materials and Methods: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m{sup 2}) + cisplatin (60 mg/m{sup 2}) chemotherapy 2-3more » weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m{sup 2}) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. Results: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4 of 31) in groups A and B, respectively. During the intra-arterial chemotherapy cycle, although more than 50 % patients experienced some toxicities, most were minor and reversible [grade 1-2 (46.7 %) vs. grade 1-2 (6.9 %)]. Conclusion: These findings suggest that combining intra-arterial chemotherapy with intravesical chemotherapy could delay tumour recurrence and progression compared with intravesical chemotherapy alone and this type treatment is relatively safe.« less

Initiation of phase III contractions in the jejunum by atropine, hexamethonium and xylocaine in conscious dogs.

PubMed

Tohara, K; Uchida, Y; Suzuki, H; Itoh, Z

2000-02-01

Mechanisms of initiation of phase III contractions in the jejunum during the digestive state are not well understood. To test whether phase III can be induced by a local injection of various agents in a jejunal segment, a polyethylene tube was chronically placed in a branch of the jejunal artery, and force transducers were chronically placed in the upper jejunum. Local injection of atropine, hexamethonium and xylocaine induced caudal-migrating phase III in the injected segment only in the digestive state, and simultaneous intra-arterial infusions of L-arginine, an NK-1 antagonist, or 5-hydroxytryptamine (5-HT) 1P and 3 antagonists inhibited the induced phase III. Intravenous atropine and hexamethonium also inhibited xylocaine-induced phase III contractions. Atropine and hexamethonium-induced phase III were brought about by inhibition of neural transmission at nicotinic receptors in the inhibitory pathway to NO neurones. NK-1, 5-HT1P and 5-HT3 receptors are present in the excitatory but not the inhibitory pathway to NO neurones. Xylocaine appears to stop neuronal transmission from mechanoreceptors to NO neurones. Thus, the initiation of spontaneous occurrence of phase III in the digestive jejunum is likely to be brought about by transient cessation of postprandial contractions in a segment of the jejunum.

Modulation of postjunctional α-adrenergic vasoconstriction during exercise and exogenous ATP infusions in ageing humans

PubMed Central

Kirby, Brett S; Crecelius, Anne R; Voyles, Wyatt F; Dinenno, Frank A

2011-01-01

Abstract The ability to modulate sympathetic α-adrenergic vasoconstriction in contracting muscle is impaired with age. In young adults, adenosine triphosphate (ATP) has been shown to blunt sympathetic vasoconstrictor responsiveness similar to exercise. Therefore, we tested the hypothesis that modulation of postjunctional α-adrenergic vasoconstriction to exogenous ATP is impaired in ageing humans. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) to intra-arterial infusions of phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) during rhythmic handgrip exercise (15% MVC), a control non-exercise vasodilator condition (adenosine), and ATP infusion in seven older (64 ± 3 years) and seven young (22 ± 1 years) healthy adults. Forearm hyperaemia was matched across all vasodilatating conditions. During adenosine, forearm vasoconstrictor responses to direct α1-stimulation were lower in older compared with young adults (ΔFVC =−25 ± 3%vs.−41 ± 5%; P < 0.05), whereas the responses to α2-stimulation were not different (−35 ± 6%vs.−44 ± 8%; NS). During exercise, α1-mediated vasoconstriction was significantly blunted compared with adenosine in both young (−9 ± 2%vs.−41 ± 5%) and older adults (−15 ± 2%vs.−25 ± 3%); however, the magnitude of sympatholysis was reduced in older adults (32 ± 13 vs. 74 ± 8%; P < 0.05). Similarly, α2-mediated vasoconstriction during exercise was significantly blunted in both young (−15 ± 4%vs.−44 ± 8%) and older adults (−26 ± 3%vs.−35 ± 6%), however the magnitude of sympatholysis was reduced in older adults (19 ± 8%vs. 60 ± 10%; P < 0.05). During ATP, both α1- and α2-mediated vasoconstriction was nearly abolished in young and older adults (ΔFVC ∼−5%), and the magnitude of sympatholysis was similar in both age groups (∼85–90%). Our findings indicate that the ability to modulate postjunctional α-adrenergic vasoconstriction during exercise is impaired with age, whereas the sympatholytic effect of exogenous ATP is preserved. Thus, if impairments in vascular control during exercise in older adults involve vasoactive ATP, we speculate that circulating ATP is reduced with advancing age. PMID:21486772

Synthesis and evaluation of mesoporous carbon/lipid bilayer nanocomposites for improved oral delivery of the poorly water-soluble drug, nimodipine.

PubMed

Zhang, Yanzhuo; Zhao, Qinfu; Zhu, Wufu; Zhang, Lihua; Han, Jin; Lin, Qisi; Ai, Fengwei

2015-07-01

A novel mesoporous carbon/lipid bilayer nanocomposite (MCLN) with a core-shell structure was synthesized and characterized as an oral drug delivery system for poorly water-soluble drugs. The objective of this study was to investigate the potential of MCLN-based formulation to modulate the in vitro release and in vivo absorption of a model drug, nimodipine (NIM). NIM-loaded MCLN was prepared by a procedure involving a combination of thin-film hydration and lyophilization. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area analysis, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were employed to characterize the NIM-loaded MCLN formulation. The effect of MCLN on cell viability was assessed using the MTT assay. In addition, the oral bioavailability of NIM-loaded MCLN in beagle dogs was compared with that of the immediate-release formulation, Nimotop®. Our results demonstrate that the NIM-loaded MCLN formulation exhibited a typical sustained release pattern. The NIM-loaded MCLN formulation achieved a greater degree of absorption and longer lasting plasma drug levels compared with the commercial formulation. The relative bioavailability of NIM for NIM-loaded MCLN was 214%. MCLN exhibited negligible toxicity. The data reported herein suggest that the MCLN matrix is a promising carrier for controlling the drug release rate and improving the oral absorption of poorly water-soluble drugs.

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy.

PubMed

Shin, Jong Wook; Jeong, Hye Seon; Kwon, Hyon-Jo; Song, Kyu Sang; Kim, Jei

2018-01-01

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2-3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy

PubMed Central

Shin, Jong Wook; Jeong, Hye Seon; Kwon, Hyon-Jo; Song, Kyu Sang

2018-01-01

We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2–3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images. PMID:29782513

Superoxide scavenging effects of N-acetylcysteine and vitamin C in subjects with essential hypertension.

PubMed

Schneider, Markus P; Delles, Christian; Schmidt, Bernhard M W; Oehmer, Sebastian; Schwarz, Thomas K; Schmieder, Roland E; John, Stefan

2005-08-01

It is not known whether the beneficial effects of N-acetylcysteine (NAC) in conditions associated with increased oxidative stress are caused by direct superoxide scavenging. We therefore compared the acute superoxide scavenging efficacy of NAC against vitamin C (VITC) on impaired endothelium-dependent vasodilation in subjects with essential hypertension. In a cross-over randomized study, the effects of intra-arterial administration of either NAC (48 mg/min) or VITC (18 mg/min) were examined in 15 subjects with essential hypertension and in 15 normotensive control subjects. Both endothelium-dependent and endothelium-independent vasodilation were determined as forearm blood flow (FBF) response to the intra-arterial administration of acetylcholine (Ach) and sodium nitroprusside (NP) in doses of 12 and 48 mug/min and 3.2 and 12.8 mug/min, respectively. Subjects with essential hypertension had impaired responses to both doses of Ach (Delta% FBF to higher dose of Ach: 325 +/- 146 in subjects with essential hypertension v 540 +/- 199 in control subjects; P = .02) and an impaired response to the higher dose of NP (330 +/- 108 v 500 +/- 199; P = .03). The intra-arterial administration of NAC had no effect on these responses (higher dose of Ach: 325 +/- 146 without v 338 +/- 112 with NAC, NS). In contrast, intra-arterial VITC improved both the response to Ach (320 +/- 132 without v 400 +/- 185 with VITC, P = .05) and to NP (383 +/- 162 v 447 +/- 170, P = .05). We found that NAC showed no statistically significant effect on either endothelium-dependent or endothelium-independent vasodilation in hypertensive subjects, whereas VITC did. We conclude that NAC is therefore not an effective superoxide scavenger in vivo. Other, nonimmediate effects such as the generation of glutathione may explain the beneficial effects of NAC in conditions associated with oxidative stress.

Mesenchymal stem cells ameliorate podocyte injury and proteinuria in a type 1 diabetic nephropathy rat model.

PubMed

Wang, Shuai; Li, Yi; Zhao, Jinghong; Zhang, Jingbo; Huang, Yunjian

2013-04-01

Mesenchymal stem cells (MSC) attenuate albuminuria and preserve normal renal histology in diabetic mice. However, the effects of MSC on glomerular podocyte injury remain uncertain. The aim of this study was to evaluate the effects of MSC on podocyte injury in streptozotocin (STZ)-induced diabetic rats. Thirty days after diabetes induction by STZ injection (65 mg/kg, intraperitoneally) in Sprague-Dawley rats, the diabetic rats received medium or 2 × 10(6) enhanced green fluorescent protein-labeled MSC via the renal artery. In vivo tracking of MSC was followed by immunofluorescence analysis. Diabetes-related physical and biochemical parameters were measured on day 60 after the MSC infusion. The expression of podocyte markers (nephrin and podocin), podocyte survival factors (VEGF and BMP-7), and the ultrastructural pathology of podocytes were also assessed. MSC were only detected in the glomeruli from the left kidney receiving MSC infusion. Compared with medium-treated diabetic rats, rats treated with MSC showed a suppressed increase in kidney weight, kidney to body weight index, creatinine clearance rate, and urinary albumin to creatinine ratio; however, the treatment had no effect on blood glucose or body weight levels. Furthermore, the MSC treatment reduced the loss of podocytes, effacement of foot processes, widening of foot processes, thickening of glomerular basal membrane (GBM), and loss of glomerular nephrin and podocin. Most important, MSC-injected kidneys expressed higher levels of BMP-7 but not of VEGF. Our results clearly demonstrated that intra-arterial administration of MSC prevented the development of albuminuria as well as any damage to or loss of podocytes, though there was no improvement in blood sugar levels. The protective effects of MSC may be mediated in part by increasing BMP-7 secretion. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.

PubMed

Schinzari, Francesca; Tesauro, Manfredi; Veneziani, Augusto; Mores, Nadia; Di Daniele, Nicola; Cardillo, Carmine

2018-01-01

Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1-7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1-7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1-7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P <0.001); nitric oxide inhibition by l- N -monomethylarginine (4 µmol/min) during concurrent endothelin A antagonism resulted in similar vasoconstriction in the absence or presence of Ang-(1-7 Ang-(1-7) ( P =0.69). Our findings indicate that in obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity. © 2017 American Heart Association, Inc.

C-peptide has no effect on forearm blood flow during local hyperinsulinaemia in healthy humans

PubMed Central

Langenberger, Herbert; Schaller, Georg; Pleiner, Johannes; Mittermayer, Friedrich; Bayerle-Eder, Michaela; Wolzt, Michael

2003-01-01

Background C-peptide increases forearm blood flow (FBF) in patients with Type 1 diabetes, probably by interaction with insulin, but not in healthy subjects. It is unclear if the vasodilating effect is sealed at normal fasting insulin concentrations. Methods The effects of C-peptide alone and during local hyperinsulinaemia were studied in healthy young men. Subjects received intra-arterial insulin at 6 pmol min−1 (low dose) or placebo for 60 min with subsequent coinfusion of C-peptide at increasing doses of 2–60 pmol min−1 in a double-blind crossover study (n = 8). In control experiments insulin at 30 pmol min−1 (high dose) was coinfused with C-peptide (n = 3). FBF was measured by strain-gauge plethysmography. Results Placebo had no effect on FBF (mean percentage change from baseline at 50 min −3.1%, 95% confidence interval [CI]−14.9, + 8.7). Insulin infusion slightly enhanced FBF by + 10.2% (95% CI −6.8, + 27.2; low dose) and + 17.6% (95% CI −38.8, + 74.0; high dose), respectively. The mean individual difference of the change in FBF between low-dose insulin and placebo was + 13.3% (95% CI −6.0, + 32.7; P = NS). Infusion of C-peptide increased local C-peptide concentrations from 1.8 ± 0.1 ng ml−1 to 6.1 ± 2.8 ng ml−1, but had no effect on FBF during placebo or hyperinsulinaemia (mean difference vs low dose insulin −16.0%, 95% CI −38.9, + 6.9). Conclusion The vasodilating effect of C-peptide seen in Type 1 diabetes is not detectable during fasting or hyperinsulinaemia in the forearm vasculature of healthy subjects. This suggests saturation of its vasodilating potency at insulin concentrations within the normal or in the supraphysiological range. PMID:12814445

Infrared Imaging of Nitric Oxide-Mediated Blood Flow in Human Sickle Cell Disease

PubMed Central

Gorbach, Alexander M.; Ackerman, Hans C.; Liu, Wei-Min; Meyer, Joseph M.; Littel, Patricia L.; Seamon, Catherine; Footman, Eleni; Chi, Amy; Zorca, Suzana; Krajewski, Megan L.; Cuttica, Michael J.; Machado, Roberto F.; Cannon, Richard O.; Kato, Gregory J.

2012-01-01

Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous blood flow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1° C, p < 0.0001) and SNP (+0.9° C, p < 0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100mL, p < 0.0001; rs = 0.57, p = 0.003; SNP: +8.6 mL/min/100mL, p < 0.0001; r = 0.70, p = 0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8±0.2° C, 6.0±0.4 mL/min/100mL; r = 0.58, p = 0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r = −0.61, p = 0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R2 = 0.84, p < 0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD. PMID:22784510

Anatomy of liver arteries for interventional radiology.

PubMed

Favelier, S; Germain, T; Genson, P-Y; Cercueil, J-P; Denys, A; Krausé, D; Guiu, B

2015-06-01

The availability of intra-arterial hepatic therapies (radio and/or chemo-embolisation, intra-arterial hepatic chemotherapy) has convinced radiologists to perfect their knowledge of the anatomy of the liver arteries. These sometimes, complex procedures most often require selective arterial catheterization. Knowledge of the different arteries in the liver and the peripheral organs is therefore essential to optimize the procedure and avoid eventual complications. This paper aims to describe the anatomy of the liver arteries and the variants, applying it to angiography images, and to understand the implications of such variations in interventional radiological procedures. Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Two cases of Bezold-Jarisch reflex induced by intra-arterial nitroglycerin in critical left main coronary artery stenosis.

PubMed

Shah, Sachin P; Waxman, Sergio

2013-01-01

The Bezold-Jarisch reflex, a well-described phenomenon, occurs upon the stimulation of intracardiac mechanoreceptors and is mediated by vagal afferent nerve fibers. Several factors can sensitize the cardiovascular system to develop this reflex, including acute myocardial ischemia, natriuretic peptides, and, rarely, nitroglycerin administration in the setting of acute myocardial infarction. The development of the Bezold-Jarisch reflex in the presence of severe coronary artery stenosis, specifically left main coronary artery stenosis, has not been described. We report 2 cases of patients who underwent elective coronary angiography and were given intra-arterial nitroglycerin during radial sheath insertion to reduce radial artery spasm. In both patients, bradycardia and hypotension developed along with diaphoresis, consistent with the Bezold-Jarisch reflex. Coronary angiography revealed critical (>90%) left main coronary artery stenosis in both patients. Critical left main coronary artery stenosis might sensitize mechanoreceptors or vagal afferents to the development of the Bezold-Jarisch reflex after intra-arterial nitroglycerin use; however, the mechanism of this possible relationship is unclear. In addition to discussing our patients' cases, we review the medical literature relevant to the Bezold-Jarisch reflex.

Intravascular flow detection during transforaminal epidural injections: a prospective assessment.

PubMed

El Abd, Omar Hamman; Amadera, Joao Eduardo Daud; Pimentel, Daniel Camargo; Pimentel, Thais Spacov Camargo

2014-01-01

Transforaminal epidural steroid injections (TFESI) are a mainstay in the treatment of spine pain. Though this commonly performed procedure is generally felt to be safe, devastating complications following inadvertent intra-arterial injections of particulate steroid have been reported. The use of digital subtraction angiography (DSA) has been suggested as a means of detecting intra-arterial needle placements prior to medication injection. To examine the efficacy of DSA in detecting intra-arterial needle placements during TFESI. Prospective cohort study evaluating the impact of DSA on detecting intra-arterial needle placements during TFESI. We enrolled 150 consecutive patients presenting to a university-affiliated spine center with discogenic and/or radicular symptoms affecting the cervical, lumbar, and sacral regions. For each injection, prior to imaging with DSA, traditional methods for vascular penetration detection were employed, including the identification of blood in the needle hub (flash), negative aspiration of blood prior to injection, and live fluoroscopic injection of contrast. Once these tests were performed and negative for signs of intra-arterial needle placement, DSA imaging was utilized prior to medication administration for identification of vascular flow. A total number of 222 TFESI were performed, 41 injections at the cervical levels (18.47%), 113 at the lumbar levels (50.9%), and 68 at the sacral levels (30.36%). Flash was observed in 13 injections performed (5.85% of the total number of injections): one (0.45%) in the cervical, 2 (0.9%) in the lumbar, and 10 (4.5%) in the sacral levels. In 11 TFESI blood aspiration was obtained (4.95% of all injections): 3 (1.3%) in cervical, 4 (1.8%) in lumbar, and 4 (1.8%) in sacral injections. Live fluoroscopy during contrast injection detected 46 (20.72%) intravascular flow patterns: 7 (3.1%) cervical, 17 (7.6%) lumbar, and 22 (9.9%) sacral. DSA identified an additional 5 intravascular injections after all previous steps had resulted in negative vascular penetration signs, which accounted for 2.25% of all injections. This is a prospective, single-center study with a relatively small number of patients and no control group. DSA detected additional 5.26% intravascular needle placements following traditional methods. Our findings also support other studies that conclude TFESI are generally a safe procedure. We recommend that special attention should be paid to the sacral injections as vascular penetration was statistically higher than at other levels.

Vascular dementia: Pharmacological treatment approaches and perspectives

PubMed Central

Baskys, Andrius; Hou, Anthony C

2007-01-01

Vascular dementia is a common condition for which there are no effective approved pharmacological treatments available. Absence of effective treatments creates a difficult situation for those suffering from the disease, their caregivers, and healthcare providers. This review will address our current understanding of the mechanisms of nerve cell damage due to ischemia and summarize available clinical trial data on several commonly used compounds including memantine, donepezil, galantamine, rivastigmine, nimodipine, hydergine, nicergoline, CDP-choline, folic acid, as well as such nonpharmacological approaches as validation therapy. PMID:18044183

Renal artery embolization in a child with delayed hemodynamic instability from penetrating knife wound.

PubMed

Barras, M; Pearson, E; Cousin, I; Le Rouzic, C; Thepaut, M; Gentric, J-C; Roue, J-M; Yevich, S; de Vries, P

2018-06-14

Penetrating laceration injury in the pediatric population may present as an acute or delayed life-threatening injury. Although emergent intra-arterial embolization is commonly utilized in adults, few cases have been reported for children. Surgical treatment for severe renal laceration injuries may require complete nephrectomy; an unfortunate outcome for a pediatric patient if a renal-preserving alternative is feasible. We present a case of penetrating renal laceration in a 10-year-old boy treated with intra-arterial embolization of the lacerated dominant renal artery and subsequent renal perfusion by an uninjured accessory renal artery allowing for renal preservation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Intra-arterial pressure measurement in neonates: dynamic response requirements.

PubMed

van Genderingen, H R; Gevers, M; Hack, W W

1995-02-01

A computer simulation of a catheter manometer system was used to quantify measurement errors in neonatal blood pressure parameters. Accurate intra-arterial pressure recordings of 21 critically ill newborns were fed into this simulated system. The dynamic characteristics, natural frequency and damping coefficient, were varied from 2.5 to 60 Hz and from 0.1 to 1.4, respectively. As a result, errors in systolic, diastolic and pulse arterial pressure were obtained as a function of natural frequency and damping coefficient. Iso-error curves for 2%, 5% and 10% were constructed. Using these curves, the maximum inaccuracy of any neonatal catheter manometer system can be determined and used in the clinical setting.

The effects of catecholamines and adrenoceptor blocking drugs on the canine peripheral lymph flow.

PubMed Central

De Micheli, P; Glässer, A H

1975-01-01

Blood flow through the femoral artery, lymph flow in a lymphatic vessel in the femoral triangle and metatarsal distal venous pressure were measured simultaneously in a canine moving hind limb. 2. Low intra-arterial doses of adrenaline and noradrenaline increased lymph flow even in the presence of marked arterial vasoconstriction. In contrast, isoprenaline increased arterial blood flow without affecting lymph flow rate. 3. Phenoxybenzamine, dihydroergotoxine, and nicergoline did not inhibit the lymphatic flow increase induced by adrenaline at doses active on arterial or venous vascular alpha-adrenoceptors. 4. Propranolol given intra-arterially into animals pretreated with alpha-adrenoceptor blocking agents restored the vasoconstrictor effect of adrenaline (reversal of adrenaline reversal). PMID:238702

Methodological assessment of the reduction of the content of impurities in nimodipine emulsion via the use of 21 amino acid protection

PubMed Central

Xie, Yiqiao; Zhuang, Zhiquan; Zhang, Shu; Xia, Zihua; Chen, De; Fan, Kaiyan; Ren, Jialin; Lin, CuiCui; Chen, Yanzhong; Yang, Fan

2017-01-01

Purpose The present study examined the factors affecting the content of impurities of nimodipine (NMP) emulsion and the associated methods of compound protection. Methods Destructive testing of NMP emulsion and its active pharmaceutical ingredient (API) were conducted, and ultracentrifugation was used to study the content of impurities in two phases. The impurity of NMP was measured under different potential of hydrogen (pH) conditions, antioxidants and pH-adjusting agents. Results Following destruction, the degradation of NMP notably occurred in the basic environment. The consumption of the pH-adjusting agent NaOH was proportional to the production of impurities since the inorganic base and/or acid promoted the degradation of NMP. The organic antioxidants, notably amino acids with an appropriate length of intermediate chain and electron-donating side group, exhibited improved antioxidant effects compared with inorganic antioxidants. The minimal amount of impurities was produced following addition of 0.04% lysine and 0.06% leucine in the aqueous phase and adjustment of the pH to a range of 7.5–8.0 in the presence of acetic acid solution. Conclusion NMP was more prone to degradation in an oxidative environment, in an aqueous phase and/or in the presence of inorganic pH-adjusting agents and antioxidants. The appropriate antioxidant and pH-adjusting agent should be selected according to the chemical structure, while destructive testing of the drug is considered to play the optimal protective effect. PMID:28490879

Effect of pore size of three-dimensionally ordered macroporous chitosan-silica matrix on solubility, drug release, and oral bioavailability of loaded-nimodipine.

PubMed

Gao, Yikun; Xie, Yuling; Sun, Hongrui; Zhao, Qinfu; Zheng, Xin; Wang, Siling; Jiang, Tongying

2016-01-01

To explore the effect of the pore size of three-dimensionally ordered macroporous chitosan-silica (3D-CS) matrix on the solubility, drug release, and oral bioavailability of the loaded drug. 3D-CS matrices with pore sizes of 180 nm, 470 nm, and 930 nm were prepared. Nimodipine (NMDP) was used as the drug model. The morphology, specific surface area, and chitosan mass ratio of the 3D-CS matrices were characterized before the effect of the pore size on drug crystallinity, solubility, release, and in vivo pharmacokinetics were investigated. With the pore size of 3D-CS matrix decreasing, the drug crystallinity decreased and the aqueous solubility increased. The drug release was synthetically controlled by the pore size and chitosan content of 3D-CS matrix in a pH 6.8 medium, while in a pH 1.2 medium the erosion of the 3D-CS matrix played an important role in the decreased drug release rate. The area under the curve of the drug-loaded 3D-CS matrices with pore sizes of 930 nm, 470 nm, and 180 nm was 7.46-fold, 5.85-fold, and 3.75-fold larger than that of raw NMDP respectively. Our findings suggest that the oral bioavailability decreased with a decrease in the pore size of the matrix.

Aldosterone downregulates delayed rectifier potassium currents through an angiotensin type 1 receptor-dependent mechanism.

PubMed

Lv, Yankun; Wang, Yanjun; Zhu, Xiaoran; Zhang, Hua

2018-01-01

We have previously shown that aldosterone downregulates delayed rectifier potassium currents (I Ks ) via activation of the mineralocorticoid receptor (MR) in adult guinea pig cardiomyocytes. Here, we investigate whether angiotensin II/angiotensin type 1 receptor (AngII/AT1R) and intracellular calcium also play a role in these effects. Ventricular cardiomyocytes were isolated from adult guinea pigs and incubated with aldosterone (1 μmol·L -1 ) either alone or in combination with enalapril (1 μmol·L -1 ), losartan (1 μmol·L -1 ), nimodipine (1 μmol·L -1 ), or BAPTA-AM (2.5 μmol·L -1 ) for 24 h. We used the conventional whole cell patch-clamp technique to record the I Ks component. In addition, we evaluated expression of the I Ks subunits KCNQ1 and KCNE1 using Western blotting. Our results showed that both enalapril and losartan, but not nimodipine or BAPTA-AM, completely reversed the aldosterone-induced inhibition of I Ks and its effects on KCNQ1/KCNE1 protein levels. Furthermore, we found that AngII/AT1R mediates the inhibitory effects of aldosterone on I Ks . Finally, the downregulation of I Ks induced by aldosterone did not occur secondarily to a change in intracellular calcium concentrations. Taken together, our findings demonstrate that crosstalk between MR and AT1R underlies the effects of aldosterone, and provide new insights into the mechanism underlying potassium channels.

Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

NASA Astrophysics Data System (ADS)

Mikado, S.; Yanagie, H.; Yasuda, N.; Higashi, S.; Ikushima, I.; Mizumachi, R.; Murata, Y.; Morishita, Y.; Nishimura, R.; Shinohara, A.; Ogura, K.; Sugiyama, H.; Iikura, H.; Ando, H.; Ishimoto, M.; Takamoto, S.; Eriguchi, M.; Takahashi, H.; Kimura, M.

2009-06-01

It is necessary to accumulate the 10B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy (BNCT). In order to achieve an accurate measurement of 10B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of 10BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The 10B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of 10B atoms in the VX-2 tumor by intra-arterial injection of 10B entrapped WOW emulsion until 3 days after injection by using digitized NCAR images (i.e. alpha-track mapping).

Liver transplantation and chemotherapy for hepatoblastoma and hepatocellular cancer in childhood and adolescence.

PubMed

Reyes, J D; Carr, B; Dvorchik, I; Kocoshis, S; Jaffe, R; Gerber, D; Mazariegos, G V; Bueno, J; Selby, R

2000-06-01

To describe our experience with total hepatectomy and liver transplantation as treatment for primary hepatoblastoma (HBL) and hepatocellular carcinoma (HCC) in children. A retrospective analysis of the perioperative course of 31 children with unresectable primary HBL (n = 12) and HCC (n = 19) who underwent transplantation between May 1989 and December 1998. Systemic (n = 18) and intraarterial (n = 7) neoadjuvant chemotherapy were administered; follow-up ranged from 1 to 185 months. For HBL, 1-year, 3-year, and 5-year posttransplantation survival rates were 92%, 92%, and 83%, respectively. Intravenous invasion, positive hilar lymph nodes, and contiguous spread did not have a significant adverse effect on outcome; distant metastasis was responsible for 2 deaths. Intraarterial chemotherapy was effective in all patients treated. For HCC, the overall 1-year, 3-year, and 5-year disease-free survival rates were 79%, 68%, and 63%, respectively. Vascular invasion, distant metastases, lymph node involvement, tumor size, and gender were significant risk factors for recurrence. Intraarterial chemotherapy was effective in 1 of 3 patients. Six patients died of recurrent HCC, and 3 deaths were unrelated to recurrent tumor. Liver transplantation for unresectable HBL and HCC can be curative. Risk factors for recurrence were significant only for HCC, with more advanced stages amenable to cure in the HBL group.

Success of intra-arterial chemotherapy (chemosurgery) for retinoblastoma: effect of orbitovascular anatomy.

PubMed

Marr, Brian P; Hung, Crystal; Gobin, Yves P; Dunkel, Ira J; Brodie, Scott E; Abramson, David H

2012-02-01

To review results of orbital angiography performed during intra-arterial chemotherapy (chemosurgery) for treatment of retinoblastoma to assess the association of angiographic variability in orbitovascular anatomy with tumor response and outcomes. Medical records and 64 orbital angiograms were reviewed for 56 pediatric patients with retinoblastoma undergoing chemosurgery using a combination of melphalan hydrochloride, topotecan hydrochloride, or carboplatin. The major orbital arteries and capillary blush patterns were graded, and tumor response and recurrence were compared using the log-rank and Fisher exact tests. Statistically significant variables for tumor response were lacrimal artery prominence (P = .001), previous treatment (P = .003), and lacrimal blush (P = .004). The only statistically significant variable for vitreous seed response was ciliary body blush (P = .03). Statistically significant variables influencing time to recurrence and time to enucleation were choroidal blush absence (P = .01) and lacrimal artery presence (P = .03), respectively. The success of intra-arterial chemotherapy is dependent on delivery of drug to the target tumor within the eye via the ophthalmic artery. Because of the small volume of drug used (0.50-1.25 mL per treatment) and the selectivity of catheterization, variables affecting orbital blood flow greatly influence drug delivery and the success of chemosurgery.

Intra-arterial Ultra-low-Dose CT Angiography of Lower Extremity in Diabetic Patients

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

Özgen, Ali, E-mail: draliozgen@hotmail.com; Sanioğlu, Soner; Bingöl, Uğur Anıl

2016-08-15

PurposeTo image lower extremity arteries by CT angiography using a very low-dose intra-arterial contrast medium in patients with high risk of developing contrast-induced nephropathy (CIN).Materials and MethodsThree cases with long-standing diabetes mellitus and signs of lower extremity atherosclerotic disease were evaluated by CT angiography using 0.1 ml/kg of the body weight of contrast medium given via 10-cm-long 4F introducer by puncturing the CFA. Images were evaluated by an interventional radiologist and a cardiovascular surgeon. Density values of the lower extremity arteries were also calculated. Findings in two cases were compared with digital subtraction angiography images performed for percutaneous revascularization. Blood creatininemore » levels were followed for possible CIN.ResultsIntra-arterial CT angiography images were considered diagnostic in all patients and optimal in one patient. No patient developed CIN after intra-arterial CT angiography, while one patient developed CIN after percutaneous intervention.ConclusionIntra-arterial CT angiography of lower extremity might be performed in selected patients with high risk of developing CIN. Our limited experience suggests that as low as of 0.1 ml/kg of the body weight of contrast medium may result in adequate diagnostic imaging.« less

The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

PubMed

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

PubMed Central

Jae, Hwan Jun; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

Objective The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. Materials and Methods This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. Results The tumor necrosis rate was significantly higher in the high dose group (93% ± 7.6 [mean ± SD]) than that in the control group (48% ± 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% ± 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% ± 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Conclusion Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method. PMID:19885316

Intra-Arterial Therapy for Acute Stroke and the Effect of Technological Advances on Recanalization: Findings in a Community Hospital.

PubMed

Goldstein, Jonas H; Denslow, Sheri A; Goldstein, Samuel J; Marx, William F; Short, John G; Taylor, Reid D; Schneider, Alexander L

2016-01-01

Recent randomized controlled studies have shown improvement in recanalization outcomes when physicians use the latest intra-arterial therapy devices in patients with acute, large-vessel, intracranial occlusions. The goal of this study was to explore how new procedures affected degree of and time to recanalization at a single center over the past 12 years as technology has improved. Patients were included in the study if they had a large or medium intracranial vessel occlusion and had undergone intra-arterial therapy for acute stroke during the period 2002-2013. Therapies were categorized as intra-arterial thrombolysis with tissue plasminogen activator (IA tPA), mechanical thrombectomy using 1st-generation devices (Merci and Penumbra), or mechanical thrombectomy using 2nd-generation devices (stent-trievers). Recanalization was defined using a modified Thrombolysis in Cerebral Infarction (TICI) scale. Primary treatment was IA tPA in 24 (12.4%) patients, 1st-generation devices in 128 (66.0%) patients, and 2nd-generation devices in 42 (21.6%) patients. TICI 2b was achieved in 7 (29.2%) patients treated with IA tPA, in 79 (61.7%) patients treated with 1st-generation devices, and in 38 (90.5%) patients treated with 2nd-generation devices. Compared to patients treated with IA tPA, patients treated with 2nd-generation devices were more likely to reach TICI 2b recanalization (odds ratio, 11.66; 95% CI, 1.56-87.01), and they did so in shorter times. Technological advances over 12 years in endovascular stroke treatments significantly improved the chance of and reduced time to achieving TICI 2b recanalization in our community hospital. This shows the importance of adopting new technologies in a rapidly evolving field in order to provide the best-practice standard of care for the people of our region. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

Intraarterial Microdosing, a Novel Drug Development Approach, Proof-of-Concept PET Study in Rats

PubMed Central

Burt, Tal; Rouse, Douglas C.; Lee, Kihak; Wu, Huali; Layton, Anita T.; Hawk, Thomas C.; Weitzel, Douglas H.; Chin, Bennett B.; Cohen-Wolkowiez, Michael; Chow, Shein-Chung; Noveck, Robert J.

2016-01-01

Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. Methods Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min 18F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The 18F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. Results 18F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], −0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, −0.045 to −0.007; P = 0.0147) and sham intervention (−0.0015; 95% CI, 0.023–0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose–insulin dynamics. Conclusion Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs. PMID:26315828

Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol.

PubMed

Neuman, Robert B; Hayek, Salim S; Poole, Joseph C; Rahman, Ayaz; Menon, Vivek; Kavtaradze, Nino; Polhemus, David; Veledar, Emir; Lefer, David J; Quyyumi, Arshed A

2016-03-01

Endothelial dysfunction is more prevalent in African Americans (AAs) compared with whites. The authors hypothesized that nebivolol, a selective β1 -antagonist that stimulates nitric oxide (NO), will improve endothelial function in AAs with hypertension when compared with metoprolol. In a double-blind, randomized, crossover study, 19 AA hypertensive patients were randomized to a 12-week treatment period with either nebivolol 10 mg or metoprolol succinate 100 mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-N(G) -monomethylarginine (L-NMMA) and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared with metoprolol treatment (21% vs 12% reduction in FBF, P=.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (P<.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared with metoprolol in AAs with hypertension. © 2015 Wiley Periodicals, Inc.

Nitric Oxide Contributes to Vasomotor Tone in Hypertensive African Americans Treated With Nebivolol and Metoprolol

PubMed Central

Neuman, Robert B.; Hayek, Salim; Poole, Joseph C.; Rahman, Ayaz; Menon, Vivek; Kavtaradze, Nino; Polhemus, David; Veledar, Emir; Lefer, David J.; Quyyumi, Arshed A.

2015-01-01

Endothelial dysfunction is more prevalent in African Americans (AA) compared to whites. We hypothesized that nebivolol, a selective β-1 antagonist that stimulates NO, will improve endothelial function in AA with hypertension when compared to metoprolol. In a double-blind, randomized, cross-over study, 19 AA hypertensive subjects were randomized to a 12-week treatment period with either nebivolol 10mg or metoprolol succinate 100mg daily. Forearm blood flow (FBF) was measured using plethysmography at rest and after intra-arterial infusion of acetylcholine, and sodium nitroprusside to estimate endothelium-dependent and independent vasodilation, respectively. Physiologic vasodilation was assessed during hand-grip exercise. Measurements were repeated after NO blockade with L-NG-monomethylarginine (L-NMMA), and after inhibition of endothelium-derived hyperpolarizing factor (EDHF) with tetraethylammonium chloride (TEA). NO blockade with L-NMMA produced a trend toward greater vasoconstriction during nebivolol compared to metoprolol treatment period (21% vs 12% reduction in FBF, p=0.06, respectively). This difference was more significant after combined administration of L-NMMA and TEA (p<0.001). Similarly, there was a contribution of NO to exercise-induced vasodilation during nebivolol but not during metoprolol treatment. There were significantly greater contributions of NO and EDHF to resting vasodilator tone and of NO to exercise-induced vasodilation with nebivolol compared to metoprolol in AA with hypertension. PMID:26285691

Delivery of Chemotherapeutics Across the Blood–Brain Barrier: Challenges and Advances

PubMed Central

Doolittle, Nancy D.; Muldoon, Leslie L.; Culp, Aliana Y.; Neuwelt, Edward A.

2017-01-01

The blood–brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2–26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. PMID:25307218

Patient Selection and Activity Planning Guide for Selective Internal Radiotherapy With Yttrium-90 Resin Microspheres

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

Lau, Wan-Yee, E-mail: josephlau@surgery.cuhk.edu.hk; Kennedy, Andrew S.; Department of Biomedical Engineering, North Carolina State University, Raleigh, NC

Purpose: Selective internal radiotherapy (SIRT) with yttrium-90 ({sup 90}Y) resin microspheres can improve the clinical outcomes for selected patients with inoperable liver cancer. This technique involves intra-arterial delivery of {beta}-emitting microspheres into hepatocellular carcinomas or liver metastases while sparing uninvolved structures. Its unique mode of action, including both {sup 90}Y brachytherapy and embolization of neoplastic microvasculature, necessitates activity planning methods specific to SIRT. Methods and Materials: A panel of clinicians experienced in {sup 90}Y resin microsphere SIRT was convened to integrate clinical experience with the published data to propose an activity planning pathway for radioembolization. Results: Accurate planning is essentialmore » to minimize potentially fatal sequelae such as radiation-induced liver disease while delivering tumoricidal {sup 90}Y activity. Planning methods have included empiric dosing according to degree of tumor involvement, empiric dosing adjusted for the body surface area, and partition model calculations using Medical Internal Radiation Dose principles. It has been recommended that at least two of these methods be compared when calculating the microsphere activity for each patient. Conclusions: Many factors inform {sup 90}Y resin microsphere SIRT activity planning, including the therapeutic intent, tissue and vasculature imaging, tumor and uninvolved liver characteristics, previous therapies, and localization of the microsphere infusion. The influence of each of these factors has been discussed.« less

Role of endopeptidase 3.4.24.16 in the catabolism of neurotensin, in vivo, in the vascularly perfused dog ileum.

PubMed Central

Barelli, H.; Fox-Threlkeld, J. E.; Dive, V.; Daniel, E. E.; Vincent, J. P.; Checler, F.

1994-01-01

1. The degradation of tritiated and unlabelled neurotensin (NT) following close intra-arterial infusion of the peptides in ileal segments of anaesthetized dogs was examined. 2. Intact NT and its catabolites recovered in the venous effluents were purified by chromatography on Sep-Pak columns followed by reverse-phase h.p.l.c. and identified by their retention times or by radioimmunoassay. 3. The half-life of neurotensin was estimated to be between 2 and 6 min. Four labelled catabolites, corresponding to free tyrosine, neurotensin (1-8), neurotensin (1-10) and neurotensin (1-11), were detected. 4. Neurotensin (1-11) was mainly generated by a phosphoramidon-sensitive cleavage, probably elicited by endopeptidase 24-11. 5. Two endopeptidase 3.4.24.16 inhibitors, phosphodiepryl 03 and the dipeptide Pro-Ile, dose-dependently potentiated the recovery of intact neurotensin. Furthermore, both agents inhibited the formation of neurotensin (1-10), the product that results from the hydrolysis of neurotensin by purified endopeptidase 3.4.24.16. In contrast, the endopeptidase 3.4.24.15 inhibitor Cpp-AAY-pAB neither protected neurotensin from degradation nor modified the production of neurotensin (1-10). 6. Our study is the first evidence to indicate that endopeptidase 3.4.24.16 contributes to the catabolism of neurotensin, in vivo, in the dog intestine. PMID:8032633

A case of unresectable combined hepatocellular cholangiocarcinoma showing favorable response to LFP therapy.

PubMed

Kato, Sayuri; Takeuchi, Yasuto; Wada, Nozomu; Morimoto, Yuuki; Kuwaki, Kenji; Ohnishi, Hideki; Nakamura, Shinichiro; Shiraha, Hidenori; Takaki, Akinobu; Okada, Hiroyuki

2016-01-01

A woman in her 50s was admitted to our hospital because of multiple tumors detected in her liver. She was diagnosed with combined hepatocellular cholangiocarcinoma using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biopsy of the liver tumors. We judged the tumors to be unresectable because they were found in both lobes of the liver, with a tumor thrombus being found in the main left portal vein. The pathological findings showed that the tumors exhibited characteristics of hepatocellular carcinoma. Therefore, sorafenib was administered;however, 6 months later, the disease progressed. Consequently, she received second-line chemotherapy with a one-shot intra-arterial injection of cisplatin, but this too was ineffective, and her general condition worsened. As hence, we changed the regimen to 5-fluorouracil continuous infusion and consecutive low dose cisplatin (LFP) therapy. After one cycle of chemotherapy with LFP, Gd-EOB-DTPA-enhanced MRI showed markedly decreased sizes and numbers of tumors. To date, she has completed six cycles of LFP therapy, and almost all her tumors are no longer visible on MRI. She has recovered to a good state and has achieved long-term survival. Thus, this case indicates that although LFP therapy is generally selected for cases of advanced hepatocellular carcinoma, it also appears to be effective for long-term disease control in cases of hepatocellular cholangiocarcinoma.

Cerebral angiography

MedlinePlus

... Carotid angiogram; Cervicocerebral catheter-based angiography; Intra-arterial digital subtraction angiography; IADSA ... with the dye are seen. This is called digital subtraction angiography (DSA). After the x-rays are ...

The Cardiovascular Effects of Morphine THE PERIPHERAL CAPACITANCE AND RESISTANCE VESSELS IN HUMAN SUBJECTS

PubMed Central

Zelis, Robert; Mansour, Edward J.; Capone, Robert J.; Mason, Dean T.

1974-01-01

To evaluate the effects of morphine on the peripheral venous and arterial beds, 69 normal subjects were evaluated before and after the intravenous administration of 15 mg morphine. Venous tone was determined by three independent techniques in 22 subjects. The venous pressure measured in a hand vein during temporary circulatory arrest (isolated hand vein technique) fell from 20.2±1.4 to 13.4±0.9 mm Hg (P < 0.01) 10 min after morphine, indicating that a significant venodilation had occurred. With the acute occlusion technique, morphine induced a reduction in forearm venous tone from 12.8±1.1 to 7.9±2.3 mm Hg/ml/100 ml (P < 0.01). Although forearm venous volume at a pressure of 30 mm Hg (VV[30]) was increased from 2.26±0.17 to 2.55±0.26 ml/100 ml, measured by the equilibration technique, the change was not significant (P > 0.1). Of note is that the initial reaction to morphine was a pronounced venoconstriction, demonstrated during the first 1-2 min after the drug. (Isolated hand vein pressure increased to 37.2±5.4 mm Hg, P < 0.01). This rapidly subsided, and by 5 min a venodilation was evident. Morphine did not attenuate the venoconstrictor response to a single deep breath, mental arithmetic, or the application of ice to the forehead when measured by either the isolated hand vein technique or the equilibration technique. To evaluate the effects of morphine on the peripheral resistance vessels in 47 normal subjects, forearm blood flow was measured plethysmographically before and 10-15 min after the intravenous administration of 15 mg of morphine. Although mean systemic arterial pressure was unchanged, forearm blood flow increased from 2.92±0.28 to 3.96±0.46 ml/min/100 ml (P < 0.01), and calculated vascular resistance fell from 42.4±5.2 to 31.6±3.2 mm Hg/ml/min/100 ml (P < 0.01). When subjects were tilted to the 45° head-up position, morphine did not block the increase in total peripheral vascular resistance that occurs; however, it did significantly attenuate the forearm arteriolar constrictor response (before morphine, + 25.7±5.4; after morphine, + 13.7±5.3 mm Hg/ml/min/100 ml, P < 0.05). However, morphine did not block the post-Valsalva overshoot of blood pressure, nor did it block the increase in forearm vascular resistance produced by the application of ice to the forehead. Similarly, morphine did not block the arteriolar or venoconstrictor effects of intra-arterially administered norepinephrine. Morphine infused into the brachial artery in doses up to 200 μg/min produced no changes in ipsilateral forearm VV[30], forearm blood flow, or calculated forearm resistance. Intra-arterial promethazine, atropine, and propranolol did not block the forearm arteriolar dilator response to intravenous morphine; however, intra-arterial phentolamine abolished the response. These data suggest that in human subjects, morphine induces a peripheral venous and arteriolar dilation by a reflex reduction in sympathetic alpha adrenergic tone. Morphine does not appear to act as a peripheral alpha adrenergic blocking agent but seems to attenuate the sympathetic efferent discharge at a central nervous system level. Images PMID:4612057

Clinical Outcome after Intra-Arterial Stroke Therapy in the Very Elderly: Why is it so Heterogeneous?

PubMed Central

Chandra, Ronil V.; Leslie-Mazwi, Thabele M.; Mehta, Brijesh P.; Yoo, Albert J.; Simonsen, Claus Z.

2014-01-01

Very elderly patients (i.e., ≥80 years) are disproportionally affected by acute ischemic stroke. They account for a third of hospital stroke admissions, but two-thirds of overall stroke-related morbidity and mortality. There is some evidence of clinical benefit in treating selected very elderly patients with intravenous thrombolysis (IVT). For very elderly patients ineligible or non-responsive to IVT, intra-arterial therapy (IAT) may have promise in improving clinical outcome. However, its unequivocal efficacy in the general population remains to be proven in randomized trials. Small cohort studies reveal that the rate of good clinical outcome for very elderly patients after IAT is highly variable, ranging from 0 to 28%. In addition, they experience higher rates of futile reperfusion than younger patients. Thus, it is imperative to understand the factors that impact on clinical outcome in very elderly patients after IAT. The aim of this review is to examine the factors that may be responsible for the heterogeneous clinical response of the very elderly to IAT. This will allow the reader to integrate the current available evidence to individualize intra-arterial stroke therapy in very elderly patients. Placing emphasis on pre-stroke independent living, smaller infarct core size, short procedure times, and avoiding general anesthesia where feasible, will help improve rates of good clinical outcome. PMID:24808887

'Stroke Room': Diagnosis and Treatment at a Single Location for Rapid Intraarterial Stroke Treatment.

PubMed

Ragoschke-Schumm, Andreas; Yilmaz, Umut; Kostopoulos, Panagiotis; Lesmeister, Martin; Manitz, Matthias; Walter, Silke; Helwig, Stefan; Schwindling, Lenka; Fousse, Mathias; Haass, Anton; Garner, Dominique; Körner, Heiko; Roumia, Safwan; Grunwald, Iris; Nasreldein, Ali; Halmer, Ramona; Liu, Yang; Schlechtriemen, Thomas; Reith, Wolfgang; Fassbender, Klaus

2015-01-01

For patients with acute ischemic stroke, intra-arterial treatment (IAT) is considered to be an effective strategy for removing the obstructing clot. Because outcome crucially depends on time to treatment ('time-is-brain' concept), we assessed the effects of an intervention based on performing all the time-sensitive diagnostic and therapeutic procedures at a single location on the delay before intra-arterial stroke treatment. Consecutive acute stroke patients with large vessel occlusion who obtained IAT were evaluated before and after implementation (April 26, 2010) of an intervention focused on performing all the diagnostic and therapeutic measures at a single site ('stroke room'). After implementation of the intervention, the median intervals between admission and first angiography series were significantly shorter for 174 intervention patients (102 min, interquartile range (IQR) 85-120 min) than for 81 control patients (117 min, IQR 89-150 min; p < 0.05), as were the intervals between admission and clot removal or end of angiography (152 min, IQR 123-185 min vs. 190 min, IQR 163-227 min; p < 0.001). However, no significant differences in clinical outcome were observed. This study shows for the, to our knowledge, first time that for patients with acute ischemic stroke, stroke diagnosis and treatment at a single location ('stroke room') saves crucial time until IAT. © 2015 S. Karger AG, Basel.

Minimal invasive treatments for liver malignancies.

PubMed

Orsi, Franco; Varano, Gianluca

2015-11-01

Minimal invasive therapies have proved useful in the management of primary and secondary hepatic malignancies. The most relevant aspects of all these therapies are their minimal toxicity profiles and highly effective tumor responses without affecting the normal hepatic parenchyma. These unique characteristics coupled with their minimally invasive nature provide an attractive therapeutic option for patients who previously may have had few alternatives. Combination of these therapies might extend indications to bring curative treatment to a wider selected population. The results of various ongoing combination trials of intraarterial therapies with targeted therapies are awaited to further improve survival in this patient group. This review focuses on the application of ablative and intra-arterial therapies in the management of hepatocellular carcinoma and hepatic colorectal metastasis. Copyright © 2015 Elsevier B.V. All rights reserved.

Targeting of VX2 Rabbit Liver Tumor by Selective Delivery of 3-Bromopyruvate: A Biodistribution and Survival Study

PubMed Central

Vali, Mustafa; Vossen, Josephina A.; Buijs, Manon; Engles, James M.; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L.; Geschwind, Jean-Francois H.

2009-01-01

The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [14C]3-BrPA i.a., 1.75 mM [14C]3-BrPA i.v., 20 mM [14C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [14C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [14C]3-BrPA was 1.8 ± 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [14C]3-BrPA was 0.03 ± 0.01% ID/g. After i.a. administration of [14C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [14C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit. PMID:18591216

Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

PubMed Central

2010-01-01

Background Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions. Objectives To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures. Methods In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 μg/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions. Measurements and Main Results Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05). Conclusion Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds. PMID:20653945

Pyloric motor response to central and peripheral nitric oxide in the ferret.

PubMed

Lingenfelser, T; Blackshaw, L A; Sun, W M; Dent, J

1997-09-01

This study has investigated the relative importance of central nervous and peripheral nitroxidergic mechanisms in the control of pyloric motility. In 10 urethane-anaesthetized ferrets, drugs were administered directly to the CNS via a 0.5-mm-diameter cannula inserted into the 4th ventricle, approximately at the obex. Drugs were also given directly to the upper GI tract by close intra-arterial (i.a.) injection at the coeliac axis. Antropyloroduodenal pressures were recorded with a five-channel sleeve/sidehole micromanometric assembly (1.35 x 1.75 mm o.d.), which was introduced via the duodenum. Pyloric motility was stimulated throughout the main part of each study with a continuous i.v. infusion of CCK-8 (30 pmol min-1). This infusion produced an immediate and sustained increase in tonic and phasic pyloric activity, and sustained abolition of antral pressure waves. CCK-8 also induced a duodenal motor response, but this was short-lived (11.4 +/- 7.9 min). Coeliac axis injection of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) decreased phasic pyloric activity (from 330 +/- 35 to 148 +/- 21 mmHg min-1 after SNAP 5 micrograms, P < 0.01). By comparison central SNAP administration over the same dose range had no effect on CCK-stimulated pyloric motlity. Inhibition of endogenous NO synthase with L-Nitro Arginine Methyl Ester (L-NAME, 100 mg kg-1 close i.a.) caused a marked increase of phase pyloric motor activity from 349 +/- 59 to 1044 +/- 140 mmHg min-1 (P < 0.01). In addition, SNAP caused marked stimulation of pyloric tone from 2.6 +/- 0.5 to 13.1 +/- 2.8 mmHg (P < 0.01). Central nervous administration of L-NAME caused modest enhancement of phasic pyloric activity (248 +/- 31 to 283 +/- 32 mmHg min-1 P < 0.05) and pyloric tone (2.6 +/- 0.5 to 3.7 +/- 0.7 mmHg, P < 0.05). Our data indicate that motor activity of the ferret pylorus is potently modulated by NO released within the upper gut. Additionally, there is potential for modulation of pyloric motility by central nervous system production of NO.

FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

PubMed Central

Park, Hee Sun; Jae, Hwan Jun; Kim, Young Il; Son, Kyu Ri; Lee, Min Jong; Park, Jae Hyung; Kang, Won Jun; Yoon, Jung Hwan; Chung, Hesson; Lee, Kichang

2007-01-01

Objective We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. Materials and Methods VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. Results The SUV of the VX2 tumors before treatment (3.87 ±1.51 [mean ±SD]) was significantly higher than that of nontumorous liver parenchyma (1.72 ±0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05 ±1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41 ±0.73) than that before treatment (p = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48% ±15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. Conclusion Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor. PMID:17554189

Hepatic Intra-arterial Delivery of a "Trojan-horses" Gene Therapy: A Pilot Study on Rabbit VX2 Hepatic Tumor Model.

PubMed

Pellerin, Olivier; Amara, Ikram; Sapoval, Marc; Méachi, Tchao; Déan, Carole; Beaune, Philippe; de Waziers, Isabelle

2018-01-01

Gene-directed enzyme prodrug therapy (GDEPT) is a "Trojan-horses" suicide gene therapy that consists of tumor-targeted gene delivery (vectorized by mesenchymal stem cells MSCs) encoding an enzyme that converts a harmless prodrug into cytotoxic metabolites in situ. Then, cytotoxic metabolites passively diffuse in the neighboring tumor cells and kill them (bystander effect). The goal of our study was to assess the feasibility and efficacy of intra-arterial administration of MSCs transduced with an optimized gene (MSC-CYP2B6TM-RED) followed by intravenous administration of cyclophosphamide (CPA) into the VX2 rabbit liver tumor. Nine rabbits with a VX2 liver tumor were randomly assigned into three groups: Control group A (one rabbit) free of any treatment; Control group B (two rabbits) receiving intravenous injection of cyclophosphamide at day 3 and CPA at day 14; and Group C (six rabbits) receiving the GDEPT treatment, consisting of successive intra-arterial injection of transduced-MSCs at days 0 (n = 6) and 11 (n = 3), followed by injection of CPA at days 3 (n = 6) and 14 (n = 3). The tumor response was assessed by ultrasound scan every 7 days and histopathological analysis at sacrifice (D25). There was a significant difference in the tumor volume between control groups (A + B) and group C at D7: 38/19 cm 3 (p = 0.024); D11: 51/20 cm 3 (p = 0.024), and D25: 121/37 cm 3 (p = 0.048). Tumor necrosis was significantly greater and metastatic spread was lower for rabbits who received GDEPT (78% of total tumor surface) than for control animals (A + B) (22% of total tumor surface (p = 0.006). Intra-arterial delivery of transduced-MSCs is feasible and, after CPA injection, resulted in 78% tumor necrosis (p = 0.006) and less metastasis in a VX2 liver tumor model.

Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer's disease.

PubMed

Marco-Contelles, José; León, Rafael; de Los Ríos, Cristóbal; Guglietta, Antonio; Terencio, José; López, Manuela G; García, Antonio G; Villarroya, Mercedes

2006-12-28

In this work we describe the synthesis and biological evaluation of the tacrine-1,4-dihydropyridine (DHP) hybrids (3-11). These multipotent molecules are the result of the juxtaposition of an acetylcholinesterase inhibitor (AChEI) such as tacrine (1) and a 1,4-DHP such as nimodipine (2). Compounds 3-11 are very selective and potent AChEIs and show an excellent neuroprotective profile and a moderate Ca2+ channel blockade effect. Consequently, these molecules are new potential drugs for the treatment of Alzheimer's disease.

Quinine-induced tinnitus in rats.

PubMed

Jastreboff, P J; Brennan, J F; Sasaki, C T

1991-10-01

Quinine ingestion reportedly induces tinnitus in humans. To expand our salicylate-based animal model of tinnitus, a series of conditioned suppression experiments was performed on 54 male-pigmented rats using quinine injections to induce tinnitus. Quinine induced changes in both the extent of suppression and recovery of licking, which followed a pattern that paralleled those produced after salicylate injections, and which may be interpreted as the result of tinnitus perception in animals. These changes depended on the dose and time schedule of quinine administration. Additionally, the calcium channel blocker, nimodipine, abolished the quinine-induced effect in a dose-dependent manner.

Vildagliptin Improves Endothelium-Dependent Vasodilatation in Type 2 Diabetes

PubMed Central

van Poppel, Pleun C.M.; Netea, Mihai G.; Smits, Paul; Tack, Cees J.

2011-01-01

OBJECTIVE To investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Sixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m2, HbA1c 6.97 ± 0.61) on oral blood glucose–lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator). RESULTS Infusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL−1 ⋅ min−1 in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL−1 ⋅ min−1, respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside. CONCLUSIONS Four weeks’ treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications. PMID:21788633

Delivery of chemotherapeutics across the blood-brain barrier: challenges and advances.

PubMed

Doolittle, Nancy D; Muldoon, Leslie L; Culp, Aliana Y; Neuwelt, Edward A

2014-01-01

The blood-brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2-26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. © 2014 Elsevier Inc. All rights reserved.

Sex-specific effects of cardiovascular risk factors on endothelium-dependent dilation and endothelin activity in middle-aged women and men.

PubMed

Brar, Vijaywant; Gill, Sartaj; Cardillo, Carmine; Tesauro, Manfredi; Panza, Julio A; Campia, Umberto

2015-01-01

Healthy middle-aged postmenopausal women have higher endothelium-dependent dilation and lower vasoconstrictor activity of endothelin-1 than men. Whether these sex-specific differences extend to patients with cardiovascular risk factors has not been investigated. The current study aimed to determine whether, in patients with cardiovascular risk factors, sex-specific differences exist in endothelium-dependent dilation and endothelin-1 activity. Forearm blood flow responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine, sodium nitroprusside, and the selective endothelin type A receptor blocker BQ-123 in 50 women and 64 men with cardiovascular risk factors. Acetylcholine and sodium nitroprusside induced a significant vasodilation in women and men alike (p < 0.01 for both). Also BQ-123 caused a significant vasodilation (p < 0.001) in both groups. The vasodilator response to acetylcholine was greater in women compared to men; however there were no differences in the response to sodium nitroprusside and BQ-123 (p = NS for both) between the two sex groups. Middle-aged women with cardiovascular risk factors have significantly higher endothelium-dependent dilation than middle-aged men; however, vascular endothelin 1 activity is similar in the two groups. These findings suggest that the presence of cardiovascular risk factors is associated with sex-specific effects on endothelium-dependent dilation but not on endothelin 1 activity. Further study is needed to confirm our findings and to characterize the mechanisms underlying this sex-specific regulation of endothelial function.

Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition.

PubMed

Devin, Jessica K; Pretorius, Mias; Nian, Hui; Yu, Chang; Billings, Frederic T; Brown, Nancy J

2014-05-01

Dipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce postprandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme (ACE). During ACE inhibition, substance P is inactivated primarily by dipeptidyl peptidase-4, whereas bradykinin is first inactivated by aminopeptidase P. This study tested the hypothesis that dipeptidyl peptidase-4 inhibition potentiates vasodilator and fibrinolytic responses to substance P when ACE is inhibited. Twelve healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received sitagliptin 200 mg by mouth or placebo. Substance P and bradykinin were infused via brachial artery before and during intra-arterial enalaprilat. Sitagliptin and enalaprilat each reduced forearm vascular resistance and increased forearm blood flow without affecting mean arterial pressure, but there was no interactive effect of the inhibitors. Enalaprilat increased bradykinin-stimulated vasodilation and tissue plasminogen activator release; sitagliptin did not affect these responses to bradykinin. The vasodilator response to substance P was unaffected by sitagliptin and enalaprilat; however, substance P increased heart rate and vascular release of norepinephrine during combined ACE and dipeptidyl peptidase-4 inhibition. In women, sitagliptin diminished tissue plasminogen activator release in response to substance P both alone and during enalaprilat. Substance P increases sympathetic activity during combined ACE and dipeptidyl peptidase-4 inhibition. - URL: http://www.clinicaltrials.gov. Unique identifier: NCT01413542.

Substance P increases Sympathetic Activity during Combined Angiotensin Converting Enzyme and Dipeptidyl Peptidase-4 Inhibition

PubMed Central

Devin, Jessica K.; Pretorius, Mias; Nian, Hui; Yu, Chang; Billings, Frederic T.; Brown, Nancy J.

2014-01-01

Dipeptidyl peptidase-4 inhibitors prevent the degradation of incretin hormones and reduce post-prandial hyperglycemia in patients with type 2 diabetes mellitus. Dipeptidyl peptidase-4 degrades other peptides with a penultimate proline or alanine, including bradykinin and substance P, which are also substrates of angiotensin-converting enzyme. During angiotensin-converting enzyme inhibition, substance P is inactivated primarily by dipeptidyl peptidase-4, while bradykinin is first inactivated by aminopeptidase P. This study tested the hypothesis that dipeptidyl peptidase-4 inhibition potentiates vasodilator and fibrinolytic responses to substance P when angiotensin-converting enzyme is inhibited. Twelve healthy subjects participated in this randomized, double-blinded, placebo-controlled crossover study. On each study day, subjects received sitagliptin 200 mg p.o. or placebo. Substance P and bradykinin were infused via brachial artery before and during intra-arterial enalaprilat. Sitagliptin and enalaprilat each reduced forearm vascular resistance and increased forearm blood flow without affecting mean arterial pressure, but there was no interactive effect of the inhibitors. Enalaprilat increased bradykinin-stimulated vasodilation and tissue plasminogen activator release; sitagliptin did not affect these responses to bradykinin. The vasodilator response to substance P was unaffected by sitagliptin and enalaprilat, however, substance P increased heart rate and vascular release of norepinephrine during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition. In women, sitagliptin diminished tissue plasminogen activator release in response to substance P both alone and during enalaprilat. Substance P increases sympathetic activity during combined angiotensin-converting enzyme and dipeptidyl peptidase-4 inhibition. PMID:24516103

Intra-Arterial Hepatic Chemotherapy: A Comparison of Percutaneous Versus Surgical Implantation of Port-Catheters

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

Deschamps, F., E-mail: frederic.deschamps@igr.fr; Elias, D., E-mail: elias@igr.fr; Goere, D., E-mail: goere@igr.fr

2011-10-15

Purpose: To compare retrospectively the safety and efficacy of percutaneous and surgical implantations of port-catheters for intra-arterial hepatic chemotherapy (IAHC). Materials and Methods: Between January 2004 and December 2008, 126 consecutive patients (mean age 58 years) suffering from liver colorectal metastases were referred for intra-arterial hepatic chemotherapy (IAHC). Port-catheters were percutaneously implanted (P) through femoral access with the patient under conscious sedation when no other surgery was planned or were surgically implanted (S) when laparotomy was performed for another purpose. We report the implantation success rate, primary functionality, functionality after revision, and complications of IAHC. Results: The success rates ofmore » implantation were 97% (n = 65 of 67) for P and 98% (n = 58 of 59) for S. One hundred eleven patients received IAHC in our institution (n = 56P and n = 55S). Primary functionality was the same for P and S (4.80 vs. 4.82 courses), but functionality after revision was significantly higher for P (9.18 vs. 5.95 courses, p = 0.004) than for S. Forty-five complications occurred during 516 courses for P and 28 complications occurred during 331 courses for S. The rates of discontinuation of IAHC linked to complications of the port-catheters were 21% (n = 12 of 56) for P and 34% (n = 19 of 55) for S. Conclusion: Overall, significantly better functionality and similar complication rates occurred after P versus S port-catheters.« less

Factors Contributing to Massive Blood Loss on Peripartum Hysterectomy for Abnormally Invasive Placenta: Who Bleeds More?

PubMed Central

Usui, Rie; Suzuki, Hirotada; Baba, Yosuke

2016-01-01

Introduction. To identify factors that determine blood loss during peripartum hysterectomy for abnormally invasive placenta (AIP-hysterectomy). Methods. We reviewed all of the medical charts of 11,919 deliveries in a single tertiary perinatal center. We examined characteristics of AIP-hysterectomy patients, with a single experienced obstetrician attending all AIP-hysterectomies and using the same technique. Results. AIP-hysterectomy was performed in 18 patients (0.15%: 18/11,919). Of the 18, 14 (78%) had a prior cesarean section (CS) history and the other 4 (22%) were primiparous women. Planned AIP-hysterectomy was performed in 12/18 (67%), with the remaining 6 (33%) undergoing emergent AIP-hysterectomy. Of the 6, 4 (4/6: 67%) patients were primiparous women. An intra-arterial balloon was inserted in 9/18 (50%). Women with the following three factors significantly bled less in AIP-hysterectomy than its counterpart: the employment of an intra-arterial balloon (4,448 ± 1,948 versus 8,861 ± 3,988 mL), planned hysterectomy (5,003 ± 2,057 versus 9,957 ± 4,485 mL), and prior CS (5,706 ± 2,727 versus 9,975 ± 5,532 mL). Patients with prior CS (−) bled more: this may be because these patients tended to undergo emergent surgery or attempted placental separation. Conclusion. Patients with intra-arterial balloon catheter insertion bled less on AIP-hysterectomy. Massive bleeding occurred in emergent AIP-hysterectomy without prior CS. PMID:27630716

Rho-dependent kinase is involved in agonist-activated calcium entry in rat arteries

PubMed Central

Ghisdal, Philippe; Vandenberg, Greet; Morel, Nicole

2003-01-01

The present study was aimed at investigating whether, besides its pivotal role in Ca2+-independent contraction of smooth muscle, Rho-kinase is involved in the mechanisms underlying the Ca2+ signal activated by noradrenaline in arteries. In rat aorta and mesenteric artery, the Rho-kinase inhibitor Y-27632 (10 μM) completely relaxed the contraction evoked by noradrenaline (1 μM) and simultaneously inhibited the Ca2+ signal by 54 ± 1 % (mesenteric artery) and 71 ± 15 % (aorta), and the cell membrane depolarisation by 56 ± 11 % (mesenteric artery). A similar effect was observed in arteries contracted by AlF4−, while in KCl-contracted arteries, Y-27632 decreased tension without changing cytosolic Ca2+. The same effects were observed with another inhibitor of Rho-kinase (HA1077) but not with an inhibitor of protein kinase C (Ro-31–8220). Effects of Y-27632 were not prevented by incubating the artery in 25 mM KCl, with K+ channel blockers or with the Ca2+ channel blocker nimodipine. Y-27632 did not affect either the increase in the production of inositol phosphates activated by noradrenaline, or the release of Ca2+ from non-mitochondrial stores evoked by InsP3 in permeabilised aortic cells, or the Ca2+ signals evoked by thapsigargin or caffeine. The capacitative Ca2+ entry activated by thapsigargin was not impaired by Y-27632, but the entry of Ba2+ activated by noradrenaline in the presence of nimodipine was blocked by 10 μM Y-27632. These results indicate that Rho-kinase is involved in noradrenaline activation of a Ca2+ entry distinct from voltage- or store-operated channels in rat arteries. PMID:12853654

LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

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

Sun Haipeng; Xu Beibei; Sheveleva, Elena

2008-10-01

Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression.more » LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca{sup 2+} concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes.« less

Clinical observation on effect of scalp electroacupuncture for mild cognitive impairment.

PubMed

Zhang, Hong; Zhao, Ling; Yang, Sha; Chen, Zhigang; Li, Yingkun; Peng, Xiaohong; Yang, Yulong; Zhu, Manjia

2013-02-01

To evaluate the therapeutic effect of scalp electroacupuncture for mild cognitive impairment (MCI) in the early stage. Two hundred and thirty three MCI patients were randomly divided into three groups: the drug group, the scalp electroacupuncture group, and the syndrome differentiation group. For the scalp electroacupuncture group, the points of Baihui (DU 20), Sishecong (EX-HN1), Fengchi (GB 20), and Shenting (DU 24) were selected. For the syndrome differentiation group, specific acupoints were added on the basis of syndrome differentiation and according to the scale for the differentiation of syndromes in vascular dementia (SDSVD) beside the acupoints used in the scalp electroacupuncture group. For the drug group, nimodipine was orally administered. Each patient was treated for two courses, eight weeks. The score differences in mini-mental state examination (MMSE), picture recognition, and clock drawing test were observed before and after the treatment. After treatment, the score differences in MMSE and clock drawing test were of obvious statistical significance among three groups (P < 0.01, P < 0.05). The score differences in picture recognition were of extremely statistical significance between the scalp electroacupuncture group and the syndrome differentiation group (P < 0.01), while the difference was not found in the drug group (P > 0.05). There were statistical significant differences in therapeutic effects between the scalp electroacupuncture group and the drug group, and between the syndrome differentiation group and the drug group (P < 0.05), while no statistical difference was found between scalp electroacupuncture group and the syndrome differentiation group (P > 0.05). All the three therapies may improve the cognitive function of MCI patients. The therapeutic effects in the scalp electroacupuncture and syndrome differentiation groups were basically the same, but superior to nimodipine.

Reduced levels of Cacna1c attenuate mesolimbic dopamine system function.

PubMed

Terrillion, C E; Dao, D T; Cachope, R; Lobo, M K; Puche, A C; Cheer, J F; Gould, T D

2017-06-01

Genetic variation in CACNA1C, which codes for the L-type calcium channel (LTCC) Ca v 1.2, is associated with clinical diagnoses of bipolar disorder, depression and schizophrenia. Dysregulation of the mesolimbic-dopamine (ML-DA) system is linked to these syndromes and LTCCs are required for normal DAergic neurotransmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc). It is unclear, however, how variations in CACNA1C genotype, and potential subsequent changes in expression levels in these regions, modify risk. Using constitutive and conditional knockout mice, and treatment with the LTCC antagonist nimodipine, we examined the role of Cacna1c in DA-mediated behaviors elicited by psychomotor stimulants. Using fast-scan cyclic voltammetry, DA release and reuptake in the NAc were measured. We find that subsecond DA release in Cacna1c haploinsufficient mice lacks normal sensitivity to inhibition of the DA transporter (DAT). Constitutive haploinsufficiency of Cacna1c led to attenuation of hyperlocomotion following acute administration of stimulants specific to DAT, and locomotor sensitization of these mice to the DAT antagonist GBR12909 did not reach the same level as wild-type mice. The maintenance of sensitization to GBR12909 was attenuated by administration of nimodipine. Sensitization to GBR12909 was attenuated in mice with reduced Cacna1c selectively in the VTA but not in the NAc. Our findings show that Cacna1c is crucial for normal behavioral responses to DA stimulants and that its activity in the VTA is required for behavioral sensitization. Cacna1c likely exerts these effects through modifications to presynaptic ML-DA system function. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Resveratrol-induced antinociception is involved in calcium channels and calcium/caffeine-sensitive pools.

PubMed

Pan, Xiaoyu; Chen, Jiechun; Wang, Weijie; Chen, Ling; Wang, Lin; Ma, Quan; Zhang, Jianbo; Chen, Lichao; Wang, Gang; Zhang, Meixi; Wu, Hao; Cheng, Ruochuan

2017-02-07

Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) levels in the spinal cord were also investigated when treated with the above drugs. The results showed that resveratrol increased the tail flick latency in the tail-flick test, in dose-dependent manner. N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK 801 potentiated the antinociceptive effects of sub-threshold dose of resveratrol at 10 mg/kg. Ca2+ channel blocker, however, abolished the antinociceptive effects of resveratrol. In contrast to these results, EGTA or ryanodine treatment (i.c.v.) potentiated resveratrol-induced antinociception. There was a significant decrease in p-CaMKII and an increase in BDNF expression in the spinal cord when combined with MK 801, nimodipine, ryanodine and EGTA. While an increase in p-CaMKII level and a decrease in BDNF expression were observed when high dose of resveratrol combined with CaCl2. These findings suggest that resveratrol exhibits the antinociceptive effects by inhibition of calcium channels and calcium/caffeine-sensitive pools.

Postoperative Cerebral Vasospasm Following Transsphenoidal Pituitary Adenoma Surgery.

PubMed

Eseonu, Chikezie I; ReFaey, Karim; Geocadin, Romergryko G; Quinones-Hinojosa, Alfredo

2016-08-01

Cerebral vasospasm following a transsphenoidal resection of a pituitary adenoma is a devastating occurrence that can lead to delayed cerebral ischemia and poor neurologic outcome if not diagnosed and treated in a timely manner. The etiology of this condition is not well understood but can lead to significant arterial vasospasm that causes severe ischemic insults. In this paper, we identify common presenting symptoms and essential management strategies to treat this harmful disease. A retrospective case report and literature review of presentation, treatment, and outcome of cerebral vasospasm following transsphenoidal surgery. We present 1 case and review 12 known cases in the literature on vasospasm following transsphenoidal surgery. Mean age was 48 (±13.8) years. There were 46.2% male patients. Factors associated with vasospasm, such as cerebral spinal fluid leaks following surgery, were seen in 38.5% of cases, and postoperative subarachnoid hemorrhage (SAH) was seen in 84.6% of cases. Hemiparesis was the presenting symptom of delayed cerebral ischemia in 61.5% of cases. For management, maintaining at least a euvolemic volume status was used in 76.9%, induced hypertension was used in 61.5%, and nimodipine was administered in 46.2% of cases. Patients returned to their neurologic baseline in 61.5% of cases, had new permanent deficits in 7.7% of cases, and died in 30.8% of cases. Cerebral vasospasm following transsphenoidal surgery is a dangerous disease that can lead to a high likelihood of mortality if not identified and treated. Early postoperative events, such as peritumoral subarachnoid hemorrhage and hemiparesis, may be factors associated with post-transsphenoidal surgery vasospasm. Effective treatment options used in patients that regained complete neurologic recovery were by inducing hypertension, maintaining euvolemia, and administering nimodipine. Copyright © 2016 Elsevier Inc. All rights reserved.

Arterial imaging in patients with lower extremity ischemia and diabetes mellitus.

PubMed

Pomposelli, Frank

2010-09-01

Precise, comprehensive imaging of the arterial circulation is the cornerstone of successful revascularization of the ischemic extremity in patients with diabetes mellitus. Arterial imaging is challenging in these patients because the disease is often multisegmental with a predilection for the distal tibial and peroneal arteries. Occlusive lesions and the arterial wall itself are often calcified and patients presenting with ischemic complications frequently have underlying renal insufficiency. Intra-arterial digital subtraction angiography (DSA), contrast enhanced magnetic resonance angiography (MRA), and more recently, computerized tomographic angiography (CTA) have been used as imaging modalities in lower extremity ischemia. Each has specific advantages and shortcomings in this patient population, which will be summarized and contrasted in this review. DSA is an invasive technique most often performed from a femoral arterial puncture and requires the injection of arterial contrast, which can occasionally cause allergic reactions. In patients with pre-existing renal insufficiency, contrast infusion can result in worsening renal failure; although usually self-limited, it may occasionally require hemodialysis, especially in patients with diabetes. However, DSA provides the highest degree of spatial resolution and image quality. It is also the only modality in which the diagnosis and treatment of arterial disease can be performed simultaneously. MRA is noninvasive, and when enhanced with gadolinium contrast injection provides arterial images of comparable quality to DSA and in some circumstances may uncover distal arterial targets not visualized on DSA. However, spatial resolution is inferior to DSA and erroneous interpretations due to acquisition artifacts are common. Specialized equipment and imaging techniques are necessary to minimize their occurrence in the distal lower extremity. In addition, due to the risk of inducing nephrogenic systemic fibrosis, gadolinium-enhanced MRA cannot be used in patients with renal insufficiency. CTA is noninvasive and rapidly performed, with better spatial resolution than MRA, but requires the largest volume of contrast infusion, exposes patients to high-doses of radiation, and is subject to interpretive error due to reconstruction artifacts especially in heavily calcified arteries, limiting its usefulness in many patients with diabetes. For patients in whom the planned intervention is a surgical bypass, DSA and MRA will provide high quality images of the lower extremity arterial anatomy. For patients in whom a catheter-based intervention is the likely treatment, a diagnostic DSA immediately followed by a catheter-based treatment in the same procedure is the preferred approach. In patients with pre-existing renal dysfunction, in which gadolinium-enhanced MRA is contraindicated, DSA or CTA can be performed. However, patients should have an infusion of intravenous normal saline solution or sodium bicarbonate before the procedure to reduce the incidence of contrast-induced nephropathy. Copyright © 2010. Published by Mosby, Inc.

Long-term results of intra-arterial onyx injection for type II endoleaks following endovascular aneurysm repair.

PubMed

Ribé, L; Bicknell, C D; Gibbs, R G; Burfitt, N; Jenkins, M P; Cheshire, N; Hamady, M

2017-06-01

Purpose The aim of this paper is to report our experience of type II endoleak treatment after endovascular aneurysm repair with intra-arterial injection of the embolizing liquid material, Onyx liquid embolic system. Methods From 2005 to 2012, we performed a retrospective review of 600 patients, who underwent endovascular repair of an abdominal aortic aneurysm. During this period, 18 patients were treated with Onyx for type II endoleaks. Principal findings The source of the endoleak was the internal iliac artery in seven cases, inferior mesenteric artery in seven cases and lumbar arteries in four cases. Immediate technical success was achieved in all patients and no endoleak from the treated vessel recurred. During a mean follow-up of 19 months, no major morbidity or mortality occurred, and one-year survival was 100%. Conclusions Treatment of type II endoleaks with Onyx is safe and effective over a significant time period.

Intra-arterial brachytherapy of hepatic malignancies: watch the flow.

PubMed

Morgan, Bruno; Kennedy, Andrew S; Lewington, Val; Jones, Bleddyn; Sharma, Ricky A

2011-02-01

Although the liver possesses a dual blood supply, arterial vessels deliver only a small proportion of blood to normal parenchyma, but they deliver the vast majority of blood to primary and secondary cancers of the liver. This anatomical discrepancy is the basis for intra-arterial brachytherapy of liver cancers using radioactive microspheres, termed radio-embolization (RE). Radioactive microspheres implant preferentially in the terminal arterioles of tumors. Although biological models of the flow dynamics and distribution of microspheres are currently in development, there is a need to improve the imaging biomarkers of flow dynamics used to plan RE. Since a direct consequence of RE is vascular disruption and necrosis, we suggest that imaging protocols sensitive to changes in vasculature are highly likely to represent useful early biomarkers for treatment efficacy. We propose dynamic contrast-enhanced CT as the most appropriate imaging modality for studying vascular parameters in clinical trials of RE treatment.

Comparative survival analysis of adjuvant therapy with iodine-131-labeled lipiodol to hepatic resection of primary hepatocellular carcinoma: a meta-analysis.

PubMed

Gong, Lin; Shi, Lu; Sun, Jing; Yuan, Wei-Sheng; Chen, Jian-Feng; Liu, Peng; Gong, Feng; Dong, Jia-Hong

2014-05-01

Adjuvant therapies play an important role in delaying the recurrence of hepatocellular carcinoma (HCC) in patients with resectable tumor. Among the available options, use of radionuclides is an effective strategy. This meta-analysis aims to examine the evidence pertaining to the effectiveness of adjuvant therapy with intra-arterial iodine-131-labeled lipiodol ((131)I-lipiodol) to hepatic resection of HCC. A literature survey was conducted of multiple electronic databases including PubMed/Medline, Embase, CINAHL, Cochrane library, and Google Scholar using various combinations of the most relevant key terms. The odds ratio-based meta-analysis of recurrence and survival rates was performed with RevMan software (version 5.2) using a random-effect model. Heterogeneity was assessed by χ(2) and I(2) statistics. When compared with the resection-only group, recurrence rates at 2 and 5 years were significantly lower in patients who received adjuvant therapy with intra-arterial I-lipiodol, with a corresponding odds ratio (95% confidence interval) of 0.45 (0.29-0.70) and 0.52 (0.32-0.85), respectively. The 3- and 5-year overall survival rates were found to be significantly higher in patients who received adjuvant therapy with (131)I-lipiodol than in patients who were not given any adjuvant therapy. Between-study statistical heterogeneity was moderate. Postoperative adjuvant therapy with intra-arterial (131)I-lipiodol to hepatic resection of HCC significantly improves overall and disease-free survival rates and reduces recurrence rates. However, well-designed randomized trials are needed to arrive at conclusive evidence.

FEASIBILITY AND SAFETY OF CONTRAST-ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES.

PubMed

Seiler, Gabriela S; Campbell, Nigel; Nixon, Britton; Tsuruta, James K; Dayton, Paul A; Jennings, Samuel; Redding, W Rich; Lustgarten, Meghann

2016-05-01

Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra-arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra-arterial injections. Intra-arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases. © 2016 American College of Veterinary Radiology.

Assessment of renal vasoconstriction in vivo after intra-arterial administration of the isosmotic contrast medium iodixanol compared to the low-osmotic contrast medium iopamidol.

PubMed

Treitl, Marcus; Rupprecht, Harald; Wirth, Stefan; Korner, Markus; Reiser, Maximilian; Rieger, Johannes

2009-05-01

Low-osmotic contrast media (LOCM) such as iopamidol are known to increase the renal resistance index (RRI). The aim of our study was to evaluate in vivo the different effects of intra-arterial administration of LOCM in comparison to isosmotic contrast medium (IOCM) such as iodixanol on the human RRI. Twenty patients (16 males, 4 females; 66 years on average) with normal renal function (mean creatinine 1.0 mg/dl) had digital subtraction angiography (DSA) of the abdominal and lower-limb arteries. Ten patients received LOCM, and 10 patients IOCM (150 ml on average, 20 ml/s). The RRI was assessed by an experienced nephrologist with duplex ultrasound from 15 min before until 30 min after the first injection with delays of 1-5 min. The basic value of the RRI and differential RRI were calculated. The basic value of the RRI was 0.69 in the LOCM group and 0.71 in the IOCM group. After LOCM a significant increase of the RRI to 0.73 on average (P < or = 0.001) 2 min after the first injection was found, whereas IOCM did not result in a significant change of the RRI (RRI remained 0.71 on average, P > or = 0.1). In the LOCM group, the RRI returned to the basic value after 30 min (+/-2.3 min). Intra-arterial administration of IOCM had no influence on renal vascular resistance as expressed by the RRI, unlike LOCM, which induced a highly significant increase of the RRI for up to 30 min.

Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke

PubMed Central

Bentley, Paul; Hamady, Mohammad; Marley, Stephen; Davis, John; Shlebak, Abdul; Nicholls, Joanna; Williamson, Deborah A.; Jensen, Steen L.; Gordon, Myrtle; Habib, Nagy; Chataway, Jeremy

2014-01-01

Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra-arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open-label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty-two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age >80 years (n = 19); medical instability (n = 17), and significant carotid stenosis (n = 13). The procedure was well tolerated in all patients, and no significant treatment-related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6-month follow-up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials. PMID:25107583

Quality of life after intra-arterial treatment for acute ischemic stroke in the MR CLEAN trial-Update.

PubMed

Schreuders, Jennifer; van den Berg, Lucie A; Fransen, Puck Ss; Berkhemer, Olvert A; Beumer, Debbie; Lingsma, Hester F; van Oostenbrugge, Robert J; van Zwam, Wim H; Majoie, Charles Blm; van der Lugt, Aad; de Kort, Paul Lm; Roos, Yvo Bwem; Dippel, Diederik Wj

2017-10-01

Background Health-related quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire was one of the secondary outcomes in the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN). We reported no statistically significant difference in EuroQol Group 5-Dimension Self-Report Questionnaire score between the intervention and control groups, but deaths were not included. Aims Reanalyze the effect of intra-arterial treatment for large vessel occlusion in acute ischemic stroke patients on health-related quality of life in more detail. We now include patients who died during follow-up. Methods The EuroQol Group 5-Dimension Self-Report Questionnaire questionnaires were obtained 90 days after treatment. We used the Dutch tariff to derive a utility index from the EuroQol Group 5-Dimension Self-Report Questionnaire score. Treatment effect was estimated with the Mann-Whitney U test and linear regression. The effect of treatment on the distribution of EuroQol Group 5-Dimension Self-Report Questionnaire dimension scores was assessed with ordinal logistic regression. Results We obtained EuroQol Group 5-Dimension Self-Report Questionnaire scores from 457 (91.7%) of the 500 patients, including 108 who died before follow-up. Median EuroQol Group 5-Dimension Self-Report Questionnaire score in the intervention group was 0.57, and 0.39 in the control group (p = 0.03). Treatment effect estimated with linear regression was 0.07 (95%CI: -0.001 to 0.143). Treatment specifically affected EuroQol Group 5-Dimension Self-Report Questionnaire dimensions "mobility" (OR: 0.43, 95%CI: 0.29-0.66), "self-care" (OR: 0.60, 95%CI: 0.41-0.89), and "usual activities" (OR: 0.53, 95%CI: 0.36-0.79). Conclusion Treatment had a limited effect on quality of life, as measured with the EuroQol Group 5-Dimension Self-Report Questionnaire. Nevertheless, patients with acute ischemic stroke caused by an intracranial occlusion in the anterior circulation, who had intra-arterial treatment, experience better health-related quality of life than patients without intra-arterial treatment. Trial Registration URL: http://www.isrctn.com/ISRCTN10888758 Unique identifier: ISRCTN10888758.

Toxicokinetics of perfluorooctane sulfonate in rainbow trout (Oncorhynchus mykiss)

EPA Science Inventory

Rainbow trout (Oncorhynchus mykiss) confined to respirometer-metabolism chambers were dosed with perfluorooctane sulfonate (PFOS) by intra-arterial injection and sampled to obtain concentration time-course data for plasma, and either urine or expired water. The data were then an...

The in vivo pharmacology of CP-80, 633, a selective inhibitor of phosphodiesterase 4.

PubMed

Turner, C R; Cohan, V L; Cheng, J B; Showell, H J; Pazoles, C J; Watson, J W

1996-09-01

The following studies were conducted to characterize the bron-chodilatory and antiinflammatory activity of the novel, selective phosphodiesterase-IV inhibitor, CP-80,633 (2'S)5-[3-(2'-exobicyclo[2.2.1]heptyloxy-4-methoxy-phenyl]te trahydro- 2(1H)-pyrimidone, a compound in clinical development for atopic disease. In IgG1 passively sensitized guinea pigs, aerosolized ovalbumin challenge increases both pulmonary eosinophil peroxidase levels and airway obstruction. CP-80,633, administered before ovalbumin challenge, significantly attenuated both the increase in tissue eosinophil peroxidase levels (ED50 = 1.4 mg/kg, p.o.) and airway obstruction (ED50 = 0.93 +/- 0.14 mg/kg,p.o.) 10 to 30 times more potently than theophyl-line. Intraarterially administered CP-80,633 also reversed an established bronchoconstriction initiated by continuous infusion of histamine to guinea pigs (ED50 of 8.2 micrograms/kg vs. 5.6 mg/kg for theophylline). The antiinflammatory effect of CP-80,633 was also examined in atopic monkeys challenged with Ascaris suum (Ag) aerosol. CP-80,633 (1 mg/kg, qid, s.c., 1 hr before antigen challenge) significantly reduced antigen-induced increases in bronchoalveolar lavage neutrophils (72.8 +/- 15.8% inhibition) and eosinophils (61.1 +/- 5.7% inhibition) 4 hr postchallenge, but did not reduce leukocytes 24 hr postchallenge. CP-80,633 did not inhibit antigen-induced increases in BAL levels of interleukin-1 beta, -6 or -8 as measured by enzyme-linked immunosorbant assay. These results indicate that CP-80,633 possesses bronchodilatory activity in guinea pigs and some antiinflammatory effects in both guinea pigs and monkeys.

The right intercostobronchial trunk: anatomical study in respect of posterior intercostal artery origin and its clinical application.

PubMed

Kocbek, Lidija; Rakuša, Mateja

2018-01-01

The right bronchial artery usually arises from the descending thoracic aorta as a common trunk with the right intercostal artery and forms the right intercostobronchial trunk. Both, the third right posterior intercostal artery and the right intercostobronchial trunk, are described as the most constant vessels. The focus of the study was to determine the characteristics of the right intercostobronchial trunk regarding the origins of the posterior intercostal arteries from the thoracic aorta. Posterior intercostal arteries and the right bronchial arteries were dissected in 43 human cadavers, preserved after Thiel's embalming method with intraarterial infusion of red colored latex. Postmortem examination gave valued information on the right intercostobronchial trunk present in 58% of cases. The right intercostobronchial trunk was mapped and new classification regarding the origin of the posterior intercostal arteries from the thoracic aorta suggested type A, B and C, the latter ones into subtypes 1 and 2. Type A was proportional to the origin level of the PIA and its corresponding intercostal space. Size of outer diameter at the origin did not indicate the right bronchial artery branch. In subtype 2 of type B the proximal posterior intercostal artery diameter that gave off right bronchial artery was thicker than distal one. The right bronchial artery originates from the second to the fifth posterior intercostal artery forming the right intercostobronchial trunk. Various origin and types of origin, diameter and course of the right intercostobronchial trunk described and analyzed in the study offer valuable information on the procedures involving the right intercostobronchial trunk.

Adoptive cell transfer after chemotherapy enhances survival in patients with resectable HNSCC.

PubMed

Jiang, Pan; Zhang, Yan; J Archibald, Steve; Wang, Hua

2015-09-01

The aims of this study were to evaluate the therapeutic efficacy and to determine the immune factors for treatment success in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemotherapy followed by adoptive cell transfer (ACT). A total of 43 HNSCC patients who received radical resection and chemotherapy were analysed in this study. Twenty-one of the patients were repeatedly treated with ACT after chemotherapy (ACT group), and the other twenty-two patients without ACT treatment were included as part of the control group. To investigate the immunological differences underlying these observations, we expanded and profiled improving cytokine-induced killer cells (iCIK) from peripheral blood mononuclear cells (PBMCs) with the timed addition of RetroNectin, OKT3 mAb, IFN γ and IL-2. The median of progression-free survival (PFS) and overall survival (OS) in the ACT group were significantly higher as compared to the control group (56 vs. 40; 58 vs. 45 months). In iCIK culture, there was a significant reduction in CD3+CD4+ T-cell proliferation and cytokines (IL-2, TNF) production from patients who received chemotherapy compared to patients without chemotherapy. Intra-arterial infusion of iCIK, in coordination with chemotherapy, considerably rescued iCIK culture from the suppression of systemic immunity induced by chemotherapy and induced tumour regression. Altogether, these findings suggest that ACT is an effective neo-adjuvant therapy for rescuing systemic immune suppression and improving survival time in patients with HNSCC. Copyright © 2015 Elsevier B.V. All rights reserved.

Milrinone and homeostasis to treat cerebral vasospasm associated with subarachnoid hemorrhage: the Montreal Neurological Hospital protocol.

PubMed

Lannes, Marcelo; Teitelbaum, Jeanne; del Pilar Cortés, Maria; Cardoso, Mauro; Angle, Mark

2012-06-01

For the treatment of cerebral vasospasm, current therapies have focused on increasing blood flow through blood pressure augmentation, hypervolemia, the use of intra-arterial vasodilators, and angioplasty of proximal cerebral vessels. Through a large case series, we present our experience of treating cerebral vasospasm with a protocol based on maintenance of homeostasis (correction of electrolyte and glucose disturbances, prevention and treatment of hyperthermia, replacement of fluid losses), and the use of intravenous milrinone to improve microcirculation (the Montreal Neurological Hospital protocol). Our objective is to describe the use milrinone in our practice and the neurological outcomes associated with this approach. Large case series based on the review of all patients diagnosed with delayed ischemic neurologic deficits after aneurysmal subarachnoid hemorrhage between April 1999 and April 2006. 88 patients were followed for a mean time of 44.6 months. An intravenous milrinone infusion was used for a mean of 9.8 days without any significant side effects. No medical complications associated with this protocol were observed. There were five deaths; of the surviving patients, 48.9 % were able to go back to their previous baseline and 75 % had a good functional outcome (modified Rankin scale ≤ 2). A protocol using intravenous milrinone, and the maintenance of homeostasis is simple to use and requires less intensive monitoring and resources than the standard triple H therapy. Despite the obvious limitations of this study's design, we believe that it would be now appropriate to proceed with formal prospective studies of this protocol.

Neural control of blood flow during exercise in human metabolic syndrome.

PubMed

Limberg, Jacqueline K; Morgan, Barbara J; Sebranek, Joshua J; Proctor, Lester T; Eldridge, Marlowe W; Schrage, William G

2014-09-01

α-Adrenergic-mediated vasoconstriction is greater during simulated exercise in animal models of metabolic syndrome (MetSyn) when compared with control animals. In an attempt to translate such findings to humans, we hypothesized that adults with MetSyn (n = 14, 35 ± 3 years old) would exhibit greater α-adrenergic responsiveness during exercise when compared with age-matched healthy control subjects (n = 16, 31 ± 3 years old). We measured muscle sympathetic nerve activity (MSNA; microneurography) and forearm blood flow (Doppler ultrasound) during dynamic forearm exercise (15% of maximal voluntary contraction). α-Adrenergic agonists (phenylephrine and clonidine) and an antagonist (phentolamine) were infused intra-arterially to assess α-adrenergic receptor responsiveness and restraint, respectively. Resting MSNA was ∼35% higher in adults with MetSyn (P < 0.05), but did not change in either group with dynamic exercise. Clonidine-mediated vasoconstriction was greater in adults with MetSyn (P < 0.01). Group differences in vascular responses to phenylephrine and phentolamine were not detected (P > 0.05). Interestingly, exercise-mediated vasodilatation was greater in MetSyn (P < 0.05). Adults with MetSyn exhibit greater resting MSNA and clonidine-mediated vasoconstriction, yet preserved functional sympatholysis and higher exercise blood flow during low-intensity hand-grip exercise when compared with age-matched healthy control subjects. These results suggest that adults with MetSyn exhibit compensatory vascular control mechanisms capable of preserving blood flow responses to exercise in the face of augmented sympathetic adrenergic activity. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Oxidative stress exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation in rats with hypertension induced by angiotensin II.

PubMed

Koba, Satoshi; Watanabe, Ryosuke; Kano, Naoko; Watanabe, Tatsuo

2013-01-01

Muscle contraction stimulates thin fiber muscle afferents and evokes reflex sympathoexcitation. In hypertension, this reflex is exaggerated. ANG II, which is elevated in hypertension, has been reported to trigger the production of superoxide and other reactive oxygen species. In the present study, we tested the hypothesis that increased ANG II in hypertension exaggerates skeletal muscle contraction-evoked reflex sympathoexcitation by inducing oxidative stress in the muscle. In rats, subcutaneous infusion of ANG II at 450 ng·kg(-1)·min(-1) for 14 days significantly (P < 0.05) elevated blood pressure compared with sham-operated (sham) rats. Electrically induced 30-s hindlimb muscle contraction in decerebrate rats with hypertension evoked larger renal sympathoexcitatory and pressor responses [+1,173 ± 212 arbitrary units (AU) and +35 ± 5 mmHg, n = 10] compared with sham normotensive rats (+419 ± 103 AU and +13 ± 2 mmHg, n = 11). Tempol, a SOD mimetic, injected intra-arterially into the hindlimb circulation significantly reduced responses in hypertensive rats, whereas this compound had no effect on responses in sham rats. Tiron, another SOD mimetic, also significantly reduced reflex renal sympathetic and pressor responses in a subset of hypertensive rats (n = 10). Generation of muscle superoxide, as evaluated by dihydroethidium staining, was increased in hypertensive rats. RT-PCR and immunoblot experiments showed that mRNA and protein for gp91(phox), a NADPH oxidase subunit, in skeletal muscle tissue were upregulated in hypertensive rats. Taken together, hese results suggest that increased ANG II in hypertension induces oxidative stress in skeletal muscle, thereby exaggerating the muscle reflex.

Role of aldehyde dehydrogenase in hypoxic vasodilator effects of nitrite in rats and humans

PubMed Central

Arif, Sayqa; Borgognone, Alessandra; Lin, Erica Lai-Sze; O'Sullivan, Aine G; Sharma, Vishal; Drury, Nigel E; Menon, Ashvini; Nightingale, Peter; Mascaro, Jorge; Bonser, Robert S; Horowitz, John D; Feelisch, Martin; Frenneaux, Michael P; Madhani, Melanie

2015-01-01

Background and Purpose Hypoxic conditions favour the reduction of nitrite to nitric oxide (NO) to elicit vasodilatation, but the mechanism(s) responsible for bioconversion remains ill defined. In the present study, we assess the role of aldehyde dehydrogenase 2 (ALDH2) in nitrite bioactivation under normoxia and hypoxia in the rat and human vasculature. Experimental Approach The role of ALDH2 in vascular responses to nitrite was studied using rat thoracic aorta and gluteal subcutaneous fat resistance vessels from patients with heart failure (HF; 16 patients) in vitro and by measurement of changes in forearm blood flow (FBF) during intra-arterial nitrite infusion (21 patients) in vivo. Specifically, we investigated the effects of (i) ALDH2 inhibition by cyanamide or propionaldehyde and the (ii) tolerance-independent inactivation of ALDH2 by glyceryl trinitrate (GTN) on the vasodilator activity of nitrite. In each setting, nitrite effects were measured via evaluation of the concentration–response relationship under normoxic and hypoxic conditions in the absence or presence of ALDH2 inhibitors. Key Results Both in rat aorta and human resistance vessels, dilatation to nitrite was diminished following ALDH2 inhibition, in particular under hypoxia. In humans there was a non-significant trend towards attenuation of nitrite-mediated increases in FBF. Conclusions and Implications In human and rat vascular tissue in vitro, hypoxic nitrite-mediated vasodilatation involves ALDH2. In patients with HF in vivo, the role of this enzyme in nitrite bioactivation is at the most, modest, suggesting the involvement of other more important mechanisms. PMID:25754766

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

Kamitani, Takeshi, E-mail: kamitani@radiol.med.kyushu-u.ac.jp; Kawanami, Satoshi, E-mail: kawanami-01@mac.com; Asayama, Yoshiki, E-mail: asayama@radiol.med.kyushu-u.ac.jp

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 LAmore » 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.« less

The Effect of Short-term Intra-arterial Delivery of Paclitaxel on Neointimal Hyperplasia and the Local Thrombotic Environment after Angioplasty

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

Yajun, E, E-mail: eyj7681@yahoo.com.cn; He Nengshu, E-mail: eyajun@hotmail.com; Fan Hailun, E-mail: mydream510@yahoo.com.cn

2013-08-01

PurposeTo evaluate the effects of short-term intra-arterial delivery of paclitaxel on neointimal hyperplasia and the local thrombotic environment after angioplasty.MethodsAn experimental common carotid artery injury model was established in 60 rats, which were divided into experimental groups (40 rats) and controls (20 rats). Local intra-arterial administration of paclitaxel was applied at 2 doses (90 and 180 {mu}g/30 {mu}l), and the effects of short-term delivery of paclitaxel on neointimal hyperplasia and the expression of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated at days 15 and 30 by hematoxylin and eosin staining and immunohistochemistry.ResultsAt 15more » and 30 days after injury, neointimal thickness and area, the ratio of intimal area to medial area and the stenotic rate were all significantly decreased in the group provided the high concentrations (180 {mu}g/30 {mu}l) of paclitaxel for 2 min or 10 min and in the group provided the low concentration (90 {mu}g/30 {mu}l) of paclitaxel for 10 min (p < 0.05). At 30 days after injury, there were no significant changes in TF expression among all experimental groups. PAI-1 expression increased in the neointima of the high concentration 10 min group (p < 0.05), while t-PA expression decreased in the neointima of the high concentration 2 min group (p < 0.05).ConclusionIn the rat common carotid artery injury model, the short-term delivery of paclitaxel could effectively inhibit neointimal hyperplasia in the long term, with very little influence on the local expression of TF and PAI-1.« less

Penetration of intra-arterially administered vincristine in experimental brain tumor1,2

PubMed Central

Boyle, Frances M.; Eller, Susan L.; Grossman, Stuart A.

2004-01-01

Vincristine is an integral part of the “PCV” regimen that is commonly administered to treat primary brain tumors. The efficacy of vincristine as a single agent in these tumors has been poorly studied. This study was designed to determine whether vincristine enters normal rat brain or an intracranially or subcutaneously implanted glioma and to assess the presence of the efflux pump P-glycoprotein (P-gp) on tumor and vascular endothelial cells. The 9L rat gliosarcoma was implanted intracranially and subcutaneously in three Fischer 344 rats. On day 7, [3H]vincristine (50 μCi, 4.8 μg) was injected into the carotid artery, and the animals were euthanized 10 or 20 min later. Quantitative autoradiography revealed that vincristine levels in the liver were 6- to 11-fold greater than in the i.c. tumor, and 15- to 37-fold greater than in normal brain, the reverse of the expected pattern with intra-arterial delivery. Vincristine levels in the s.c. tumor were 2-fold higher than levels in the i.c. tumor. P-gp was detected with JSB1 antibody in vascular endothelium of both normal brain and the i.c. tumor, but not in the tumor cells in either location, or in endothelial cells in the s.c. tumor. These results demonstrate that vincristine has negligible penetration of normal rat brain or i.c. 9L glioma despite intra-arterial delivery and the presence of blood-brain barrier dysfunction as demonstrated by Evan’s blue. Furthermore, this study suggests that P-gp-mediated efflux from endothelium may explain these findings. The lack of penetration of vincristine into brain tumor and the paucity of single-agent activity studies suggest that vincristine should not be used in the treatment of primary brain tumors. PMID:15494097

Pedal angiography in peripheral arterial occlusive disease: first-pass i.v. contrast-enhanced MR angiography with blood pool contrast medium versus intraarterial digital subtraction angiography.

PubMed

Kos, Sebastian; Reisinger, Clemens; Aschwanden, Markus; Bongartz, Georg M; Jacob, Augustinus L; Bilecen, Deniz

2009-03-01

The purpose of this study was to prospectively evaluate first-pass i.v. gadofosveset-enhanced MR angiography in patients with peripheral arterial occlusive disease for visualization of the pedal arteries and stenosis or occlusion of those arteries with intraarterial digital subtraction angiography as the reference standard. Twenty patients with peripheral arterial occlusive disease (nine women, 11 men; age-range 58-83 years) were prospectively enrolled. Gadofosveset first-pass contrast-enhanced MR angiography was performed with a 1.5-T system, a dedicated foot coil, and cuff compression to the calf. Arterial segments were assessed for degree of arterial stenosis, arterial visibility, diagnostic utility, and venous contamination. Detection of vessel stenosis or occlusion was evaluated in comparison with findings at digital subtraction angiography. The unpaired Student's t test was used to test arterial visibility with the two techniques. First-pass MR angiography with gadofosveset had good diagnostic utility in 83.9% of all segments and no venous contamination in 96.8% of all segments. There was no difference between the performance of intraarterial digital subtraction angiography and that of i.v. contrast-enhanced MR angiography in arterial visibility overall (p = 0.245) or in subgroup analysis of surgical arterial bypass targets (p = 0.202). The overall sensitivity, specificity, and accuracy of i.v. gadofosveset-enhanced MR angiography for characterization of clinically significant stenosis and occlusion were 91.4%, 96.1%, and 93.9%. In the subgroup analysis, the sensitivity, specificity, and accuracy were 85.5%, 96.5%, and 92.1%. Gadofosveset-enhanced MR angiography of the pedal arteries in patients with peripheral arterial occlusive disease has arterial visibility equal to that of digital subtraction angiography and facilitates depiction of clinically significant stenosis and occlusion.

Value of Computed Tomographic Perfusion-Based Patient Selection for Intra-Arterial Acute Ischemic Stroke Treatment.

PubMed

Borst, Jordi; Berkhemer, Olvert A; Roos, Yvo B W E M; van Bavel, Ed; van Zwam, Wim H; van Oostenbrugge, Robert J; van Walderveen, Marianne A A; Lingsma, Hester F; van der Lugt, Aad; Dippel, Diederik W J; Yoo, Albert J; Marquering, Henk A; Majoie, Charles B L M

2015-12-01

The utility of computed tomographic perfusion (CTP)-based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in randomized trials and requires further study in a cohort that was not selected based on CTP. Our objective was to study the relationship between CTP-derived parameters and outcome and treatment effect in patients with acute ischemic stroke because of a proximal intracranial arterial occlusion. We included 175 patients who underwent CTP in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN). Association of CTP-derived parameters (ischemic-core volume, penumbra volume, and percentage ischemic core) with outcome was estimated with multivariable ordinal logistic regression as an adjusted odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale. Interaction between CTP-derived parameters and treatment effect was determined using multivariable ordinal logistic regression. Interaction with treatment effect was also tested for mismatch (core <70 mL; penumbra core >1.2; penumbra core >10 mL). The adjusted odds ratio for improved functional outcome for ischemic core, percentage ischemic core, and penumbra were 0.79 per 10 mL (95% confidence interval: 0.71-0.89; P<0.001), 0.82 per 10% (95% confidence interval: 0.66-0.90; P=0.002), and 0.97 per 10 mL (96% confidence interval: 0.92-1.01; P=0.15), respectively. No significant interaction between any of the CTP-derived parameters and treatment effect was observed. We observed no significant interaction between mismatch and treatment effect. CTP seems useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from intra-arterial therapy. © 2015 American Heart Association, Inc.

Radiation exposure and radiation protection of the physician in iodine-131 Lipiodol therapy of liver tumours.

PubMed

Risse, J H; Ponath, C; Palmedo, H; Menzel, C; Grünwald, F; Biersack, H J

2001-07-01

Intra-arterial iodine-131 labelled Lipiodol therapy for liver cancer has been investigated for safety and efficacy over a number of years, but data on radiation exposure of personnel have remained unavailable to date. The aim of this study was to assess the radiation exposure of the physician during intra-arterial 131I-Lipiodol therapy for liver malignancies and to develop appropriate radiation protection measures and equipment. During 20 intra-arterial administrations of 131I-Lipiodol (1110-1924 MBq), radiation dose equivalents (RDE) to the whole body, fingers and eyes of the physician were determined for (a) conventional manual administration through a shielded syringe, (b) administration with an automatic injector and (c) administration with a lead container developed in-house. Administration by syringe resulted in a finger RDE of 19.5 mSv, an eye RDE of 130-140 microSv, and a whole-body RDE of 108-119 microSv. The injector reduced the finger RDE to 5 mSv. With both technique (a) and technique (b), contamination of angiography materials was observed. The container allowed safe transport and administration of the radiopharmaceutical from 4 m distance and reduced the finger RDE to <3 microSv and the eye RDE to <1 microSv during injection. During femoral artery compression, radiation exposure to the fingers reached 170 microSv, but the whole-body dose could be reduced from a mean RDE of 114 microSv to 14 microSv. No more contamination occurred. In conclusion, radiation exposure was high when 131I-Lipiodol was administered by syringe or injector, but was significantly reduced with the lead container.

Superselective intra-arterial hepatic injection of indocyanine green (ICG) for fluorescence image-guided segmental positive staining: experimental proof of the concept.

PubMed

Diana, Michele; Liu, Yu-Yin; Pop, Raoul; Kong, Seong-Ho; Legnèr, Andras; Beaujeux, Remy; Pessaux, Patrick; Soler, Luc; Mutter, Didier; Dallemagne, Bernard; Marescaux, Jacques

2017-03-01

Intraoperative liver segmentation can be obtained by means of percutaneous intra-portal injection of a fluorophore and illumination with a near-infrared light source. However, the percutaneous approach is challenging in the minimally invasive setting. We aimed to evaluate the feasibility of fluorescence liver segmentation by superselective intra-hepatic arterial injection of indocyanine green (ICG). Eight pigs (mean weight: 26.01 ± 5.21 kg) were involved. Procedures were performed in a hybrid experimental operative suite equipped with the Artis Zeego ® , multiaxis robotic angiography system. A pneumoperitoneum was established and four laparoscopic ports were introduced. The celiac trunk was catheterized, and a microcatheter was advanced into different segmental hepatic artery branches. A near-infrared laparoscope (D-Light P, Karl Storz) was used to detect the fluorescent signal. To assess the correspondence between arterial-based fluorescence demarcation and liver volume, metallic markers were placed along the fluorescent border, followed by a 3D CT-scanning, after injecting intra-arterial radiological contrast (n = 3). To assess the correspondence between arterial and portal supplies, percutaneous intra-portal angiography and intra-arterial angiography were performed simultaneously (n = 1). Bright fluorescence signal enhancing the demarcation of target segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence between the volume of hepatic segments and arterial territories was confirmed by CT angiography. Higher background fluorescence noise was found after positive staining by intra-portal ICG injection, due to parenchymal accumulation and porto-systemic shunting. Intra-hepatic arterial ICG injection, rapidly highlights hepatic target segment borders, with a better signal-to-background ratio as compared to portal vein injection, in the experimental setting.

Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects.

PubMed

Savic, Lynn Jeanette; Chapiro, Julius; Geschwind, Jean-François H

2017-02-01

Intrahepatic cholangiocarcinoma (ICC) is a rare disease and carries a poor prognosis with surgery remaining the only curative treatment option. However, due to the late presentation of symptoms and close proximity of the tumors to central hepatic structures, only about 30% of patients are classified eligible to resection. As for palliative approaches, ICC constitutes a possible indication for loco-regional therapies (LRT). As such, intra-arterial therapies (IAT) are reported to be feasible, safe and effective in inducing tumor response in unresectable ICC. The paradigm of IAT is premised on the selective delivery of embolic, chemotherapeutic agents to the tumor via its feeding arteries, thus allowing dose escalation within the carcinoma and reduction of systemic toxicity. Conventional transcatheter arterial chemoembolization (cTACE) so far remains the most commonly used IAT modality. However, drug-eluting beads (DEB)-TACE was initiated with the idea of more selective targeting of the tumor owing to the combined embolizing as well as drug-eluting properties of the microspheres used in this setting. Moreover, radioembolization is performed by intra-arterial administration of very small spheres containing β-emitting yttrium-90 (Y90-RE) to the site of the tumor. Clinical evidence exists in support of survival benefits for IAT in the palliative treatment of ICC compared to surgery and systemic chemotherapy. As for combination regimens, cTACE, DEB-TACE and Y90-RE are reported to achieve conversion of patients to surgery in a sequential treatment planning and simultaneous IAT combinations may provide a therapeutic option for treatment escalation. Regarding the current status of literature, controlled randomized prospective trials to compare different IAT techniques and combination therapies as well as treatment recommendations for different IAT modalities are needed.

Renal Hemodynamics and Ammoniagenesis

PubMed Central

Lemieux, Guy; Vinay, Patrick; Cartier, Pierre

1974-01-01

Renal production of ammonia by the left kidney was studied in 31 acidotic dogs (NH4Cl) after acute constriction of the renal artery. Renal ammoniagenesis fell in direct proportion with the reduction in glomerular filtration rate and renal plasma flow. The renal extraction of glutamine by the experimental kidney fell in direct proportion with the reduction in renal hemodynamics. Extracted glutamine remained greater than filtered glutamine indicating that both the luminal and antiluminal transport sites were operative. The relationship between renal extraction of glutamine and ammoniagenesis observed during control was maintained after renal artery constriction (1.7 μmol NH3 produced for each μmol of glutamine extracted). Systemic venous or renal intra-arterial infusion of glutamine during arterial constriction increased renal production of ammonia to or above control values. These observations indicate that the mechanisms responsible for glutamine extraction and ammonia production were operating normally despite reduced hemodynamics. When measured immediately after arterial clamping, the renal venous pNH3 was found to rise significantly decreasing progressively thereafter towards control values. The extracted fraction of total glutamine delivered to the kidney (31%) did not change after acute reduction of the glutamine load. Thus, the antiluminal extraction site was incapable of lowering renal venous plasma glutamine concentration below 0.33 μM/ml. In a second series of experiments, the properties of the antiluminal site of transport for glutamine were studied after complete occlusion of the left ureter in acidotic and nonacidotic animals. Under these circumstances, it was demonstrated that the antiluminal site is capable of extracting sufficient glutamine to maintain total ammonia production at 60% or more of control. In acidotic animals, changes in cellular pNH3 appeared to play a key role on the antiluminal extraction of glutamine since the significant rise in renal blood flow often observed after ureteral occlusion prevented the rise in pNH3 noted when blood flow remained constant. Thus, when renal blood flow rose glutamine extraction and ammonia production were maintained at control values. In these acidotic animals, glutamine infusion failed to influence ammonia production until luminal transport was restored by release of ureteral clamp and resumption of glomerular filtration. The latter observation establishes that reabsorbed glutamine is utilized at least in part for ammonia production. PMID:4812445

Neural vasodilator control in the rectum of the cat and its possible mediation by vasoactive intestinal polypeptide.

PubMed Central

Andersson, P O; Bloom, S R; Edwards, A V; Järhult, J; Mellander, S

1983-01-01

Vascular and motor responses in the rectum to pelvic nerve stimulation are described in the anaesthetized cat and compared with corresponding effects observed in the colon. The responses comprise a cholinergic and a non-cholinergic component, and an attempt has been made to elucidate the latter. Pelvic nerve stimulation evoked a pronounced and well maintained vasodilator response in the rectum whereas that in the colon was transient. Maximal vasodilatation occurred at much lower stimulus frequencies in the rectum (2-4 Hz) than it did in the colon (8-16 Hz) and maximal blood flow under these conditions was also greater in the rectum (greater than 200 ml 100 g-1 min-1) than the colon (less than 150 ml 100 g-1 min-1). Muscarinic blockade further curtailed the colonic vasodilator response to pelvic nerve stimulation, whereas the rectal dilatation was only slightly reduced in the presence of atropine. Pelvic nerve stimulation caused a substantial release of vasoactive intestinal polypeptide (VIP) from the rectum, which was related both in magnitude and duration to the vasodilatation. Intra-arterial infusions of VIP, which reproduced this rise in rectal venous VIP concentration, caused a rectal vasodilator response which closely resembled that during pelvic nerve stimulation after cholinergic blockade. The rectal vasculature was estimated to be 50-100 times more sensitive to VIP than the colonic vasculature. VIP therefore seems to be the most likely putative neurotransmitter responsible for non-cholinergic rectal vasodilatation. Stimulation of the pelvic nerves also caused rapid contractile motor responses before, and more gradual motor responses after, muscarinic blockade in both the colon and rectum, in the latter preceded by a non-cholinergic relaxation. These patterns of motor activity largely confirm previous results. Infusions of substance P effectively mimicked the non-cholinergic contractile motor responses but failed to demonstrate significant release of this peptide during pelvic nerve stimulation in the present experiments. However, substance P is rapidly inactivated and might possibly be involved in these responses. Stimulation of the pelvic nerves in bursts at high frequencies (up to 80 Hz), simulating a discharge pattern observed electrophysiologically in vivo, was effective in eliciting all the above responses, with the exception of the colonic contraction. PMID:6197521

A Comparison of Approaches to Detect Deception

DTIC Science & Technology

2010-12-30

blood pressure has been demonstrated for this instrument (Fortin et al., 2006; Sackl- Pietsch , 2010). A sampling rate of 62.5 Hz is considerably...Psychophysiology, 15, 344-359. Sackl- Pietsch , E. (2010). Continuous non-invasive arterial pressure shows high accuracy in comparison to invasive intra-arterial

Multimodal assessment of spatial distribution of drug-tracer uptake by brain tissue after intra-arterial injections

NASA Astrophysics Data System (ADS)

Singh-Moon, Rajinder; Chaudhuri, Durba; Wang, Mei; Straubinger, Robert; Bigio, Irving J.; Joshi, Shailendra

2014-02-01

It is challenging to track the rapid changes in drug concentrations after intra-arterial (IA) administration to elucidate the pharmacokinetics of this method of drug delivery. Traditional pharmacokinetic parameters (such as protein binding) that are highly relevant to intravenous (IV) administration do not seem to apply to IA injections. Regional drug delivery is affected by the biomechanics of drug injection, resting blood flow, and local tissue extraction. In-vivo and ex-vivo, optical methods for spatial mapping of drug deposition can assist in visualizing drug distributions and aid in the screening of potential drugs and carrier candidates. We present a multimodal approach for the assessment of drug distribution in postmortem tissue specimens using diffuse reflectance spectroscopy, multispectral imaging, and confocal microscopy and demonstrate feasibility of distinguishing route of administration advantages of liposome-dye conjugate delivery. The results of this study suggest that insight on drug dynamics gained by this aggregated approach can be used to help screen and/or optimize potential drug candidates and drug delivery protocols.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

PubMed Central

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-01

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke. PMID:28091591

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia.

PubMed

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-16

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

NASA Astrophysics Data System (ADS)

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-01

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

Continuous intra-arterial blood-gas monitoring

NASA Astrophysics Data System (ADS)

Divers, George A.; Riccitelli, Samuel D.; Blais, Maurice; Hui, Henry K.

1993-05-01

Fiber optic technology and optical fluorescence have made the continuous monitoring of arterial blood gases a reality. Practical products that continuously monitor blood gases by use of an invasive sensor are now available. Anesthesiologists and intensive care physicians are beginning to explore the practical implications of this technology. With the advent of intra- arterial blood gas monitors it is possible to assess arterial blood gas values without the labor intensive steps of drawing blood and transporting a blood sample to the lab followed by the actual analysis. These intra-arterial blood gas monitors use new optical sensor technologies that can be reduced in size to the point that the sensor can be inserted into the arterial blood flow through a 20-gauge arterial cannula. In the best of these technologies the sensors accuracy and precision are similar to those in vitro analyzers. This presentation focuses on background technology and in vivo performance of a device developed, manufactured, and marketed by Puritan-Bennett Corporation.

The efficacy of nimodipine drug delivery using mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles.

PubMed

Huang, Shuling; Yu, Xiaohong; Yang, Linlin; Song, Fenglan; Chen, Gang; Lv, Zhufen; Li, Tiao; Chen, De; Zhu, Wanhua; Yu, Anan; Zhang, Yongming; Yang, Fan

2014-10-15

In order to develop and compare mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles, with the intention to develop a highly efficient formulation for nimodipine (NIM), NIM-loaded micelles and mixed micelles were made and their pharmacokinetics were studied. Single factor experiments and orthogonal experiments were designed to optimize the final preparation process, characterizations and drug release behaviors were studied. Pharmacokinetics of NIM micelles, NIM mixed micelles were researched and were compared to NIM solution. Micelles and mixed micelles were prepared by solvent evaporation method, with relatively high drug loading efficiency and within nano-particle size range. The CMC value of mPEG-PLA was lower than that of mPEG-PLA/TPGS. The results of FTIR and TEM confirmed the spherical core-shell structure of micelles as well as mixed micelles, and the encapsulation of NIM inside the cores. In vitro release showed that micelles and mixed micelles had sustained release effect in the forms of passive diffusion and dissolution process, respectively. Following intraperitoneal administration (5mg/kg), micelles and mixed micelles were absorbed faster than solution, and with larger MRT(0-t), smaller CLz and larger AUC(0-t) as compared to that of solution, which showed micelles and mixed micelles had higher retention, slower elimination and higher bioavailability. This experiment also showed that mixed micelles released NIM more stably than micelles. By evaluate the bioequivalence, NIM micelles and NIM mixed micelles were testified non-bioequivalent to NIM solution. Micelles and mixed micelles could sustain the NIM concentrations more efficiently in plasma as compared to solution. Mixed micelles were the best ones since they had high loading content and released more stably. Thus, apprehending micelles and mixed micelles were suited as poor aqueous solubility drug carriers, and mixed micelles were better due to their high loading content and more stable release. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective effects of notoginsenoside R1 on cerebral ischemia-reperfusion injury in rats.

PubMed

Zou, Shun; Zhang, Mingxiong; Feng, Limei; Zhou, Yuanfang; Li, Li; Ban, Lili

2017-12-01

The objective of this study was to investigate the protective effect of notoginsenoside R1 (NGR1) on cerebral ischemia-reperfusion injury (CIRI) in rats, and its molecular mechanism, to provide new insights into the diagnosis and treatment of CIRI. Sixty Sprague-Dawley rats were randomly divided into four groups including the sham-operation group (Sham), cerebral ischemia-reperfusion model group (CIR), NGR1 treatment group (NGR1), and nimodipine positive control group (NDC) with 15 rats each. Bilateral common carotid arteries occlusion was used to establish the rat CIRI model. The area of cerebral infarction at the end of reperfusion was calculated by triphenyl tetrazolium chloride staining. Apoptosis of hippocampal neurons in each group was detected by Annexin V/propidium iodide double staining. Hippocampal expression of brain-derived neurotrophic factor (BDNF) mRNA, and Bcl-2 and Bax protein at the end of reperfusion were measured by RT-qPCR and western blot analysis, respectively. Data were analyzed by SPSS software analysis to ensure statistical significance. At the end of reperfusion, the area of cerebral infarction in the NGR1 and NDC groups was significantly smaller than that of the CIR group. Apoptosis analysis showed that compared with the CIR group, the apoptosis rate of hippocampal neurons was significantly decreased in the NGR1 and NDC groups. RT-qPCR and western blot analysis showed that at the end of reperfusion, higher levels of BDNF mRNA and the anti-apoptotic factor, Bcl-2, and lower levels of the pro-apoptotic factor, Bax, in the hippocampus were found in the NGR1 and NDC groups compared with the CIR group. The protective effect of NGR1 on CIRI was significantly stronger than that of nimodipine. In conclusion, NGR1 can reduce the area of cerebral infarction, reduce apoptosis of hippocampal neurons, and protect rats from CIRI. Those effects were achieved by activating the expression of BDNF and Bcl-2, and by inhibiting the expression of Bax.

Receptor model for the molecular basis of tissue selectivity of 1,4-dihydropyridine calcium channel drugs

NASA Astrophysics Data System (ADS)

Langs, David A.; Strong, Phyllis D.; Triggle, David J.

1990-09-01

Our analysis of the solid state conformations of nifedipine [dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylate] and its 1,4-dihydropyridine (1,4-DHP) analogues produced a cartoon description of the important interactions between these drugs and their voltage-dependent calcium channel receptor. In the present study a molecular-level detailed model of the 1,4-DHP receptor binding site has been built from the published amino acid sequence of the 215-1 subunit of the voltage-dependent calcium channel isolated from rabbit skeletal muscle transverse tubule membranes. The voltage-sensing component of the channel described in this work differs from others reported for the homologous sodium channel in that it incorporates a water structure and a staggered, rather than eclipsed, hydrogen bonded S4 helix conformation. The major recognition surfaces of the receptor lie in helical grooves on the S4 or voltagesensing α-helix that is positioned in the center of the bundle of transmembrane helices that define each of the four calcium channel domains. Multiple binding clefts defined by Arg-X-X-Arg-P-X-X-S `reading frames' exist on the S4 strand. The tissue selectivity of nifedipine and its analogues may arise, in part, from conservative changes in the amino acid residues at the P and S positions of the reading frame that define the ester-binding regions of receptors from different tissues. The crystal structures of two tissue-selective nifedipine analogues, nimodipine [isopropyl (2-methoxyethyl) 1,4-dihydro-2,6- dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] and nitrendipine [ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinecarboxylate] are reported. Nimodipine was observed to have an unusual ester side chain conformation that enhances the fit to the proposed ester-sensing region of the receptor.

Beneficial Effects of Apelin on Vascular Function in Patients With Central Obesity.

PubMed

Schinzari, Francesca; Veneziani, Augusto; Mores, Nadia; Barini, Angela; Di Daniele, Nicola; Cardillo, Carmine; Tesauro, Manfredi

2017-05-01

Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT 1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr 1 )apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients. In the absence of hyperinsulinemia, forearm blood flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during saline or apelin administration (both P >0.05). During intra-arterial infusion of regular insulin, however, apelin enhanced the vasodilation induced by both acetylcholine and nitroprusside (both P <0.05). Interestingly, the vasodilator effect of concurrent blockade of AT 1 (telmisartan) and AT 2 (PD 123,319) receptors was blunted by apelin (3±5% versus 32±9%; P <0.05). Similarly, during apelin administration, blockade of ET A receptors (BQ-123) resulted in lower vasodilator response than during saline (23±10% versus 65±12%; P <0.05). NO synthase inhibition by L-NMMA (l- N -monometylarginine) during the concurrent blockade of either Ang II or ET A receptors resulted in similar vasoconstriction in the absence or presence of apelin ( P >0.05). In conclusion, in patients with central obesity, apelin has favorable effects not only to improve insulin-stimulated endothelium-dependent and endothelium-independent vasodilator responses but also to blunt Ang II- and ET-1-dependent vasoconstriction by a mechanism not involving NO. Taken together, our results suggest that targeting the apelin system might favorably impact some hemodynamic abnormalities of insulin-resistant states like obesity. © 2017 American Heart Association, Inc.

Novel Software-Assisted Hemodynamic Evaluation of Pelvic Flow During Chemoperfusion of Pelvic Arteries for Bladder Cancer: Double- Versus Single-Balloon Technique

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

Yamamoto, Kiyohito, E-mail: rad105@poh.osaka-med.ac.jp; Yamamoto, Kazuhiro, E-mail: rad043@poh.osaka-med.ac.jp; Nakai, Go, E-mail: rad091@poh.osaka-med.ac.jp

2016-06-15

PurposeApproximately 83 % of patients with bladder cancer have achieved a complete response after undergoing a novel bladder preservation therapy involving balloon-occluded intra-arterial infusion chemotherapy (BOAI) using a four-lumen double-balloon catheter, known as the Osaka Medical College regimen. This study aimed to show the quantitative difference in hemodynamics of the bladder arteries using syngo iFlow (Siemens Healthcare, Erlangen, Germany), which provides an automatic tool for quantitative blood flow analysis between double BOAI (D-BOAI) and conventional single BOAI (S-BOAI).Materials and MethodsFifty patients were included. The catheters were introduced into both posterior trunks of the internal iliac arteries via contralateral femoral artery access.more » A side hole between the distal and proximal balloons was placed at the origin of each bladder artery to allow clear visualization of angiographic flow of the injected agent into the urinary bladder. Digital subtraction angiography was used during analysis with the syngo iFlow to evaluate the hemodynamics of the contrast medium in the pelvic arteries during BOAI. The comparative change in the amount of contrast medium in the bladder arteries between D-BOAI and S-BOAI was assessed using syngo iFlow.ResultsOne-hundred pelvic sides were analyzed. The amount of contrast medium in the bladder arteries using D-BOAI was more than twice that using S-BOAI (right, 3.03-fold; left, 2.81-fold).ConclusionThe amount of contrast medium in the bladder arteries using D-BOAI was higher than that using conventional S-BOAI. This may increase the anticancer drug concentration in the affected bladder, leading to a good clinical response.« less

Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men.

PubMed

Lucking, Andrew J; Lundbäck, Magnus; Barath, Stefan L; Mills, Nicholas L; Sidhu, Manjit K; Langrish, Jeremy P; Boon, Nicholas A; Pourazar, Jamshid; Badimon, Juan J; Gerlofs-Nijland, Miriam E; Cassee, Flemming R; Boman, Christoffer; Donaldson, Kenneth; Sandstrom, Thomas; Newby, David E; Blomberg, Anders

2011-04-26

In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men. Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 μg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release. Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.

Uric acid and endothelial function in elderly community-dwelling subjects.

PubMed

Ticinesi, Andrea; Lauretani, Fulvio; Ceda, Gian Paolo; Ruggiero, Carmelinda; Ferrucci, Luigi; Aloe, Rosalia; Larsson, Anders; Cederholm, Tommy; Lind, Lars; Meschi, Tiziana; Maggio, Marcello

2017-03-01

The role of serum uric acid (SUA), an inflammatory agent and potential mediator of cardiovascular diseases, in endothelial function (EF) has been tested only in middle-aged subjects affected by specific diseases. Our aim was to assess the relationship between SUA and measures of EF in a cohort of elderly community-dwellers. This study involved 424 males and 426 females aged 70years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), having complete data on SUA and EF assessed by flow-mediated vasodilation (FMD) and by intra-arterial infusion of acetylcholine (endothelium-dependent vasodilation, EDV) and sodium nitroprusside (endothelium-independent vasodilation, EIDV). Univariate and multivariate regression models obtained by backward selection from initial fully-adjusted models were built to assess the relationship between SUA and measures of EF in both genders. Cardiovascular risk factors, serum hormonal and metabolic mediators, and body composition were considered as potential confounders. In the univariate model, SUA was inversely associated in both genders with log(EDV) (β±SE males -0.39±0.17, p=0.03; females -0.57±0.19, p=0.003) and log(EIDV) (males -0.23±0.12, p=0.05; females -0.49±0.15, p=0.002), but not with log(FMD). After adjustment for BMI, only the association between SUA and log(EIDV) in females persisted, though attenuated (-0.32±0.16, p=0.049), and was no longer significant in the fully-adjusted multivariate model including waist/hip ratio. In conclusion, in older subjects, especially women, SUA is associated with EF not independently of a list of confounders including BMI and trunk fat mass, suggesting a role as surrogate metabolic marker rather than an active player in EF. Copyright © 2017 Elsevier Inc. All rights reserved.

Uric acid and endothelial function in elderly community-dwelling subjects

PubMed Central

Ticinesi, Andrea; Lauretani, Fulvio; Ceda, Gian Paolo; Ruggiero, Carmelinda; Ferrucci, Luigi; Aloe, Rosalia; Larsson, Anders; Cederholm, Tommy; Lind, Lars; Meschi, Tiziana; Maggio, Marcello

2017-01-01

The role of serum uric acid (SUA), an inflammatory agent and potential mediator of cardiovascular diseases, in endothelial function (EF) has been tested only in middle-aged subjects affected by specific diseases. Our aim was to assess the relationship between SUA and measures of EF in a cohort of elderly community-dwellers. This study involved 424 males and 426 females aged 70 years from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), having complete data on SUA and EF assessed by flow-mediated vasodilation (FMD) and by intra-arterial infusion of acetylcholine (endothelium-dependent vasodilation, EDV) and sodium nitroprusside (endothelium-independent vasodilation, EIDV). Univariate and multivariate regression models obtained by backward selection from initial fully-adjusted models were built to assess the relationship between SUA and measures of EF in both genders. Cardiovascular risk factors, serum hormonal and metabolic mediators, and body composition were considered as potential confounders. In the univariate model, SUA was inversely associated in both genders with log(EDV) (β ± SE males −0.39 ± 0.17, p = 0.03; females −0.57 ± 0.19, p = 0.003) and log(EIDV) (males −0.23 ± 0.12, p = 0.05; females −0.49 ± 0.15, p = 0.002), but not with log(FMD). After adjustment for BMI, only the association between SUA and log(EIDV) in females persisted, though attenuated (−0.32 ± 0.16, p = 0.049), and was no longer significant in the fully-adjusted multivariate model including waist/hip ratio. In conclusion, in older subjects, especially women, SUA is associated with EF not independently of a list of confounders including BMI and trunk fat mass, suggesting a role as surrogate metabolic marker rather than an active player in EF. PMID:28057563

Continuous positive airway pressure improves vascular function in obstructive sleep apnoea/hypopnoea syndrome: a randomised controlled trial.

PubMed

Cross, M D; Mills, N L; Al-Abri, M; Riha, R; Vennelle, M; Mackay, T W; Newby, D E; Douglas, N J

2008-07-01

The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.

Involvement of substance P present in primary afferent neurones in modulation of cutaneous blood flow in the instep of rat hind paw.

PubMed Central

Yonehara, N.; Chen, J. Q.; Imai, Y.; Inoki, R.

1992-01-01

1. The participation of small-diameter afferent fibres in the microcirculatory haemodynamics of cutaneous tissue was examined by studies on the effects of antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF) and tachykinin release into the subcutaneous space in the instep of the hind paw of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a biphasic flow response, an initial transient decrease followed by an increase, with no alteration in the blood pressure. 3. Neither phase was affected by pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1, i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4. Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal CBF, and also inhibited both phases of the biphasic flow response evoked by antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic stimulation of the sectioned sciatic nerve caused a marked increase in SP release into the subcutaneous perfusate of the instep of the rat hind paw, but no detectable increase in neurokinin A release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382777

Nitric oxide and passive limb movement: a new approach to assess vascular function

PubMed Central

Trinity, Joel D; Groot, H Jonathan; Layec, Gwenael; Rossman, Matthew J; Ives, Stephen J; Runnels, Sean; Gmelch, Ben; Bledsoe, Amber; Richardson, Russell S

2012-01-01

Passive limb movement elicits a robust increase in limb blood flow (LBF) and limb vascular conductance (LVC), but the peripheral vascular mechanisms associated with this increase in LBF and LVC are unknown. This study sought to determine the contribution of nitric oxide (NO) to movement-induced LBF and LVC and document the potential for passive-limb movement to assess NO-mediated vasodilatation and therefore NO bioavailability. Six subjects underwent passive knee extension with and without nitric oxide synthase (NOS) inhibition via intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central haemodynamics were measured by finger photoplethysmography. Although l-NMMA did not alter the immediate increase (initial ∼9 s) in LBF and LVC, NOS blockade attenuated the peak increase in LBF (control: 653 ± 81; l-NMMA: 399 ± 112 ml−1 min−1, P= 0.03) and LVC (control: 7.5 ± 0.8; l-NMMA: 4.1 ± 1.1 ml min−1 mmHg−1, P= 0.02) and dramatically reduced the overall vasodilatory and hyperaemic response (area under the curve) by nearly 80% (LBF: control: 270 ± 51; l-NMMA: 75 ± 32 ml, P= 0.001; LVC: control: 2.9 ± 0.5; l-NMMA: 0.8 ± 0.3 ml mmHg−1, P < 0.001). Passive movement in control and l-NMMA trials evoked similar increases in heart rate, stroke volume, cardiac output and a reduction in mean arterial pressure. As movement-induced increases in LBF and LVC are predominantly NO dependent, passive limb movement appears to have significant promise as a new approach to assess NO-mediated vascular function, an important predictor of cardiovascular disease risk. PMID:22310310

Colonic motor and vascular responses to pelvic nerve stimulation and their relation to local peptide release in the cat.

PubMed Central

Andersson, P O; Bloom, S R; Järhult, J

1983-01-01

1. The effects of stimulation of the pelvic nerves in atropinized cats at continuous, low frequencies from 1 to 16 Hz (continuous stimulation) were compared with those of stimulation at higher frequencies (10-160 Hz) delivered in 1 s bursts at 10 s intervals (stimulation in bursts), the latter simulating a commonly observed discharge pattern in vivo. Both types of stimulation evoked a transient vasodilatation. Stimulation in bursts at 20 and 40 Hz evoked more pronounced vasodilatations than continuous stimulation delivering exactly the same number of impulses over the whole period of excitation. 2. Stimulation of the pelvic nerves in bursts failed to elicit an effective contraction of the colon at any frequency tested, whereas continuous stimulation invariably evoked a contraction. 3. There was a clear-cut increase in the output of vasoactive intestinal polypeptide during both continuous and intermittent stimulation of the pelvic nerves. Stimulation in bursts caused a small but significant increase in the output of somatostatin but there was no change in the output of substance P in response to either type of pelvic nerve stimulation. 4. The colonic muscular contraction in response to continuous stimulation of the pelvic nerves was not affected by somatostatin when infused intra-arterially at the large dose of 1.0 microgram/min. 5. It is concluded that the colonic responses of atropinized cats to pelvic nerve stimulation can be substantially altered merely by changing the pattern of stimulation. Thus, whereas continuous stimulation produces both muscular contraction and vasodilatation, stimulation in bursts favours vasodilatation but is ineffective in eliciting colonic contraction. PMID:6191025

Effects of peptides derived from dietary proteins on mucus secretion in rat jejunum.

PubMed

Claustre, Jean; Toumi, Férial; Trompette, Aurélien; Jourdan, Gérard; Guignard, Henri; Chayvialle, Jean Alain; Plaisancié, Pascale

2002-09-01

The hypothesis that dietary proteins or their hydrolysates may regulate intestinal mucin discharge was investigated in the isolated vascularly perfused rat jejunum using an enzyme-linked immunosorbent assay for rat intestinal mucins. On luminal administration, casein hydrolysate [0.05-5% (wt/vol)] stimulated mucin secretion in rat jejunum (maximal response at 417% of controls). Lactalbumin hydrolysate (5%) also evoked mucin discharge. In contrast, casein, and a mixture of amino acids was without effect. Chicken egg albumin and its hydrolysate or meat hydrolysate also did not modify mucin release. Interestingly, casein hydrolysate-induced mucin secretion was abolished by intra-arterial TTX or naloxone (an opioid antagonist). beta-Casomorphin-7, an opioid peptide released from beta-casein on milk ingestion, induced a strong mucin secretion (response at 563% of controls) that was inhibited by naloxone. Intra-arterial beta-casomorphin-7 also markedly increased mucin secretion (410% of controls). In conclusion, two enzymatic milk protein hydrolysates (casein and lactalbumin hydrolysates) and beta-casomorphin-7, specifically, induced mucin release in rat jejunum. The casein hydrolysate-induced mucin secretion is triggered by a neural pathway and mediated by opioid receptor activation.

A Comparison and Calibration of a Wrist-Worn Blood Pressure Monitor for Patient Management: Assessing the Reliability of Innovative Blood Pressure Devices

PubMed Central

Melville, Sarah; Teskey, Robert; Philip, Shona; Simpson, Jeremy A; Lutchmedial, Sohrab

2018-01-01

Background Clinical guidelines recommend monitoring of blood pressure at home using an automatic blood pressure device for the management of hypertension. Devices are not often calibrated against direct blood pressure measures, leaving health care providers and patients with less reliable information than is possible with current technology. Rigorous assessments of medical devices are necessary for establishing clinical utility. Objective The purpose of our study was 2-fold: (1) to assess the validity and perform iterative calibration of indirect blood pressure measurements by a noninvasive wrist cuff blood pressure device in direct comparison with simultaneously recorded peripheral and central intra-arterial blood pressure measurements and (2) to assess the validity of the measurements thereafter of the noninvasive wrist cuff blood pressure device in comparison with measurements by a noninvasive upper arm blood pressure device to the Canadian hypertension guidelines. Methods The cloud-based blood pressure algorithms for an oscillometric wrist cuff device were iteratively calibrated to direct pressure measures in 20 consented patient participants. We then assessed measurement validity of the device, using Bland-Altman analysis during routine cardiovascular catheterization. Results The precalibrated absolute mean difference between direct intra-arterial to wrist cuff pressure measurements were 10.8 (SD 9.7) for systolic and 16.1 (SD 6.3) for diastolic. The postcalibrated absolute mean difference was 7.2 (SD 5.1) for systolic and 4.3 (SD 3.3) for diastolic pressures. This is an improvement in accuracy of 33% systolic and 73% diastolic with a 48% reduction in the variability for both measures. Furthermore, the wrist cuff device demonstrated similar sensitivity in measuring high blood pressure compared with the direct intra-arterial method. The device, when calibrated to direct aortic pressures, demonstrated the potential to reduce a treatment gap in high blood pressure measurements. Conclusions The systolic pressure measurements of the wrist cuff have been iteratively calibrated using gold standard central (ascending aortic) pressure. This improves the accuracy of the indirect measures and potentially reduces the treatment gap. Devices that undergo auscultatory (indirect) calibration for licensing can be greatly improved by additional iterative calibration via intra-arterial (direct) measures of blood pressure. Further clinical trials with repeated use of the device over time are needed to assess the reliability of the device in accordance with current and evolving guidelines for informed decision making in the management of hypertension. Trial Registration ClinicalTrials.gov NCT03015363; https://clinicaltrials.gov/ct2/show/NCT03015363 (Archived by WebCite at http://www.webcitation.org/6xPZgseYS) PMID:29695375

[Effect of the proteolytic enzyme papain on the body organs and systems of experimental animals].

PubMed

Udod, V M; Storozhuk, V T; Trofimenko, S P; Shabash, E G; Markelov, S I

1983-01-01

When administered intravenously and intraarterially papaine (2.5 and 10 mg/kg) produces no toxic effects on respiration, arterial pressure, brain and intracranial circulation. Intrapleural, intraperitoneal and interstitial administration of papaine solutions in doses under 4.5 mg/kg produces no local or general changes on the part of experimental animals' organism.

[Application of continuous intra-arterial blood gas monitoring system "Paratrend 7" for pulmonary lavage of a patient with alveolar proteinosis].

PubMed

Harigae, M; Hirose, Y; Gamo, M; Hirose, M; Fujiwara, C; Matsuo, K

1999-03-01

We applied a continuous intra-arterial blood gas monitoring system (Paratrend 7) to a patient with pulmonary alveolar proteinosis during pulmonary lavage. Lavage was performed under general anesthesia with one lung ventilation. We inserted the sensor of Patatrend 7 through a 20 G catheter into the radial artery, and monitored pH, PaCO2 and PaO2 continuously throughout the procedure. SpO2 and EtCO2 were also monitored. Saline 1000-1500 ml was instilled and drained repeatedly by volume limited methods. PaO2 values by Paratrend 7 increased during instillation and decreased during drainage of the irrigating fluid. In contrast, PaCO2 value by Paratrend 7 decreased slightly during instillation and increased during drainage. The change of SpO2 was almost the same as that by Paratrend 7, but the response time of pulse oxymetry was a little quicker than Paratrend 7. During the lavage procedure, respiratory and circulatory condition changed very rapidly, and it is necessary to monitor blood gas change intensively. Paratrend 7 is useful as a perioperative monitoring system, but pulse oxymetry might be sufficient during pulmonary lavage considering its cost.

Liver metastases from melanoma: hepatic intra-arterial chemotherapy. A retrospective study.

PubMed

Farolfi, A; Ridolfi, L; Guidoboni, M; Milandri, C; Calzolari, F; Scarpi, E; Amadori, D; Ridolfi, R

2011-10-01

The liver is the primary site of metastases in most uveal melanoma patients. We retrospectively investigated intraarterial chemotherapy (IAC) as treatment for patients with hepatic melanoma metastases.Twenty-three patients (18 with uveal melanoma) received fotemustine (14 patients, 61.9%) or carboplatin (9 patients, 31.1%) via hepatic IAC delivery. The catheter was introduced through percutaneous access to the femoral artery with drugs delivered directly to the hepatic artery, and was removed at the end of each treatment cycle. A total of 3 cycles was planned, repeated every 21 days. However, patients with a clinical response could receive more than 3 cycles, provided that the toxic effects were acceptable.IAC was well tolerated and no catheter-related complications or grade 4 toxicities were reported. Considering only uveal melanoma patients, the overall response rate and disease control rate was 16.7% and 38.9%, respectively. Median time to progression was 6.2 months (95% CI 3.7-10.5) and median overall survival was 21 months (95% CI 8-39).IAC is well tolerated and is a valid choice for patients with a poor prognosis since median survival rates are among the longest reported.

Multislice CT Angiography in Renal Artery Stent Evaluation: Prospective Comparison with Intra-Arterial Digital Subtraction Angiography

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

Raza, Syed A.; Chughtai, Aamer R.; Wahba, Mona

2004-01-15

Purpose: To assess the role of multislice computed tomography angiography (MCTA) in the evaluation of renal artery stents, using intra-arterial digital subtraction angiography (DSA) as the gold standard. Methods: Twenty consecutive patients (15 men, 5 women) with 23 renal artery stents prospectively underwent both MCTA and DSA. Axial images, multiplanar reconstructions and maximum intensity projection images were used for diagnosis. The MCTA and DSA images were each interpreted without reference to the result of the other investigation. Results:The three cases of restenosis on DSA were detected correctly by MCTA; in 19 cases where MCTA showed a fully patent stent, themore » DSA was also negative. Sensitivity and negative predictive value (NPV) of MCTA were therefore 100%. In four cases, MCTA showed apparently minimal disease which was not shown on DSA. These cases are taken as false positive giving a specificity of 80% and a positive predictive value of 43%. Conclusion: The high sensitivity and NPV suggest MCTA may be useful as a noninvasive screen for renal artery stentrestenosis. MCTA detected mild disease in a few patients which was not confirmed on angiography.« less

Recanalization Therapies in Acute Ischemic Stroke: Pharmacological Agents, Devices, and Combinations

PubMed Central

Sharma, Vijay K.; Teoh, Hock Luen; Wong, Lily Y. H.; Su, Jie; Ong, Benjamin K. C.; Chan, Bernard P. L.

2010-01-01

The primary aim of thrombolysis in acute ischemic stroke is recanalization of an occluded intracranial artery. Recanalization is an important predictor of stroke outcome as timely restoration of regional cerebral perfusion helps salvage threatened ischemic tissue. At present, intravenously administered tissue plasminogen activator (IV-TPA) remains the only FDA-approved therapeutic agent for the treatment of ischemic stroke within 3 hours of symptom onset. Recent studies have demonstrated safety as well as efficacy of IV-TPA even in an extended therapeutic window. However, the short therapeutic window, low rates of recanalization, and only modest benefits with IV-TPA have prompted a quest for alternative approaches to restore blood flow in an occluded artery in acute ischemic stroke. Although intra-arterial delivery of the thrombolytic agent seems effective, various logistic constraints limit its routine use and as yet no lytic agent have not received full regulatory approval for intra-arterial therapy. Mechanical devices and approaches can achieve higher rates of recanalization but their safety and efficacy still need to be established in larger clinical trials. The field of acute revascularization is rapidly evolving, and various combinations of pharmacologic agents, mechanical devices, and novel microbubble/ultrasound technologies are being tested in multiple clinical trials. PMID:20798838

[Selective embolization to treat obstetric hemorrhage].

PubMed

Ferrer Puchol, M D; Lanciego, C; Esteban, E; Ciampi, J J; Edo, M A; Ferragud, S

2014-01-01

To describe cases of obstetric hemorrhage that have called for selective intra-arterial embolization and the different embolization techniques used. To assess the clinical outcomes and postprocedural fertility. We studied 27 women with obstetric hemorrhage. In 24 patients, embolization was performed by catheterizing both uterine arteries and in 2 patients only one uterine artery was catheterized (pseudoaneurysm). The materials used for embolization consisted of Spongostan in 17/27, particles in 9/27, and coils in 1/27. Clinical follow-up included an analysis of early and late complications and of postprocedural fertility. Hemorrhage was classified as primary (25/27) or secondary (2/27). The cause of bleeding was vaginal delivery (20), cesarean sections (5), abortion (1), and cervical ectopic pregnancy (1). The initial technical success rate was 100% and the clinical success rate was 92.6% (25 of the 27 patients). Bleeding ceased and the outcome was satisfactory in 25 patients. During clinical follow-up ranging from one to seven years, 23 patients had normal menstruation and 6 patients completed 7 full-term pregnancies. Intra-arterial embolization for obstetric hemorrhage leads to good outcomes and few complications and it preserves fertility. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

Maintaining Supersaturation of Nimodipine by PVP with or without the Presence of Sodium Lauryl Sulfate and Sodium Taurocholate.

PubMed

Pui, Yipshu; Chen, Yuejie; Chen, Huijun; Wang, Shan; Liu, Chengyu; Tonnis, Wouter; Chen, Linc; Serno, Peter; Bracht, Stefan; Qian, Feng

2018-05-30

Amorphous solid dispersion (ASD) is one of the most versatile supersaturating drug delivery systems to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs. PVP based ASD formulation of nimodipine (NMD) has been marketed and effectively used in clinic for nearly 30 years, yet the mechanism by which PVP maintains the supersaturation and subsequently improves the bioavailability of NMD was rarely investigated. In this research, we first studied the molecular interactions between NMD and PVP by solution NMR, using CDCl 3 as the solvent, and the drug-polymer Flory-Huggins interaction parameter. No strong specific interaction between PVP and NMD was detected in the nonaqueous state. However, we observed that aqueous supersaturation of NMD could be significantly maintained by PVP, presumably due to the hydrophobic interactions between the hydrophobic moieties of PVP and NMD in aqueous medium. This hypothesis was supported by dynamic light scattering (DLS) and supersaturation experiments in the presence of different surfactants. DLS revealed the formation of NMD/PVP aggregates when NMD was supersaturated, suggesting the formation of hydrophobic interactions between the drug and polymer. The addition of surfactants, sodium lauryl sulfate (SLS) or sodium taurocholate (NaTC), into PVP maintained that NMD supersaturation demonstrated different effects: SLS could only improve NMD supersaturation with concentration above its critical aggregation concentration (CAC) value while not with lower concentration. Nevertheless, NaTC could prolong NMD supersaturation independent of concentration, with lower concentration outperformed higher concentration. We attribute these observations to PVP-surfactant interactions and the formation of PVP/surfactant complexes. In summary, despite the lack of specific interactions in the nonaqueous state, NMD aqueous supersaturation in the presence of PVP was attained by hydrophobic interactions between the hydrophobic moieties of NMD and PVP. This hydrophobic interaction could be disrupted by surfactants, which interact with PVP competitively, thus hindering the capability of PVP to maintain NMD supersaturation. Therefore, caution is needed when evaluating such ASDs in vitro and in vivo when various surfactants are present either in the formulation or in the surrounding medium.

Behavioural memory reconsolidation of food and fear memories

PubMed Central

Flavell, Charlotte R.; Barber, David J.; Lee, Jonathan L. C.

2012-01-01

The reactivation of a memory through retrieval can render it subject to disruption or modification through the process of memory reconsolidation. In both humans and rodents, briefly reactivating a fear memory results in effective erasure by subsequent extinction training. Here we show that a similar strategy is equally effective in the disruption of appetitive pavlovian cue–food memories. However, systemic administration of the NMDA receptor partial agonist D-cycloserine under the same behavioural conditions did not potentiate appetitive memory extinction, suggesting that reactivation does not enhance subsequent extinction learning. To confirm that reactivation followed by extinction reflects a behavioural analog of memory reconsolidation, we show that prevention of contextual fear memory reactivation by the LVGCC blocker nimodipine interferes with the amnestic outcome. Therefore, the reconsolidation process can be manipulated behaviourally to disrupt both aversive and appetitive memories. PMID:22009036

Application of molecular dynamics simulation to predict the compatability between water-insoluble drugs and self-associating poly(ethylene oxide)-b-poly(epsilon-caprolactone) block copolymers.

PubMed

Patel, Sarthak; Lavasanifar, Afsaneh; Choi, Phillip

2008-11-01

In the present work, molecular dynamics (MD) simulation was applied to study the solubility of two water-insoluble drugs, fenofibrate and nimodipine, in a series of micelle-forming PEO-b-PCL block copolymers with combinations of blocks having different molecular weights. The solubility predictions based on the MD results were then compared with those obtained from solubility experiments and by the commonly used group contribution method (GCM). The results showed that Flory-Huggins interaction parameters computed by the MD simulations are consistent with the solubility data of the drug/PEO-b-PCL systems, whereas those calculated by the GCM significantly deviate from the experimental observation. We have also accounted for the possibility of drug solubilization in the PEO block of PEO-b-PCL.

Reversible cerebral vasoconstriction syndrome with involvement of external carotid artery branches.

PubMed

Shaik, S; Chhetri, S K; Roberts, G; Wuppalapati, S; Emsley, H C A

2014-07-01

A 44-year-old woman presented with recurrent episodes of thunderclap headache. Neurological examination and computed tomography brain imaging were unremarkable. Cerebrospinal fluid findings were consistent with subarachnoid hemorrhage. Computed tomography angiography of the circle of Willis showed multiple areas of segmental vasoconstriction. This finding was confirmed on cerebral catheter angiography, with segmental vasoconstriction involving bilateral internal carotid, posterior cerebral, and external carotid branches. No aneurysm or other vascular abnormality was identified. She received treatment with nimodipine. A selective serotonin reuptake inhibitor, started 4 weeks earlier, was discontinued. Follow-up angiography after 3 months demonstrated complete resolution of the segmental vasoconstriction, confirming the diagnosis of reversible cerebral vasoconstriction syndrome (RCVS). She remained headache free at follow-up. To our knowledge, external carotid artery branch involvement in RCVS has been described only in one previous occasion.

Regional lipiodolized chemotherapy for cholangiocarcinoma associated with oral contraceptives.

PubMed Central

McAleer, J. J.; Dickey, W.; Clarke, R.; Johnston, G. W.; Callender, M. E.

1987-01-01

We describe a case of cholangiocarcinoma in a young woman, who presented with cholestatic jaundice following oral contraceptive ingestion. Following diagnostic laparotomy she received intra-arterial 'lipiodolized' chemotherapy. Intravenous mitozantrone was given for 2 years and she is asymptomatic, with computed tomographic evidence of tumour response, 27 months after diagnosis. We suggest that this form of treatment is of value for cholangiocarcinoma. PMID:2821526

First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment.

PubMed

Munier, Francis L; Mosimann, Pascal; Puccinelli, Francesco; Gaillard, Marie-Claire; Stathopoulos, Christina; Houghton, Susan; Bergin, Ciara; Beck-Popovic, Maja

2017-08-01

The introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes of consecutive patients with advanced unilateral disease treated with either first-line intravenous chemotherapy (IVC) or first-line IAC. This is a retrospective mono-centric comparative review of consecutive patients. Sporadic unilateral retinoblastoma group D cases treated conservatively at Jules-Gonin Eye Hospital and CHUV between 1997 and 2014. From January 1997 to August 2008, IVC, combined with focal treatments, was the primary treatment approach. From September 2008 to October 2014, IAC replaced IVC as first-line therapy. 48 patients met the inclusion criteria, receiving only either IAC or IVC as primary treatment modality. Outcomes of 23 patients treated by IVC were compared with those of 25 treated by IAC; mean follow-up was 105.3 months (range 29.2-218.6) and 41.7 months (range 19.6-89.5), respectively. Treatment duration was significantly shorter in the IAC group (p<0.001). Ten eyes in the IVC group underwent enucleation. Recordable visual acuity of the salvaged eyes was significantly better in the IAC group (0.9 vs 1.4 logarithm of the minimum angle of resolution, p<0.01). No extraocular disease, metastases or long-term systemic complications were observed in either group. The difference in the time frame between treatment groups had an impact on the availability of intravitreal chemotherapy treatment. Despite this, the results reported here imply that eyes treated with first-line IAC will have shorter treatment period, better ocular survival and visual acuity than first-line IVC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Experimental Evaluation of Early and Long-Term Effects of Microparticle Embolization in Two Different Mini-Pig Models. Part I: Kidney

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

Stampfl, S.; Stampfl, U.; Rehnitz, C.

Purpose. Using a pig model: (1) to evaluate the vascular distribution pattern, including the homogeneity and completeness of the intra-arterial microsphere distribution, of 40-120-{mu}m trisacryl-gelatin microspheres (Embospheres) in acute whole-kidney embolization; (2) to evaluate the durability and biocompatibility of 40-120-{mu}m trisacryl-gelatin microspheres (Embospheres) in chronic partial kidney embolization. Methods. Twenty-two animals were divided into four groups: group 1 (n = 4) underwent total arterial renal occlusion with immediate euthanasia. Groups 2-4 had chronic superselective and partial renal embolization with increasing follow-up times: group 2 (n = 2), 1 week; group 3 (n = 7), 4 weeks; and group 4 (nmore » = 9), 14 weeks. Key endpoints in group 1 were homogeneity and completeness of acute embolizations. In groups 2-4 the key endpoints were durability of embolization and particle-related inflammation in chronic partial embolizations as assessed by quantitative angiography or histomorphometry. A numerical angiographic occlusion score (0.0 to 4.0, where 3.0 is optimal) was developed to assess and quantify the angiographic durability of superselective embolizations (groups 2-4). Results. In group 1, a relatively homogeneous distribution of the particles from segmental arteries to the precapillary level was shown by histomorphometry. Some particles reached the glomerular vas afferens (10 {mu}m diameter). In groups 2-4, a mild recanalization appeared during follow-up. The immediate average postembolization occlusion score of 3.18 {+-} 0.73 was reduced to 1.44 {+-} 0.73 (statistically significant). Microscopy revealed subtotal necrosis but no foreign body granuloma formation. The intra-arterial appearance of giant cells closely attaching to the surface of the embolic spheres inside the vessel lumen was noted. Vessel walls showed major ischemic reactions. Conclusion. Microspheres 40-120 {mu}m in diameter might achieve total occlusion of the arterial kidney vasculature when injected centrally as a result of their fairly homogeneous distribution. Segmental renal infarction occurs after chronic partial embolization despite recanalizations during follow-up. Only mild specific intra-arterial foreign body reactions were found.« less

Appropriate use of CT perfusion following aneurysmal subarachnoid hemorrhage: a Bayesian analysis approach.

PubMed

Killeen, R P; Gupta, A; Delaney, H; Johnson, C E; Tsiouris, A J; Comunale, J; Fink, M E; Mangat, H S; Segal, A Z; Mushlin, A I; Sanelli, P C

2014-03-01

In recent years CTP has been used as a complementary diagnostic tool in the evaluation of delayed cerebral ischemia and vasospasm. Our aim was to determine the test characteristics of CTP for detecting delayed cerebral ischemia and vasospasm in SAH, and then to apply Bayesian analysis to identify subgroups for its appropriate use. Our retrospective cohort comprised consecutive patients with SAH and CTP performed between days 6 and 8 following aneurysm rupture. Delayed cerebral ischemia was determined according to primary outcome measures of infarction and/or permanent neurologic deficits. Vasospasm was determined by using DSA. The test characteristics of CTP and its 95% CIs were calculated. Graphs of conditional probabilities were constructed by using Bayesian techniques. Local treatment thresholds (posttest probability of delayed cerebral ischemia needed to initiate induced hypertension, hypervolemia, and hemodilution or intra-arterial therapy) were determined via a survey of 6 independent neurologists. Ninety-seven patients with SAH were included in the study; 39% (38/97) developed delayed cerebral ischemia. Qualitative CTP deficits were seen in 49% (48/97), occurring in 84% (32/38) with delayed cerebral ischemia and 27% (16/59) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.84 (0.73-0.96), 0.73 (0.62-0.84), 0.67 (0.51-0.79), and 0.88 (0.74-0.94), respectively. A subgroup of 57 patients underwent DSA; 63% (36/57) developed vasospasm. Qualitative CTP deficits were seen in 70% (40/57), occurring in 97% (35/36) with vasospasm and 23% (5/21) without. The sensitivity, specificity, and positive and negative predictive values (95% CI) for CTP were 0.97 (0.92-1.0), 0.76 (0.58-0.94), 0.88 (0.72-0.95), and 0.94 (0.69-0.99), respectively. Treatment thresholds were determined as 30% for induced hypertension, hypervolemia, and hemodilution and 70% for intra-arterial therapy. Positive CTP findings identify patients who should be carefully considered for induced hypertension, hypervolemia, and hemodilution and/or intra-arterial therapy while negative CTP findings are useful in guiding a no-treatment decision.

Using higher doses to compensate for tubing residuals in extended-infusion piperacillin-tazobactam.

PubMed

Lam, Wendy J; Bhowmick, Tanaya; Gross, Alan; Vanschooneveld, Trevor C; Weinstein, Melvin P

2013-06-01

To mathematically assess drug losses due to infusion line residuals and evaluate methods to compensate for drug loss due to residual volumes in intravenous pump tubing. Literature was accessed through Ovid MEDLINE (1996-February 2013), using combinations of the search terms tubing residuals, residual volume, residual medication, intravenous infusions, intravenous injections, piperacillin, piperacillin-tazobactam, β-lactams, equipment design, infusion pumps, extended infusion, extended administration, and prolonged infusion. In addition, select reference citations from publications identified were reviewed. All articles that involved extended-infusion piperacillin-tazobactam implementation strategies were included in the review. Infusion pump characteristics and tubing residuals can affect extended-infusion piperacillin-tazobactam dosing strategies. Two studies addressing tubing residuals were identified. Both studies recommended increasing infusion volumes to compensate for tubing residuals. One study also recommended decreasing infusion-line dead space by using alternative infusion pump systems. Study calculations suggest that higher doses of piperacillin-tazobactam may be used to account for medication left in tubing residuals if alternative infusion pump systems cannot be obtained, and increased infusion volumes are not an option. Extended-infusion piperacillin-tazobactam has been used as a method of maximizing pharmacodynamic target attainment. Use of higher doses of piperacillin-tazobactam may be a reasonable method to compensate for drug loss due to residual volumes in large-bore intravenous pump tubing.

Clinical and economic impact of infliximab one-hour infusion protocol in patients with inflammatory bowel diseases: A multicenter study

PubMed Central

Viola, Anna; Costantino, Giuseppe; Privitera, Antonino Carlo; Bossa, Fabrizio; Lauria, Angelo; Grossi, Laurino; Principi, Maria Beatrice; Della Valle, Nicola; Cappello, Maria

2017-01-01

AIM To assess the impact of short infliximab (IFX) infusion on hospital resource utilization and costs. METHODS All inflammatory bowel diseases (IBD) patients who received IFX 1 h infusion from March 2007 to September 2014 in eight centers from Southern Italy were included in the analysis. Demographic, clinical and infusion related data were collected. The potential benefits related to the short infusion protocol were assessed both in terms of time saving and increased infusion unit capacity. In addition, indirect patient-related cost savings were evaluated. RESULTS One hundred and twenty-five patients were recruited (64 with ulcerative colitis and 61 with Crohn’s disease). Median duration of disease was of 53 mo and mean age of pts at diagnosis was of 34 years (SD: ± 13). Adverse infusion reactions were reported in less than 4% both before and after short infusion. The total number of infusions across the selected centers was of 2501 (30.5% short infusions). In the analyzed cohort, 1143 h were saved (762 in the infusion and 381 in observation phases) through the rapid IFX infusion protocol. This time saving (-15% compared to the standard protocol in infusion phase) represents, from the hospital perspective, an opportunity to optimize infusion unit capacity by allocating the saved time in alternative cost-effective treatments. This is the case of opportunity cost that represents the value of forgone benefit which could be obtained from a resource in its next-best alternative use. Hence, an extra hour of infusion in the case of standard 2-h IFX represents a loss in opportunity to provide other cost effective services. The analysis showed that the short infusion increased the infusion units capacity up to 50% on days when the IFX infusions were scheduled (infusion phase). Furthermore, the analysis showed that the short IFX infusion protocol leads to time savings also in the post-infusion phase (observation) leading to a time saving of 10% on average among the analyzed centers. Finally, the short infusion protocol has been demonstrated to lead to indirect cost savings of €138/patient (average -€17.300 on the whole cohort). CONCLUSION A short IFX infusion protocol can be considered time and cost saving in comparison to the standard infusion protocol both from the hospital’s perspective, as it contributes to increase infusion units capacity, and the patients’ perspective, as it reduces indirect costs and the impact of treatment on everyday life and work productivity. PMID:28533923

Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.

PubMed Central

Staumont, G; Fioramonti, J; Frexinos, J; Bueno, L

1988-01-01

The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes varied from 5 to 15 mg/kg. Intracolonic sennosides at the minimal effective dose and at 30 mg/kg reproduced the effects of oral sennosides, but with a shorter latency (0.5-1.5 h). Intracolonic PGE2 (100 micrograms/kg) in viscous gel medium or intra-arterial PGE2 (10 micrograms/h) inhibited colonic motility and induced giant contractions often associated with defecation. The colonic motor changes induced by intracolonic sennosides at the minimal effective dose, but not those induced by intracolonic PGE2, were blocked by intra-arterial indomethacin (10 micrograms/h) or piroxicam (5 micrograms/h). These results suggest that colonic motor actions of sennosides are mediated through a local prostaglandins synthesis, as they were blocked by cyclooxygenase inhibitor and reproduced by PGE2. PMID:3197991

[Complications of endonasal surgery of the paranasal sinuses. Special anatomy, pathomechanisms, surgical management].

PubMed

Rauchfuss, A

1990-09-01

Statistics show that there is no significant increase in complications in endonasal sinus surgery of the ethmoid or sphenoid as compared to paranasal or transantral procedures. Exact anatomical knowledge of the nasal cavity, the paranasal sinuses and related structures is essential for assessment and management in iatrogenic complications, which are divided in three groups, according to characteristic topographic implications: orbito-ocular, vascular, encephalomeningeal. Orbito-ocular complications are managed by decompression of the orbit using the paranasal approach. Direct lesions of the optic nerve in ethmoid- or sphenoid-sinus surgery are extremely rare and are due to an abnormal nervous course. Vascular complications in the branches of the external carotid artery require local procedures (e.g. transantral ligature of the sphenopalatine artery). In some cases an intra-arterial embolization using supra-selective angiography is more effective. Massive bleeding from lesions of the internal carotid artery is stopped by placement of a balloon catheter combined with a transfemoral intra-arterial digital subtraction technique. Iatrogenic dura defects in the frontal skull base can be managed easily once the lesion has been exactly and clearly localized. Adequate control of the frontobase including the orbit, optic nerve and related vascular and nervous structures is achieved by the extracranial subfrontal paranasal (Killian incision) approach, if endoscopic or endonasal microscopic repair is ineffective.

Management of Postembolization Syndrome Following Hepatic Transarterial Chemoembolization for Primary or Metastatic Liver Cancer.

PubMed

Blackburn, Helen; West, Sandra

2016-01-01

Transarterial chemoembolization (TACE) is an established treatment in managing liver primary neoplasms or liver metastases. Postembolization syndrome (PES) is a common adverse event defined as fever without associated sepsis, pain in the right upper quadrant, and nausea and/or vomiting. This integrative review aims to identify effective management strategies for PES or one of its characterizing symptoms (fever, pain, and nausea and/or vomiting). Searches of electronic databases MEDLINE, EMBASE, and CINAHL were conducted. Fifteen articles were identified for inclusion. Seven addressed all symptoms of PES, and 8 studies focused on individual symptoms of PES. Interventions identified are intra-arterial lidocaine, oral and intravenous analgesics, steroids, wrist-ankle acupuncture, antibiotics, and 5-HT3 receptor antagonists. Findings are explicated according to individual symptoms of PES. Intra-arterial lidocaine, steroids, and a 5-HT3 receptor antagonist are found to offer potential benefit in the management of PES symptoms. A number of interventions have shown potential benefit in the management of PES. A systemic approach using combination therapy is necessary to effectively manage characterizing symptoms. Further research is needed to determine the impact of primary disease site, TACE technique, and chemotherapeutic agent on PES. Oncology nurses are uniquely placed to undertake thorough patient assessment after TACE and implement early intervention to effectively manage PES.

Continuous neonatal blood gas monitoring using a multiparameter intra-arterial sensor

PubMed Central

Morgan, C; Newell, S; Ducker, D; Hodgkinson, J; White, D; Morley, C; Church, J

1999-01-01

AIMS—To compare arterial blood gas (ABG) readings obtained with a multiparameter intra-arterial sensor with those from an ABG analyser.
METHODS—An MPIAS with the ability to measure continuously pH, PaCO2, and PaO2 was introduced via an umbilical arterial catheter in 27 neonates requiring intensive care. They underwent 3260 hours of MPIAS monitoring, during which 753 ABG readings were performed.
RESULTS—Overall bias (mean difference: MPIAS-ABG) and precision (standard deviation of differences) values were: −0.002 and 0.022,respectively, for pH; +0.26 and 0.52 for PaCO2 (kPa); and −0.19 and 0.99 for PaO2 (kPa). This gave 95% limits of agreement as: −0.047 to +0.042 for pH, −0.76 to +1.28 kPa for PaCO2, and −2.13 to +1.75 kPa for PaO2. For each variable, precision across readings from the same individual was better than overall precision for all data. No complications related to the use of the catheter were observed.
CONCLUSIONS—Continuous MPIAS ABG monitoring is an exciting development, with the potential to reduce blood transfusions and improve ABG homeostasis.

 PMID:10325783

Symptomatic Vasospasms as a Life-Threatening Complication After Transsphenoidal Surgery.

PubMed

Osterhage, Katharina; Czorlich, Patrick; Burkhardt, Till R; Rotermund, Roman; Grzyska, Ulrich; Flitsch, Jörg

2018-02-01

To identify symptomatic vasospasms as a rare complication after transsphenoidal surgery, with emphasis on management and outcomes. In this retrospective study, the medical records of 1997 patients who underwent microscopic transsphenoidal surgery at our hospital between 2008 and 2016 were analyzed regarding postoperative vasospasm events, clinical management, and neurologic outcomes. Four patients (0.2%) were identified who developed neurologic deficits in the postoperative phase caused by proven vasospasms due to subarachnoid hemorrhage (SAH). All 4 patients were treated according to current state-of-the-art recommendations for SAH-triggered vasospasms and, as ultima ratio, intra-arterial spasmolysis. Nonetheless, all patients developed multilocular ischemic infarctions. Three patients recovered with no or only slight neurologic deficits (2 with a Glasgow Outcome Score [GOS] of 5; 1 with a GOS of 4), and 1 patient died, at 24 days after surgery. Although a rare complication, vasospasms after transsphenoidal surgery can lead to severe and multilocular ischemic infarctions with a wide variety of neurologic impairments. This rare complication should be considered in patients with unexpected postoperative neurologic deficits. Computed tomography (CT)/magnetic resonance imaging and (contrast-enhanced) CT/magnetic resonance angiography are appropriate diagnostic tools. Treatment of vasospasms, including the option of intra-arterial spasmolysis, should not be delayed. Copyright © 2017. Published by Elsevier Inc.

Paediatric electronic infusion calculator: An intervention to eliminate infusion errors in paediatric critical care.

PubMed

Venkataraman, Aishwarya; Siu, Emily; Sadasivam, Kalaimaran

2016-11-01

Medication errors, including infusion prescription errors are a major public health concern, especially in paediatric patients. There is some evidence that electronic or web-based calculators could minimise these errors. To evaluate the impact of an electronic infusion calculator on the frequency of infusion errors in the Paediatric Critical Care Unit of The Royal London Hospital, London, United Kingdom. We devised an electronic infusion calculator that calculates the appropriate concentration, rate and dose for the selected medication based on the recorded weight and age of the child and then prints into a valid prescription chart. Electronic infusion calculator was implemented from April 2015 in Paediatric Critical Care Unit. A prospective study, five months before and five months after implementation of electronic infusion calculator, was conducted. Data on the following variables were collected onto a proforma: medication dose, infusion rate, volume, concentration, diluent, legibility, and missing or incorrect patient details. A total of 132 handwritten prescriptions were reviewed prior to electronic infusion calculator implementation and 119 electronic infusion calculator prescriptions were reviewed after electronic infusion calculator implementation. Handwritten prescriptions had higher error rate (32.6%) as compared to electronic infusion calculator prescriptions (<1%) with a p  < 0.001. Electronic infusion calculator prescriptions had no errors on dose, volume and rate calculation as compared to handwritten prescriptions, hence warranting very few pharmacy interventions. Use of electronic infusion calculator for infusion prescription significantly reduced the total number of infusion prescribing errors in Paediatric Critical Care Unit and has enabled more efficient use of medical and pharmacy time resources.

21 CFR 880.6990 - Infusion stand.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Infusion stand. 880.6990 Section 880.6990 Food and....6990 Infusion stand. (a) Identification. The infusion stand is a stationary or movable stand intended to hold infusion liquids, infusion accessories, and other medical devices. (b) Classification. Class...

21 CFR 880.6990 - Infusion stand.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infusion stand. 880.6990 Section 880.6990 Food and....6990 Infusion stand. (a) Identification. The infusion stand is a stationary or movable stand intended to hold infusion liquids, infusion accessories, and other medical devices. (b) Classification. Class...

Ramped-rate vs continuous-rate infusions: An in vitro comparison of convection enhanced delivery protocols.

PubMed

Schomberg, Dominic; Wang, Anyi; Marshall, Hope; Miranpuri, Gurwattan; Sillay, Karl

2013-04-01

Convection enhanced delivery (CED) is a technique using infusion convection currents to deliver therapeutic agents into targeted regions of the brain. Recently, CED is gaining significant acceptance for use in gene therapy of Parkinson's disease (PD) employing direct infusion into the brain. CED offers advantages in that it targets local areas of the brain, bypasses the blood-brain barrier (BBB), minimizes systemic toxicity of the therapeutics, and allows for delivery of larger molecules that diffusion driven methods cannot achieve. Investigating infusion characteristics such as backflow and morphology is important in developing standard and effective protocols in order to successfully deliver treatments into the brain. Optimizing clinical infusion protocols may reduce backflow, improve final infusion cloud morphology, and maximize infusate penetrance into targeted tissue. The purpose of the current study was to compare metrics during ramped-rate and continuous-rate infusions using two different catheters in order to optimize current infusion protocols. Occasionally, the infusate refluxes proximally up the catheter tip, known as backflow, and minimizing this can potentially reduce undesirable effects in the clinical setting. Traditionally, infusions are performed at a constant rate throughout the entire duration, and backflow is minimized only by slow infusion rates, which increases the time required to deliver the desired amount of infusate. In this study, we investigate the effects of ramping and various infusion rates on backflow and infusion cloud morphology. The independent parameters in the study are: ramping, maximum infusion rate, time between rate changes, and increments of rate changes. Backflow was measured using two methods: i) at the point of pressure stabilization within the catheter, and ii) maximum backflow as shown by video data. Infusion cloud morphology was evaluated based on the height-to-width ratio of each infusion cloud at the end of each experiment. Results were tabulated and statistically analyzed to identify any significant differences between protocols. The experimental results show that CED rampedrate infusion protocols result in smaller backflow distances and more spherical cloud morphologies compared to continuous-rate infusion protocols ending at the same maximum infusion rate. Our results also suggest internal-line pressure measurements can approximate the time-point at which backflow ceases. Our findings indicate that ramping CED infusion protocols can potentially minimize backflow and produce more spherical infusion clouds. However, further research is required to determine the strength of this correlation, especially in relation to maximum infusion rates.

Infusion-line pressure as a real-time monitor of convection-enhanced delivery in pre-clinical models.

PubMed

Lam, Miu Fei; Foo, Stacy W L; Thomas, Meghan G; Lind, Christopher R P

2014-01-15

Acute convection-enhanced delivery (CED) is a neurosurgical delivery technique that allows for precise and uniform distribution of an infusate to a brain structure. It remains experimental due to difficulties in ensuring successful delivery. Real-time monitoring is able to provide immediate feedback on cannula placement, infusate distribution, and if the infusion is proceeding as planned or is failing due to reflux or catheter obstruction. Pressure gradient is the driving force behind CED, with the infusion pressure being directly proportional to the flow-rate. The aim of this study was to assess the feasibility of using infusion-line pressure profiling to distinguish in real-time between succeeding and failing CED infusions. To do so we delivered cresyl violet dye at 0.5, 1.0 and 2.0 μl/min via CED in vitro using 0.6% agarose gel and in vivo to the rat striatum. Infusions that failed in agarose gel models could only be differentiated late during the procedures. In the rat in vivo model, the infusion-line profiles of obstructed infusions were not distinctive from those of successful infusions. Intraoperative magnetic resonance imaging (MRI) is used for real-time visualisation of cannula placement and infusate distribution. Particularly for animal pre-clinical work, it would be advantageous to supplement MRI with a cheap, accessible technique to monitor infusions and provide a real-time measure of infusion success or failure. Infusion-line pressure monitoring was of limited value in identifying successful CED with small volume infusions, whilst its utility for large volume infusion remains unknown. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Structural determinants for the inhibitory ligands of orotidine-5′-monophosphate decarboxylase

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

Meza-Avina, Maria Elena; Wei, Lianhu; Liu, Yan

2010-06-14

In recent years, orotidine-5{prime}-monophosphate decarboxylase (ODCase) has gained renewed attention as a drug target. As a part of continuing efforts to design novel inhibitors of ODCase, we undertook a comprehensive study of potent, structurally diverse ligands of ODCase and analyzed their structural interactions in the active site of ODCase. These ligands comprise of pyrazole or pyrimidine nucleotides including the mononucleotide derivatives of pyrazofurin, barbiturate ribonucleoside, and 5-cyanouridine, as well as, in a computational approach, 1,4-dihydropyridine-based non-nucleoside inhibitors such as nifedipine and nimodipine. All these ligands bind in the active site of ODCase exhibiting distinct interactions paving the way to designmore » novel inhibitors against this interesting enzyme. We propose an empirical model for the ligand structure for rational modifications in new drug design and potentially new lead structures.« less

Episodic migraines in children: limited evidence on preventive pharmacological treatments.

PubMed

Shamliyan, Tatyana A; Kane, Robert L; Ramakrishnan, Rema; Taylor, Frederick R

2013-10-01

The authors conducted a systematic literature review of preventive pharmacological treatments for episodic childhood migraines searching several databases through May 20, 2012. Episodic migraine prevention was examined in 24 publications of randomized controlled trials that enrolled 1578 children in 16 nonrandomized studies. Single randomized controlled trials provided low-strength evidence that propranolol would result in complete cessation of migraine attacks in 713 per 1000 children treated (95% confidence interval, 452-974); trazodone and nimodipine decreased migraine days, while topiramate, divalproex, and clonidine were no more effective than placebo in preventing migraines. Migraine prevention with multidisciplinary drug management was not sustained at 6 months. Divalproex resulted in treatment discontinuation due to adverse effects, and topiramate increased the risk of paresthesia, upper respiratory tract infection, and weight loss. Long-term preventive benefits and improvement in disability and quality of life are unknown. No studies examined quality of life or provided evidence for individualized treatment decisions.

Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer's disease.

PubMed

Marco-Contelles, José; León, Rafael; de los Ríos, Cristóbal; Samadi, Abdelouahid; Bartolini, Manuela; Andrisano, Vincenza; Huertas, Oscar; Barril, Xavier; Luque, F Javier; Rodríguez-Franco, María I; López, Beatriz; López, Manuela G; García, Antonio G; Carreiras, María do Carmo; Villarroya, Mercedes

2009-05-14

Tacripyrines (1-14) have been designed by combining an AChE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop a multitarget therapeutic strategy to confront AD. Tacripyrines are selective and potent AChE inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity of compound 11 (IC(50) 105 +/- 15 nM) is associated to a 30.7 +/- 8.6% inhibition of the proaggregating action of AChE on the Abeta and a moderate inhibition of Abeta self-aggregation (34.9 +/- 5.4%). Molecular modeling indicates that binding of compound 11 to the AChE PAS mainly involves the (R)-11 enantiomer, which also agrees with the noncompetitive inhibition mechanism exhibited by p-methoxytacripyrine 11. Tacripyrines are neuroprotective agents, show moderate Ca(2+) channel blocking effect, and cross the blood-brain barrier, emerging as lead candidates for treating AD.

Insufficient sleep is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation.

PubMed

Bain, Anthony R; Weil, Brian R; Diehl, Kyle J; Greiner, Jared J; Stauffer, Brian L; DeSouza, Christopher A

2017-10-01

Habitual short nightly sleep duration is associated with increased atherosclerotic cardiovascular disease risk and morbidity. Vascular endothelial dysfunction represents an important mechanism that may underlie this heightened cardiovascular risk. Impaired endothelium-dependent vasodilation, particularly NO-mediated vasodilation, contributes to the development and progression of atherosclerotic vascular disease and acute vascular events. We tested the hypothesis that chronic insufficient sleep is associated with impaired NO-mediated endothelium-dependent vasodilation in middle-aged adults. Thirty adult men were studied: 15 with normal nightly sleep duration (age: 58 ± 2 y; sleep duration: 7.7 ± 0.2 h/night) and 15 with short nightly sleep duration (55 ± 2 y; 6.1 ± 0.2 h/night). Forearm blood flow (FBF) responses to intra-arterial infusion of acetylcholine, in the absence and presence of the endothelial NO synthase inhibitor N G -monomethyl-L-arginine (L-NMMA), as well as responses to sodium nitroprusside, were determined by strain-gauge venous occlusion plethysmography. The FBF response to acetylcholine was lower (∼20%; p<0.05) in the short sleep duration group (from 4.6 ± 0.3 to 11.7 ± 1.0 ml/100 ml tissue/min) compared with normal sleep duration group (from 4.4 ± 0.3 to 14.5 ± 0.5 ml/100 ml tissue/min). L-NMMA significantly reduced the FBF response to acetylcholine in the normal sleep duration group (∼40%), but not the short sleep duration group. There were no group differences in the vasodilator response to sodium nitroprusside. These data indicate that short nightly sleep duration is associated with endothelial-dependent vasodilator dysfunction due, in part, to diminished NO bioavailability. Impaired NO-mediated endothelium-dependent vasodilation may contribute to the increased cardiovascular risk with insufficient sleep. Copyright © 2017 Elsevier B.V. All rights reserved.

Systemic administration of 3-bromopyruvate reveals its interaction with serum proteins in a rat model.

PubMed

Kunjithapatham, Rani; Geschwind, Jean-Francois H; Rao, Pramod P; Boronina, Tatiana N; Cole, Robert N; Ganapathy-Kanniappan, Shanmugasundaram

2013-07-17

3-bromopyruvate (3-BrPA) is a glycolytic inhibitor that affects cancer cells by targeting energy metabolism. Preclinical reports have established that a 1.75 mM dose of 3-BrPA is effective and sufficient to inhibit tumor growth when administered under a loco-regional approach (intraarterial and intratumoral). This loco-regional therapeutic dose was found to be nontoxic when given systemically as well. Yet, the mechanism underlying this lack of toxicity of 1.75 mM 3-BrPA during systemic delivery is unknown. Here, we investigated the mechanism associated with the lack of organ toxicity when 1.75 mM 3-BrPA was administered systemically using radiolabeled (14C)-3-BrPA in Sprague-Dawley rats. Data obtained from tissue-autoradiography of rats infused with 14C-3-BrPA showed strong 14C-signal in tissue sections of various organs except the brain corroborating that 3-BrPA does not cross the blood-brain barrier. Significantly, Hematoxylin & Eosin staining and apoptosis assay of tissue sections positive for 14C-signal showed no signs of toxicity or apoptosis. Convincingly, the 14C-signal observed in tissue-autoradiography emanates from 3-BrPA that is non-reactive or non-toxic, hence we further investigated whether the lack of toxicity is due to its interaction or alkylation with serum components. Analysis of serum proteins by 1D and 2D-gel electrophoretic autoradiography showed that 14C-BrPA selectively binds to peptides of molecular mass ~50-60 kDa. Mass spectrometry data suggested that 14C-BrPA could interact with alpha1-antitrypsin and a peptide of albuminoid-family. Our data indicate that selective interaction of 3-BrPA with serum proteins could contribute to the apparent lack of tissue-toxicity at the indicated close when the drug is given systematically in Sprague-Dawley rats.

Systemic administration of 3-bromopyruvate reveals its interaction with serum proteins in a rat model

PubMed Central

2013-01-01

Background 3-bromopyruvate (3-BrPA) is a glycolytic inhibitor that affects cancer cells by targeting energy metabolism. Preclinical reports have established that a 1.75 mM dose of 3-BrPA is effective and sufficient to inhibit tumor growth when administered under a loco-regional approach (intraarterial and intratumoral). This loco-regional therapeutic dose was found to be nontoxic when given systemically as well. Yet, the mechanism underlying this lack of toxicity of 1.75 mM 3-BrPA during systemic delivery is unknown. Here, we investigated the mechanism associated with the lack of organ toxicity when 1.75 mM 3-BrPA was administered systemically using radiolabeled (14C)-3-BrPA in Sprague–Dawley rats. Findings Data obtained from tissue-autoradiography of rats infused with 14C-3-BrPA showed strong 14C-signal in tissue sections of various organs except the brain corroborating that 3-BrPA does not cross the blood–brain barrier. Significantly, Hematoxylin & Eosin staining and apoptosis assay of tissue sections positive for 14C-signal showed no signs of toxicity or apoptosis. Convincingly, the 14C-signal observed in tissue-autoradiography emanates from 3-BrPA that is non-reactive or non-toxic, hence we further investigated whether the lack of toxicity is due to its interaction or alkylation with serum components. Analysis of serum proteins by 1D and 2D-gel electrophoretic autoradiography showed that 14C-BrPA selectively binds to peptides of molecular mass ~50-60 kDa. Mass spectrometry data suggested that 14C-BrPA could interact with alpha1-antitrypsin and a peptide of albuminoid-family. Conclusion Our data indicate that selective interaction of 3-BrPA with serum proteins could contribute to the apparent lack of tissue-toxicity at the indicated close when the drug is given systematically in Sprague–Dawley rats. PMID:23866825

Reduced mechanosensitivity of duodenal vagal afferent neurons after an acute switch from milk-based to plant-based diets in anaesthetized pigs.

PubMed

Bligny, D; Blat, S; Chauvin, A; Guérin, S; Malbert, C-H

2005-06-01

Acute changes in diet composition and/or origin alter gastric emptying and gastrointestinal motility. One of the hypotheses explaining these alterations involves changes in the sensitivity of duodenal vagal sensory neurons. The aim of this study was to evaluate the characteristics of multimodal duodenal vagal sensory neurons in 20 pigs feed either with milk-based or plant-based diets of identical caloric content. Twenty duodenal vagal afferents were recorded in anesthetized animal from the cervical vagus using the single fiber method. 10 pigs were fed with a milk-based diet (MD) for one month while the diet of the 10 other pigs was changed for plant-based diet (PD) the day preceding the recording session. The behavior of the receptors was tested in basal resting conditions and after challenges with duodenal intralipid and close intra-arterial injection of CCK, 5-HT or capsaicin with and without isovolumetric duodenal distensions at 20, 40 and 60 mmHg. All receptors were slowly adapting C type fiber with a receptor field located 6-7 cm distal to the pylorus. The rate of discharge during distension (20, 40 and 60 mmHg) combined with duodenal intralipid was significantly larger for MD compared with PD. Similarly, the rate of discharge observed during distensions performed with CCK and with 5-HT were greater for MD compared with PD while CCK and 5-HT without distension were equally stimulating for MD and PD. No significant difference was found between groups during capsaicin infusion irrespective of the stimulating pressure. In conclusion, a switch to plant-based diet, when compared to a milk-based diet, results in an overall decrease in mechanical sensitivity of duodenal neurons during lipid, 5HT and CCK challenges, but not in basal conditions or after capsaicin. This reduced sensitivity to distension may explain the diet-induced alteration of gastric emptying that is controlled primarily through a vago-vagal reflex.

Effects of Oral Lycopene Supplementation on Vascular Function in Patients with Cardiovascular Disease and Healthy Volunteers: A Randomised Controlled Trial

PubMed Central

Gajendragadkar, Parag R.; Hubsch, Annette; Mäki-Petäjä, Kaisa M.; Serg, Martin; Wilkinson, Ian B.; Cheriyan, Joseph

2014-01-01

Aims The mechanisms by which a ‘Mediterranean diet’ reduces cardiovascular disease (CVD) burden remain poorly understood. Lycopene is a potent antioxidant found in such diets with evidence suggesting beneficial effects. We wished to investigate the effects of lycopene on the vasculature in CVD patients and separately, in healthy volunteers (HV). Methods and Results We randomised 36 statin treated CVD patients and 36 healthy volunteers in a 2∶1 treatment allocation ratio to either 7 mg lycopene or placebo daily for 2 months in a double-blind trial. Forearm responses to intra-arterial infusions of acetylcholine (endothelium-dependent vasodilatation; EDV), sodium nitroprusside (endothelium-independent vasodilatation; EIDV), and NG-monomethyl-L-arginine (basal nitric oxide (NO) synthase activity) were measured using venous plethysmography. A range of vascular and biochemical secondary endpoints were also explored. EDV in CVD patients post-lycopene improved by 53% (95% CI: +9% to +93%, P = 0.03 vs. placebo) without changes to EIDV, or basal NO responses. HVs did not show changes in EDV after lycopene treatment. Blood pressure, arterial stiffness, lipids and hsCRP levels were unchanged for lycopene vs. placebo treatment groups in the CVD arm as well as the HV arm. At baseline, CVD patients had impaired EDV compared with HV (30% lower; 95% CI: −45% to −10%, P = 0.008), despite lower LDL cholesterol (1.2 mmol/L lower, 95% CI: −1.6 to −0.9 mmol/L, P<0.001). Post-therapy EDV responses for lycopene-treated CVD patients were similar to HVs at baseline (2% lower, 95% CI: −30% to +30%, P = 0.85), also suggesting lycopene improved endothelial function. Conclusions Lycopene supplementation improves endothelial function in CVD patients on optimal secondary prevention, but not in HVs. Trial Registration ClinicalTrials.gov NCT01100385 PMID:24911964

Exaggerated Exercise Blood Pressure Response and Future Cardiovascular Disease.

PubMed

Tzemos, Nikolaos; Lim, Pitt O; Mackenzie, Isla S; MacDonald, Thomas M

2015-11-01

Exaggerated blood pressure (BP) response to exercise predicts future hypertension. However, there is considerable lack of understanding regarding the mechanism of how this abnormal response is generated, and how it relates to the future establishment of cardiovascular disease. The authors studied 82 healthy male volunteers without cardiovascular risk factors. The participants were categorized into two age-matched groups depending on their exercise systolic BP (ExSBP) rise after 3 minutes of exercise using a submaximal step test: exaggerated ExSBP group (hyper-responders [peak SBP ≥ 180 mm Hg]) and low ExSBP responder group (hypo-responders [peak SBP <180 mm Hg]). Forearm venous occlusion plethysmography and intra-arterial infusions of acetylcholine (ACh), N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside (SNP), and norepinephrine (NE) were used to assess vascular reactivity. Proximal aortic compliance was assessed with ultrasound, and neurohormonal blood sampling was performed at rest and during peak exercise. The hyper-responder group exhibited a significantly lower increase in forearm blood flow (FBF) with ACh compared with the hypo-responder group (ΔFBF 215% [14] vs 332.3% [28], mean [standard error of the mean]; P<.001), as well as decreased proximal aortic compliance. The vasoconstrictive response to L-NMMA was significantly impaired in the hyper-responder group in comparison to the hypo-responder group (ΔFBF -40.2% [1.6] vs -50.2% [2.6]; P<.05). In contrast, the vascular response to SNP and NE were comparable in both groups. Peak exercise plasma angiotensin II levels were significantly higher in the hyper-responder group (31 [1] vs 23 [2] pg/mL, P=.01). An exaggerated BP response to exercise is related to endothelial dysfunction, decreased proximal aortic compliance, and increased exercise-related neurohormonal activation, the constellation of which may explain future cardiovascular disease. © 2015 Wiley Periodicals, Inc.

Reductions in carotid chemoreceptor activity with low-dose dopamine improves baroreflex control of heart rate during hypoxia in humans.

PubMed

Mozer, Michael T; Holbein, Walter W; Joyner, Michael J; Curry, Timothy B; Limberg, Jacqueline K

2016-07-01

The purpose of the present investigation was to examine the contribution of the carotid body chemoreceptors to changes in baroreflex control of heart rate with exposure to hypoxia. We hypothesized spontaneous cardiac baroreflex sensitivity (scBRS) would be reduced with hypoxia and this effect would be blunted when carotid chemoreceptor activity was reduced with low-dose dopamine. Fifteen healthy adults (11 M/4 F) completed two visits randomized to intravenous dopamine or placebo (saline). On each visit, subjects were exposed to 5-min normoxia (~99% SpO2), followed by 5-min hypoxia (~84% SpO2). Blood pressure (intra-arterial catheter) and heart rate (ECG) were measured continuously and scBRS was assessed by spectrum and sequence methodologies. scBRS was reduced with hypoxia (P < 0.01). Using the spectrum analysis approach, the fall in scBRS with hypoxia was attenuated with infusion of low-dose dopamine (P < 0.01). The decrease in baroreflex sensitivity to rising pressures (scBRS "up-up") was also attenuated with low-dose dopamine (P < 0.05). However, dopamine did not attenuate the decrease in baroreflex sensitivity to falling pressures (scBRS "down-down"; P > 0.05). Present findings are consistent with a reduction in scBRS with systemic hypoxia. Furthermore, we show this effect is partially mediated by the carotid body chemoreceptors, given the fall in scBRS is attenuated when activity of the chemoreceptors is reduced with low-dose dopamine. However, the improvement in scBRS with dopamine appears to be specific to rising blood pressures. These results may have important implications for impairments in baroreflex function common in disease states of acute and/or chronic hypoxemia, as well as the experimental use of dopamine to assess such changes. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

TREATMENT OF MICROVASCULAR MICRO-EMBOLIZATION USING MICROBUBBLES AND LONG-TONE-BURST ULTRASOUND: AN IN VIVO STUDY

PubMed Central

Pacella, John J.; Brands, Judith; Schnatz, Frederick G.; Black, John J.; Chen, Xucai; Villanueva, Flordeliza S.

2015-01-01

Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 5 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound–microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound–microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction. PMID:25542487

Tumor Response and Apoptosis of N1-S1 Rodent Hepatomas in Response to Intra-arterial and Intravenous Benzamide Riboside

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

McLennan, Gordon, E-mail: gmclenna@me.com; Bennett, Stacy L.; Ju, Shenghong

2012-06-15

Purpose: Benzamide riboside (BR) induces tumor apoptosis in multiple cell lines and animals. This pilot study compares apoptosis and tumor response in rat hepatomas treated with hepatic arterial BR (IA) or intravenous (IV) BR. Methods: A total of 10{sup 6} N1-S1 cells were placed in the left hepatic lobes of 15 Sprague-Dawley rats. After 2 weeks, BR (20 mg/kg) was infused IA (n = 5) or IV (n = 5). One animal in each group was excluded for technical factors, which prevented a full dose administration (1 IA and 1 IV). Five rats received saline (3 IA and 2 IV).more » Animals were killed after 3 weeks. Tumor volumes after IA and IV treatments were analyzed by Wilcoxon rank sum test. The percentage of tumor and normal liver apoptosis was counted by using 10 fields of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-stained slides at 40 Multiplication-Sign magnification. The percentage of apoptosis was compared between IV and IA administrations and with saline sham-treated rats by the Wilcoxon rank sum test. Results: Tumors were smaller after IA treatment, but this did not reach statistical significance (0.14 IA vs. 0.57 IV; P = 0.138). There was much variability in percentage of apoptosis and no significant difference between IA and IV BR (44.49 vs. 1.52%; P = 0.18); IA BR and saline (44.49 vs. 33.83%; P = 0.66); or IV BR and saline (1.52 vs. 193%; P = 0.18). Conclusions: Although differences in tumor volumes did not reach statistical significance, there was a trend toward smaller tumors after IA BR than IV BR in this small pilot study. Comparisons of these treatment methods will require a larger sample size and repeat experimentation.« less

Serotonin and cholecystokinin synergistically stimulate rat vagal primary afferent neurones

PubMed Central

Li, Y; Wu, X Y; Owyang, C

2004-01-01

Recent studies indicate that cholecystokinin (CCK) and serotonin (5-hydroxytryptamine, 5-HT) act via vagal afferent fibres to mediate gastrointestinal functions. In the present study, we characterized the interaction between CCK and 5-HT in the vagal primary afferent neurones. Single neuronal discharges of vagal primary afferent neurones innervating the duodenum were recorded from rat nodose ganglia. Two groups of nodose ganglia neurones were identified: group A neurones responded to intra-arterial injection of low doses of cholecystokinin octapeptide (CCK-8; 10–60 pmol); group B neurones responded only to high doses of CCK-8 (120–240 pmol), and were also activated by duodenal distention. CCK-JMV-180, which acts as an agonist in high-affinity states and as an antagonist in low-affinity states, dose dependently stimulated group A neurones, but inhibited the effect of the high doses of CCK-8 on group B neurones. Duodenal perfusion of 5-HT evoked dose-dependent increases in nodose neuronal discharges. Some neurones that responded to 5-HT showed no response to either high or low doses of CCK-8. A separate group of nodose neurones that possessed high-affinity CCK type A (CCK-A) receptors also responded to luminal infusion of 5-HT. Further, a subthreshold dose of CCK-8 (i.e. 5 pmol) produced no measurable electrophysiological effects but it augmented the neuronal responses to 5-HT. This potentiation effect of CCK-8 was eliminated by CR 1409. From these results we concluded that the vagal nodose ganglion contains neurones that may possess only high- or low-affinity CCK-A receptors or 5-HT3 receptors. Some neurones that express high-affinity CCK-A receptors also express 5-HT3 receptors. Pre-exposure to luminal 5-HT may augment the subsequent response to a subthreshold dose of CCK. PMID:15235095

Dietary supplementation of branched-chain amino acids increases muscle net amino acid fluxes through elevating their substrate availability and intramuscular catabolism in young pigs.

PubMed

Zheng, Liufeng; Zuo, Fangrui; Zhao, Shengjun; He, Pingli; Wei, Hongkui; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

2017-04-01

Branched-chain amino acids (BCAA) have been clearly demonstrated to have anabolic effects on muscle protein synthesis. However, little is known about their roles in the regulation of net AA fluxes across skeletal muscle in vivo. This study was aimed to investigate the effect and related mechanisms of dietary supplementation of BCAA on muscle net amino acid (AA) fluxes using the hindlimb flux model. In all fourteen 4-week-old barrows were fed reduced-protein diets with or without supplemental BCAA for 28 d. Pigs were implanted with carotid arterial, femoral arterial and venous catheters, and fed once hourly with intraarterial infusion of p-amino hippurate. Arterial and venous plasma and muscle samples were obtained for the measurement of AA, branched-chain α-keto acids (BCKA) and 3-methylhistidine (3-MH). Metabolomes of venous plasma were determined by HPLC-quadrupole time-of-flight-MS. BCAA-supplemented group showed elevated muscle net fluxes of total essential AA, non-essential AA and AA. As for individual AA, muscle net fluxes of each BCAA and their metabolites (alanine, glutamate and glutamine), along with those of histidine, methionine and several functional non-essential AA (glycine, proline and serine), were increased by BCAA supplementation. The elevated muscle net AA fluxes were associated with the increase in arterial and intramuscular concentrations of BCAA and venous metabolites including BCKA and free fatty acids, and were also related to the decrease in the intramuscular concentration of 3-MH. Correlation analysis indicated that muscle net AA fluxes are highly and positively correlated with arterial BCAA concentrations and muscle net BCKA production. In conclusion, supplementing BCAA to reduced-protein diet increases the arterial concentrations and intramuscular catabolism of BCAA, both of which would contribute to an increase of muscle net AA fluxes in young pigs.

The effect on endothelial function of vitamin C during methionine induced hyperhomocysteinaemia.

PubMed

Hanratty, C G; McGrath, L T; McAuley, D F; Young, I S; Johnston, D G

2001-01-01

Manipulation of total homocysteine concentration with oral methionine is associated with impairment of endothelial-dependent vasodilation. This may be caused by increased oxidative stress. Vitamin C is an aqueous phase antioxidant vitamin and free radical scavenger. We hypothesised that if the impairment of endothelial function related to experimental hyperhomocysteinaemia was free radically mediated then co-administration of vitamin C should prevent this. Ten healthy adults took part in this crossover study. Endothelial function was determined by measuring forearm blood flow (FBF) in response to intra-arterial infusion of acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent). Subjects received methionine (100 mg/Kg) plus placebo tablets, methionine plus vitamin C (2 g orally) or placebo drink plus placebo tablets. Study drugs were administered at 9 am on each study date, a minimum of two weeks passed between each study. Homocysteine (tHcy) concentration was determined at baseline and after 4 hours. Endothelial function was determined at 4 hours. Responses to the vasoactive substances are expressed as the area under the curve of change in FBF from baseline. Data are mean plus 95% Confidence Intervals. Following oral methionine tHcy concentration increased significantly versus placebo. At this time endothelial-dependent responses were significantly reduced compared to placebo (31.2 units [22.1-40.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo). Endothelial-independent responses were unchanged. Co-administration of vitamin C did not alter the increase in homocysteine or prevent the impairment of endothelial-dependent responses (31.4 [19.5-43.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo) This study demonstrates that methionine increased tHcy with impairment of the endothelial-dependent vasomotor responses. Administration of vitamin C did not prevent this impairment and our results do not support the hypothesis that the endothelial impairment is mediated by adverse oxidative stress.

Effect of Intrafix® SafeSet infusion apparatus on phlebitis in a neurological intensive care unit: a case-control study.

PubMed

Liu, F; Chen, D; Liao, Y; Diao, L; Liu, Y; Wu, M; Xue, X; You, C; Kang, Y

2012-01-01

To investigate the effect of the Intrafix(®) SafeSet infusion apparatus on the incidence of phlebitis in patients being intravenously infused in a neurological intensive care unit (ICU). Patients aged > 12 years, with no history of diabetes mellitus and no existing phlebitis, requiring a daily peripheral intravenous infusion of ≥ 8 h with the total period lasting ≥ 3 days, were enrolled. Infusions were performed using the Intrafix(®) SafeSet or normal infusion apparatus. Incidence of phlebitis (scored according to the Infusion Nursing Standards of Practice of the American Infusion Nurses Society) was analysed. Patients (n = 1545) were allocated to Intrafix(®) SafeSet (n = 709) or normal infusion (n = 836) groups, matched for age, gender and preliminary diagnosis. Incidence of phlebitis was significantly higher using normal infusion apparatus compared with the Intrafix(®) SafeSet (23.4% versus 17.9%, respectively). Intrafix(®) SafeSet infusion apparatus significantly reduced the incidence of phlebitis in patients in the neurological ICU, compared with normal infusion apparatus, and may be suitable for use in routine clinical practice.

Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

PubMed Central

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

2014-01-01

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

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.

Regular aerobic exercise reduces endothelin-1-mediated vasoconstrictor tone in overweight and obese adults.

PubMed

Dow, Caitlin A; Stauffer, Brian L; Brunjes, Danielle L; Greiner, Jared J; DeSouza, Christopher A

2017-09-01

What is the central question of this study? Does aerobic exercise training reduce endothelin-1 (ET-1)-mediated vasoconstrictor tone in overweight/obese adults? And, if so, does lower ET-1 vasoconstriction underlie the exercise-related enhancement in endothelium-dependent vasodilatation in overweight/obese adults? What is the main finding and its importance? Regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight/obese adults, independent of weight loss. Decreased ET-1 vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults. Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in overweight and obese adults, contributing to vasomotor dysfunction and increased cardiovascular disease risk. Although the effects of habitual aerobic exercise on endothelium-dependent vasodilatation in overweight/obese adults have been studied, little is known regarding ET-1-mediated vasoconstriction. Accordingly, the aims of the present study were to determine the following: (i) whether regular aerobic exercise training reduces ET-1-mediated vasoconstrictor tone in overweight and obese adults; and, if so, (ii) whether the reduction in ET-1-mediated vasoconstriction contributes to exercise-induced improvement in endothelium-dependent vasodilatation in this population. Forearm blood flow (FBF) in response to intra-arterial infusion of selective ET A receptor blockade (BQ-123, 100 nmol min -1 for 60 min), acetylcholine [4.0, 8.0 and 16.0 μg (100 ml tissue) -1  min -1 ] in the absence and presence of ET A receptor blockade and sodium nitroprusside [1.0, 2.0 and 4.0 μg (100 ml tissue) -1  min -1 ] were determined before and after a 3 month aerobic exercise training intervention in 25 (16 men and nine women) overweight/obese (body mass index 30.1 ± 0.5 kg m -2 ) adults. The vasodilator response to BQ-123 was significantly lower (∼25%) and the FBF responses to acetylcholine were ∼35% higher after exercise training. Before the exercise intervention, the co-infusion of acetylcholine plus BQ-123 resulted in a greater vasodilator response than acetylcholine alone; however, after the exercise intervention the FBF response to acetylcholine was not significantly increased by ET A receptor blockade. These results demonstrate that regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight and obese adults. Moreover, decreased ET-1-mediated vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

[Morphine self-administration by rats using a pneumatic syringe].

PubMed

Akiyama, Y; Takayama, S

1988-06-01

An apparatus for drug self-administration by rats using a pneumatic syringe was developed by Weeks. A microliter syringe operated by a pneumatic cylinder supplies an accurate volume of drug solution within one second. When coefficient of variation of infusion volume was compared among pneumatic syringe, infusion pump, and peristaltic pump, pneumatic syringe showed higher accuracy in infusion volume than the other two pumps. Since the infusion speed by a pneumatic syringe is very rapid (less than one second per infusion), the effect of infusion speed on reinforcing property of morphine was investigated. When rats self-administered 0.1, 0.3, 1.0, and 3.0 mg/kg/infusion of morphine by pneumatic syringes, the patterns of self-infusion were more stable, the number of self-infusions and the amount self-administered were larger, and a dose-response relationship was clearer in comparison with those self-infused the same doses of morphine for 5.6 seconds by infusion pumps or peristaltic pumps.

Comparison of 20-, 23-, and 25-gauge air infusion forces.

PubMed

Machado, Leonardo Martins; Magalhães, Octaviano; Maia, Mauricio; Rodrigues, Eduardo B; Farah, Michel Eid; Ismail, Kamal A R; Molon, Leandro; Oliveira, Danilo A

2011-11-01

To determine and compare 20-, 23-, and 25-gauge retinal infusion air jet impact pressure (force per unit area) in an experimental setting. Experimental laboratory investigation. Infusion cannulas were connected to a compressed air system. A controlled valve mechanism was used to obtain increasing levels of infusion pressure. Each infusion tube was positioned in front of a manual transducer to measure force. Impact pressure was calculated using known formulas in fluid dynamics. The 20-gauge infusion jet showed similar impact pressure values compared with the 23-gauge infusion jet. Both showed higher levels than the 25-gauge infusion jet. This was because of the smaller jet force for the 25-gauge system. In this experimental study, both the 23- and the 20-gauge air infusion jet showed higher impact pressure values compared with the 25-gauge air infusion jet. This could be of concern regarding air infusion during 23-gauge vitrectomy since retinal damage has been shown in standard-gauge surgeries.

Infusion volume control and calculation using metronome and drop counter based intravenous infusion therapy helper.

PubMed

Park, Kyungnam; Lee, Jangyoung; Kim, Soo-Young; Kim, Jinwoo; Kim, Insoo; Choi, Seung Pill; Jeong, Sikyung; Hong, Sungyoup

2013-06-01

This study assessed the method of fluid infusion control using an IntraVenous Infusion Controller (IVIC). Four methods of infusion control (dial flow controller, IV set without correction, IV set with correction and IVIC correction) were used to measure the volume of each technique at two infusion rates. The infused fluid volume with a dial flow controller was significantly larger than other methods. The infused fluid volume was significantly smaller with an IV set without correction over time. Regarding the concordance correlation coefficient (CCC) of infused fluid volume in relation to a target volume, IVIC correction was shown to have the highest level of agreement. The flow rate measured in check mode showed a good agreement with the volume of collected fluid after passing through the IV system. Thus, an IVIC could assist in providing an accurate infusion control. © 2013 Wiley Publishing Asia Pty Ltd.

Intravenous Ketamine Infusions for Neuropathic Pain Management: A Promising Therapy in Need of Optimization.

PubMed

Maher, Dermot P; Chen, Lucy; Mao, Jianren

2017-02-01

Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes. Increased duration of relief from neuropathic pain is associated with (1) higher total infused doses of ketamine; (2) prolonged infusion durations, although the rate of infusion does not appear to be a factor; and (3) coadministration of adjunct medications such as midazolam and/or clonidine that mitigate some of the unpleasant psychomimetic side effects. However, there are few studies designed to optimize ketamine infusion protocols by defining what an effective infusion protocol entails with regard to a respective neuropathic pain condition. Therefore, despite common clinical practice, the current state of the literature leaves the use of ketamine infusions without meaningful guidance from high-quality comparative evidence. The objectives of this topical review are to (1) analyze the available clinical evidence related to ketamine infusion protocols and (2) call for clinical studies to identify optimal ketamine infusion protocols tailored for individual neuropathic pain conditions. The Oxford Center for Evidence-Based Medicine classification for levels of evidence was used to stratify the grades of clinical recommendation for each infusion variable studied.

Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function.

PubMed

Lukyanenko, Yevgeniya O; Younes, Antoine; Lyashkov, Alexey E; Tarasov, Kirill V; Riordon, Daniel R; Lee, Joonho; Sirenko, Syevda G; Kobrinsky, Evgeny; Ziman, Bruce; Tarasova, Yelena S; Juhaszova, Magdalena; Sollott, Steven J; Graham, David R; Lakatta, Edward G

2016-09-01

Constitutive Ca(2+)/calmodulin (CaM)-activation of adenylyl cyclases (ACs) types 1 and 8 in sinoatrial nodal cells (SANC) generates cAMP within lipid-raft-rich microdomains to initiate cAMP-protein kinase A (PKA) signaling, that regulates basal state rhythmic action potential firing of these cells. Mounting evidence in other cell types points to a balance between Ca(2+)-activated counteracting enzymes, ACs and phosphodiesterases (PDEs) within these cells. We hypothesized that the expression and activity of Ca(2+)/CaM-activated PDE Type 1A is higher in SANC than in other cardiac cell types. We found that PDE1A protein expression was 5-fold higher in sinoatrial nodal tissue than in left ventricle, and its mRNA expression was 12-fold greater in the corresponding isolated cells. PDE1 activity (nimodipine-sensitive) accounted for 39% of the total PDE activity in SANC lysates, compared to only 4% in left ventricular cardiomyocytes (LVC). Additionally, total PDE activity in SANC lysates was lowest (10%) in lipid-raft-rich and highest (76%) in lipid-raft-poor fractions (equilibrium sedimentation on a sucrose density gradient). In intact cells PDE1A immunolabeling was not localized to the cell surface membrane (structured illumination microscopy imaging), but located approximately within about 150nm inside of immunolabeling of hyperpolarization-activated cyclic nucleotide-gated potassium channels (HCN4), which reside within lipid-raft-rich microenvironments. In permeabilized SANC, in which surface membrane ion channels are not functional, nimodipine increased spontaneous SR Ca(2+) cycling. PDE1A mRNA silencing in HL-1 cells increased the spontaneous beating rate, reduced the cAMP, and increased cGMP levels in response to IBMX, a broad spectrum PDE inhibitor (detected via fluorescence resonance energy transfer microscopy). We conclude that signaling via cAMP generated by Ca(2+)/CaM-activated AC in SANC lipid raft domains is limited by cAMP degradation by Ca(2+)/CaM-activated PDE1A in non-lipid raft domains. This suggests that local gradients of [Ca(2+)]-CaM or different AC and PDE1A affinity regulate both cAMP production and its degradation, and this balance determines the intensity of Ca(2+)-AC-cAMP-PKA signaling that drives SANC pacemaker function. Copyright © 2016. Published by Elsevier Ltd.

Reversal of behavioral depression by infusion of an alpha-2 adrenergic agonist into the locus coeruleus.

PubMed

Simson, P G; Weiss, J M; Hoffman, L J; Ambrose, M J

1986-04-01

This experiment demonstrated that behavioral depression produced by exposure of rats to strong uncontrollable shocks could be reversed by infusion of the alpha-2 adrenergic agonist clonidine into the region of the locus coeruleus (LC). A 20-min infusion, through bilateral cannulae, into the locus coeruleus of clonidine, piperoxane (alpha-2 antagonist) or inactive vehicle (0.85% saline), was given beginning 70 min after the animals were removed from the stress situation. The dose and volume of drug given in the infusion (0.16 microgram/microliter, 0.1 microliter/min) had been previously shown to produce effects specific to the locus coeruleus (Weiss, Simson, Hoffman, Ambrose, Cooper and Webster, 1986; Neuropharmacology 25: 367-384). At the conclusion of the infusion, active behavior of animals was measured in a 15-min swim test. Results showed that stressed animals infused with vehicle exhibited significantly less active behavior in the swim test than did non-stressed animals infused with vehicle, thereby showing the usual behavioral depression seen after exposure to an uncontrollable stress. Stressed animals infused with clonidine showed no difference in active behavior in comparison to non-stressed animals infused with vehicle and showed significantly more activity than did the stressed animals infused with vehicle. Stressed animals infused with piperoxane showed no significant difference in activity in comparison to the stressed animals infused with vehicle and were significantly less active than either the non-stressed animals infused with vehicle or the stressed animals infused with clonidine. Thus, infusion into the locus coeruleus of the alpha-2 agonist clonidine, but not the alpha-2 antagonist piperoxane, eliminated behavioral depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Rethinking the Role of Nitroglycerin Ointment in Ischemic Vascular Filler Complications: An Animal Model With ICG Imaging.

PubMed

Hwang, Catherine J; Morgan, Payam V; Pimentel, Aline; Sayre, James W; Goldberg, Robert A; Duckwiler, Gary

2016-01-01

Soft tissue dermal fillers, both temporary and permanent, are used frequently in facial rejuvenation. As the use of fillers increases, ischemic complications including skin necrosis are becoming more prevalent. In the literature, topical nitroglycerin paste has been recommended in the early treatment of patients presenting with ischemia. The purpose of this study was to evaluate the vascular perfusion effects of topical nitroglycerin paste in an animal model using indocyanine green (ICG) imaging. After Animal Research Committee approval, a rabbit ear model was used to create filler-associated skin ischemia. Ischemia was confirmed to occur after intra-arterial occlusion. Four commonly used soft tissue fillers were injected intra-arterially: Radiesse (Merz USA, Greensboro NC), Restylane (Galderma, Ft. Worth, TX), Juvederm Ultra (Allergan, Irvine CA), Belotero (Merz USA, Greensboro NC) (0.1 ml). A total of 15 ears were used, 1 control and 4 experimental per product. Thirty minutes after occlusion, nitroglycerin ointment USP, 2%(Nitro-Bid) was applied topically to the experimental ears. Vascular perfusion was evaluated with the SPY System (Novadaq Inc.) using ICG imaging. Perfusion images were obtained at baseline, immediately after, and 30 minutes after intra-arterial filler injection, and at 30, 60, 90, and 120 minutes after application of topical nitroglycerin ointment. In this rabbit ear model, no statistically significant improvement in perfusion was noted after topical application of nitroglycerin paste with ICG imaging. In addition, the skin of the rabbit ear post-nitroglycerin ointment appeared to have more of a congested appearance than the controls. Ischemic filler complications are becoming increasingly prevalent. Practitioners often treat these complications with topical nitroglycerin paste based on the knowledge that topical nitroglycerin causes vasodilation. In filler-induced tissue ischemia, however, filler product is present within arterioles. Theoretically, applying nitroglycerin paste, at least early, may not improve perfusion and could worsen ischemia with dilation of vessels and further propagation of product into the smaller arterioles and capillaries. In addition, nitroglycerin paste has systemic effects, including hypotension and dizziness, which may not be tolerated by some patients. Therefore, the authors caution the use of topical nitroglycerin paste in patients presenting with filler-associated ischemia. Further studies in the best treatment algorithms for patients presenting with ischemic complications need to be performed.

Intra-arterial therapies for unresectable and chemorefractory colorectal cancer liver metastases: a systematic review and meta-analysis.

PubMed

Levy, Jordan; Zuckerman, Jesse; Garfinkle, Richard; Acuna, Sergio A; Touchette, Jacynthe; Vanounou, Tsafrir; Pelletier, Jean-Sebastien

2018-06-07

A large proportion of patients with colorectal cancer liver metastases (CRCLM) not amenable to curative liver resection will progress on systemic therapy. Intra-arterial therapies (IAT) including conventional transarterial chemoembolization (cTACE), drug eluting beads (DEB-TACE) and yttrium-90 radioembolization (Y-90) are indicated to prolong survival and palliate symptoms. The purpose of this systematic review and meta-analysis is to compare the survival benefit and radiologic response of three intra-arterial therapies in patients with chemorefractory and unresectable CRCLM. A systematic search for eligible references in the Cochrane Library and the EMBASE, MEDLINE and TRIP databases from January 2000 to November 2016 was performed in accordance with PRISMA guidelines. Methodological quality of included studies was assessed using the MINORS scale. One-year overall survival rates and RECIST responder rates were pooled using inverse-variance weighted random-effects models. Overall survival outcomes were collected according to transformed pooled median survivals from first IAT with a subgroup analysis of patients with extrahepatic disease. Twenty-three prospective studies were included and analyzed: 5 cTACE (n = 746), 5 DEB-TACE (n = 222) and 13 Y-90 (n = 615). All but five were clinical trials. Eleven of 13 Y-90 studies were industry funded. Pooled RECIST response rates with 95% confidence intervals (CI) were: cTACE 23% (9.7, 36), DEB-TACE 36% (0, 73) and Y-90 23% (11, 34). The pooled 1-year survival rates with CI were: cTACE, 70% (49, 87), DEB-TACE, 80% (74, 86) and Y-90, 41% (28, 54). Transformed pooled median survivals from first IAT and ranges for cTACE, DEB-TACE and Y-90 were 16 months (9.0-23), 16 months (7.3-25) and 12 months (7.0-15), respectively. Significant heterogeneity in inclusion criteria and reporting of confounders, including previous therapy, tumor burden and post-IAT therapy, precluded statistical comparisons between the three therapies. Methodological and statistical heterogeneity precluded consensus on the optimal treatment strategy. Given the common use and significant cost of radioembolization in this setting, a more robust prospective comparative trial is warranted. Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous infusions of large volumes of immunoglobulin in a swine model.

PubMed

Kang, David W; Jadin, Laurence; Nekoroski, Tara; Drake, Fred H; Zepeda, Monica L

2012-08-01

Many patients with primary immunodeficiency disease (PIDD) require lifelong immunoglobulin (Ig) replacement therapy. Home-based subcutaneous (SC) infusion provides advantages to patients with PIDD compared to hospital-based intravenous infusion. One limitation of current practice with SCIg infusion is the need for small-volume infusions at multiple injection sites on a frequent basis. A method was developed for large-volume SC infusion that uses preinfusion of recombinant human hyaluronidase (rHuPH20) to facilitate fluid dispersion. Miniature swine was used as a preclinical model to assess the effects of rHuPH20-facilitated infusions, of a single monthly dose, on fluid dispersion, infusion-related pressure, swelling, induration, and tissue damage. Preinfusion of vehicle (control) or rHuPH20 (75 U/g Ig) was performed simultaneously on contralateral abdominal sites on each animal, followed by infusion of 300 mL 10 % Ig (30 g) at each site. Compared to control infusions, rHuPH20 significantly reduced infusion pressure and induration (p < 0.05) and accelerated postinfusion Ig dispersion. Histological evaluation of infusion site tissue showed moderate to severe swelling for the control. Swelling after rHuPH20-facilitated infusion was mild on day 1 and had completely resolved shortly thereafter. Laser Doppler imaging of control infusion sites revealed local cutaneous hypoperfusion during Ig infusion, which was reduced almost 7-fold (p < 0.05) with the use of rHuPH20. These results demonstrate that rHuPH20-facilitated Ig infusion is associated with improved dispersion of Ig, resulting in reduced tissue pressure, induration, and reduced risk of tissue damage from mechanical trauma or local ischemia, thus enabling SC administration of large volumes of Ig at a single site.

The influence of gastrointestinal infusion of fats on regulation of food intake in pigs.

PubMed Central

Gregory, P C; Rayner, D V

1987-01-01

1. The influence of gastrointestinal infusions of fat on short-term and 24 h control of food intake were studied in twenty-four pigs fed twice per day and seventeen fed three times per day. The pigs were fitted with up to four catheters placed in the stomach, the duodenum, and at 2, 4 and 8 m from the ligament of Treitz. 2. Various infusions were given into the catheters beginning 30 min before the first meal (two feeds) or second meal (three feeds) of the day and continuing until the end of the feeding period or until the pigs stopped eating. 3. Infusions of a fat emulsion (Intralipid) into the stomach, of oleic acid or glycerol into the duodenum, or of glycerol into the ileum (8 m from the ligament of Treitz) inhibited food intake during the infusion according to the amount of energy infused. 4. Food intake was inhibited by more than the amount of energy infused with duodenal infusion of Intralipid or monoglyceride, or with infusion of Intralipid mixed with bile salts and lipase (but not with Intralipid alone) into 2 or 4 m from the ligament of Treitz. 5. Duodenal infusion of glycerol, and ileal (8 m from the ligament of Treitz) infusion of monoglyceride or glycerol inhibited food intake at the following meal according to the amount of energy infused. 6. It is concluded that fats can exert both pre- and post-absorptive control of food intake and that since Intralipid infusion to the stomach but not to the duodenum inhibits food intake according to the amount of energy infused, it is likely that control of food intake is related to control of stomach emptying. 7. The inhibition of food intake by more than the amount of energy infused during upper intestinal infusion of fat is likely to be a result of digestion of the fat to monoglycerides, and interaction of monoglycerides with receptors in the proximal 4 m of intestine. PMID:3656166

Effect of Prophylactic Extended-Infusion Carboplatin on Incidence of Hypersensitivity Reactions in Patients with Ovarian, Fallopian Tube, or Peritoneal Carcinomas.

PubMed

Pasternak, Amy L; Link, Nicholas A; Richardson, Carolyn M; Rose, Peter G

2016-07-01

To determine whether extended-infusion carboplatin, initiated at approximately the eighth cumulative carboplatin cycle and prior to development of carboplatin hypersensitivity, reduces the incidence of carboplatin hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal cancer. Retrospective chart review. Large integrated health system. A total of 326 patients with ovarian, fallopian tube, or primary peritoneal cancer who received at least eight cumulative cycles of carboplatin between January 2007 and September 2014 were included. Of these, 161 patients received all doses of carboplatin infused over 30 or 60 minutes (standard-infusion group [total of 1317 carboplatin cycles]), and 165 patients received the 3-hour extended infusion of carboplatin administered at approximately the eighth cumulative cycle and prior to development of a hypersensitivity reaction (extended-infusion group [total of 1527 carboplatin cycles]). Baseline characteristics were similar between the groups, except significantly more patients in the extended-infusion group received triple premedication therapy prior to infusion (p<0.001). Hypersensitivity reactions occurred in 64 patients (40%) who received standard-infusion carboplatin and 40 patients (24.2%) who received extended-infusion carboplatin (p=0.0027). The median cycle of hypersensitivity reaction development did not differ significantly between the groups: 9 cycles in patients who received standard-infusion versus 11 cycles in patients who received extended-infusion carboplatin (p=0.06). Through regression analysis, the premedication regimen received prior to carboplatin infusion was the only variable significantly associated with hypersensitivity reactions (odds ratio 0.59, 95% confidence interval 0.36-0.97, p=0.038). Patients who received extended-infusion carboplatin experienced a lower incidence of hypersensitivity reactions than patients who received standard-infusion carboplatin, which may be attributed to the triple premedication regimen received more frequently in patients in the extended-infusion group. © 2016 Pharmacotherapy Publications, Inc.

Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain.

PubMed

Moulin, D E; Kreeft, J H; Murray-Parsons, N; Bouquillon, A I

1991-02-23

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.

Cell Saver for Adult Spinal Deformity Surgery Reduces Cost.

PubMed

Gum, Jeffrey L; Carreon, Leah Yacat; Kelly, Michael P; Hostin, Richard; Robinson, Chessie; Burton, Douglas C; Polly, David W; Shaffrey, Christopher I; LaFage, Virginie; Schwab, Frank J; Ames, Christopher P; Kim, Han Jo; Smith, Justin S; Bess, R Shay

2017-07-01

Retrospective cohort. To determine if the use of cell saver reduces overall blood costs in adult spinal deformity (ASD) surgery. Recent studies have questioned the clinical value of cell saver during spine procedures. ASD patients enrolled in a prospective, multicenter surgical database who had complete preoperative and surgical data were identified. Patients were stratified into (1) cell saver available during surgery, but no intraoperative autologous infusion (No Infusion group), or (2) cell saver available and received autologous infusion (Infusion group). There were 427 patients in the Infusion group and 153 in the No infusion group. Patients in both groups had similar demographics. Mean autologous infusion volume was 698 mL. The Infusion group had a higher percentage of EBL relative to the estimated blood volume (42.2%) than the No Infusion group (19.6%, p < .000). Allogeneic transfusion was more common in the Infusion group (255/427, 60%) than the No Infusion group (67/153, 44%, p = .001). The number of allogeneic blood units transfused was also higher in the Infusion group (2.4) than the No Infusion group (1.7, p = .009). Total blood costs ranged from $396 to $2,146 in the No Infusion group and from $1,262 to $5,088 in the Infusion group. If the cost of cell saver blood was transformed into costs of allogeneic blood, total blood costs for the Infusion group would range from $840 to $5,418. Thus, cell saver use yielded a mean cost savings ranging from $330 to $422 (allogeneic blood averted). Linear regression showed that after an EBL of 614 mL, cell saver becomes cost-efficient. Compared to transfusing allogeneic blood, cell saver autologous infusion did not reduce the proportion or the volume of allogeneic transfusion for patients undergoing surgery for adult spinal deformity. The use of cell saver becomes cost-efficient above an EBL of 614 mL, producing a cost savings of $330 to $422. Level III. Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Accidental intra-arterial injection of fluorescein dye.

PubMed

Bovino, J A; Marcus, D F

1984-12-01

During fluorescein angiography, sodium fluorescein dye intended for intravenous use was inadvertently injected into an artery in the antecubital fossa. An immediate and dramatic orange discoloration of the skin distal to the injection combined with intense burning pain of the right forearm and hand were noted. The patient was treated with ice packs and analgesics. The fluorescein angiogram showed a delayed arm to eye circulation time, but was of normal quality. There were no long-term complications.

Hospital-acquired gangrenous mucormycosis.

PubMed Central

Patterson, J. E.; Barden, G. E.; Bia, F. J.

1986-01-01

A post-operative diabetic patient who had been treated for Serratia marcescens bacterial sepsis developed recurrent thrombosis of the left femoral artery following intra-arterial instrumentation. Pathological examination of arterial thrombus ultimately demonstrated invasive mucormycosis of the femoral artery and cultures of this material grew Rhizopus oryzae. The occurrence of cutaneous and subcutaneous mucormycosis is reviewed, as well as recently recognized nosocomial risk factors for mucormycosis, such as elasticized bandages and wound dressings. Images FIG. 1 FIG. 2 FIG. 3 PMID:3765666

Revisiting intra-arterial drug delivery for treating brain diseases or is it "déjà-vu, all over again"?

PubMed

Joshi, Shailendra; Ellis, Jason A; Emala, Charles W

2014-05-01

For over six decades intra-arterial (IA) drugs have been sporadically used for the treatment of lethal brain diseases. In recent years considerable advance has been made in the IA treatment of retinoblastomas, liver and locally invasive breast cancers, but relatively little progress has been made in the treatment of brain cancers. High resting blood flow and the presence of the blood-brain barrier (BBB), makes IA delivery to the brain tissue far more challenging, compared to other organs. The lack of advance in the field is also partly due to the inability to understand the complex pharmacokinetics of IA drugs as it is difficult to track drug concentrations in sub-second time frame by conventional chemical methods. The advances in optical imaging now provide unprecedented insights into the pharmacokinetics of IA drug and optical tracer delivery. Novel delivery methods, improved IA drug formulations, and optical pharmacokinetics, present us with untested paradigms in pharmacology that could lead to new therapeutic interventions for brain cancers and stroke. The object of this review is to bring into focus the current practice, problems, and the potential of IA drug delivery for treating brain diseases. A concerted effort is needed at basic sciences (pharmacology and drug imaging), and translational (drug delivery techniques and protocol development) levels by the interventional neuroradiology community to advance the field.

Predictive Factors of Downstaging of Hepatocellular Carcinoma Beyond the Milan Criteria Treated with Intra-arterial Therapies

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

Bova, Valentina; Miraglia, Roberto, E-mail: rmiraglia@ismett.edu; Maruzzelli, Luigi

2013-04-15

This study was designed to analyze the clinical results in patients suitable for liver transplantation with hepatocellular carcinoma (HCC) who exceeded Milan criteria, which underwent intra-arterial therapies (IAT), to determine predictive factors of successful downstaging. A total of 277 consecutive patients with cirrhosis and HCC were treated by IAT (transarterial oily chemoembolization, transarterial chemoembolization, transarterial embolization) in a single center. Eighty patients exceed the Milan criteria. Patients with infiltrative HCC, hypovascular HCC, and portal vein thrombosis were excluded, with a final study population of 48 patients. Tumor response to IAT was evaluated with CT and/or MRI according to modified RECISTmore » criteria. Successful downstaging was defined as a reduction in the number and size of viable tumors to within the Milan criteria, and serum alpha-fetoprotein (AFP) <100 ng/mL, for at least 6 months. Nineteen patients (39 %) had their tumors successfully downstaged; 29 patients (61 %) did not. Multivariate analysis showed that AFP level <100 ng/mL and 3-year calculated survival probability using the Metroticket calculator were the only independent predictors of successful downstaging (p < 0.023 and p < 0.049 respectively). Biological characteristics of HCC as AFP levels <100 ng/mL and high 3-year calculated survival probability may predict a good response to downstage after IAT.« less

Extended versus Bolus Infusion of Broad Spectrum β-Lactams for Febrile Neutropenia: an Unblinded Randomized Trial.

PubMed

Ram, Ron; Halavy, Yael; Amit, Odelia; Paran, Yael; Katchman, Eugene; Yachini, Bruria; Kor, Svetlana; Avivi, Irit; Ben-Ami, Ronen

2018-03-28

Febrile neutropenia may be a sign of severe infection, and is associated with significant morbidity and mortality in high-risk patients with hematologic malignancies. Extended infusion of β-lactam antibiotics is associated with greater clinical response than is bolus infusion in non-neutropenic critically ill patients, but data are lacking for febrile neutropenic patients. We designed a single-center, non-blinded randomized trial comparing extended infusion (4 hours) and bolus infusion (30 minutes) of piperacillin-tazobactam or ceftazidime in high-risk patients with febrile neutropenia. The primary end-point was overall response on day 4, defined as the combination of resolution of fever, sterile blood cultures, resolution of clinical signs and symptoms, and no need for a change in the antibiotic regimen. Outcome was adjudicated by investigators blinded to treatment allocation. Of 123 enrolled patients, 105 had febrile neutropenia and were included in the intention-to-treat analysis: 47 in the extended infusion arm and 58 in the bolus infusion arm. Overall response occurred in 35 (74.4%) patients treated with extended infusion and 32 (55.1%) patients treated with bolus infusion (P=0.044). The superiority of extended infusion compared with bolus infusion was greatest for patients with clinically documented infections (overall response, 68.4% [13/19] versus 35.7% [10/28]; P=0.039), and specifically for those with pneumonia (80% [4/5] versus 0% [0/8]; P=0.007). Extended infusion of β-lactams is associated with superior treatment outcomes as compared with bolus infusion for high-risk patients with febrile neutropenia. The benefit of extended β-lactam infusion may be greatest for patients with pulmonary infections.

Infusion pressure and pain during microneedle injection into skin of human subjects.

PubMed

Gupta, Jyoti; Park, Sohyun S; Bondy, Brian; Felner, Eric I; Prausnitz, Mark R

2011-10-01

Infusion into skin using hollow microneedles offers an attractive alternative to hypodermic needle injections. However, the fluid mechanics and pain associated with injection into skin using a microneedle have not been studied in detail before. Here, we report on the effect of microneedle insertion depth into skin, partial needle retraction, fluid infusion flow rate and the co-administration of hyaluronidase on infusion pressure during microneedle-based saline infusion, as well as on associated pain in human subjects. Infusion of up to a few hundred microliters of fluid required pressures of a few hundred mmHg, caused little to no pain, and showed weak dependence on infusion parameters. Infusion of larger volumes up to 1 mL required pressures up to a few thousand mmHg, but still usually caused little pain. In general, injection of larger volumes of fluid required larger pressures and application of larger pressures caused more pain, although other experimental parameters also played a significant role. Among the intradermal microneedle groups, microneedle length had little effect; microneedle retraction lowered infusion pressure but increased pain; lower flow rate reduced infusion pressure and kept pain low; and use of hyaluronidase also lowered infusion pressure and kept pain low. We conclude that microneedles offer a simple method to infuse fluid into the skin that can be carried out with little to no pain. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Effect of hyperosmotic solutions on salt excretion and thirst in rats

NASA Technical Reports Server (NTRS)

Schoorlemmer, G. H.; Johnson, A. K.; Thunhorst, R. L.

2000-01-01

We investigated urinary changes and thirst induced by infusion of hyperosmotic solutions in freely moving rats. Intracarotid infusions of 0.3 M NaCl (4 ml/20 min, split between both internal carotid arteries) caused a larger increase in excretion of Na(+) and K(+) than intravenous infusions, indicating that cephalic sensors were involved in the response to intracarotid infusions. Intravenous and intracarotid infusions of hyperosmotic glycerol or urea (300 mM in 150 mM NaCl) had little or no effect, suggesting the sensors were outside the blood-brain barrier (BBB). Intracarotid infusion of hypertonic mannitol (300 mM in 150 mM NaCl) was more effective than intravenous infusion, suggesting that cell volume rather than Na(+) concentration of the blood was critical. Similarly, intracarotid infusion (2 ml/20 min, split between both sides), but not intravenous infusion of hypertonic NaCl or mannitol caused thirst. Hyperosmotic glycerol, infused intravenously or into the carotid arteries, did not cause thirst. We conclude that both thirst and electrolyte excretion depend on a cell volume sensor that is located in the head, but outside the BBB.

Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats

PubMed Central

Hales, Jena B.; Ocampo, Amber C.; Broadbent, Nicola J.; Clark, Robert E.

2015-01-01

Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion. PMID:26380123

Minimum infusion rate and adrenocortical function after continuous infusion of the novel etomidate analog ET-26-HCl in rats.

PubMed

Jiang, Junli; Wang, Bin; Zhu, Zhaoqiong; Yang, Jun; Liu, Jin; Zhang, Wensheng

2017-01-01

Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia. The up-and-down method was used to determine the minimum infusion rates for ET-26-HCl, etomidate and CPMM. Sprague-Dawley rats ( n  = 32) were then randomly divided into four groups: etomidate, ET-26-HCl, CPMM, and vehicle control. Rats in each group were infused for 60 min with one of the drugs at its predetermined minimum infusion rate. Blood samples were drawn initially and then every 30 min after drug infusion to determine the adrenocorticotropic hormone-stimulated concentration of serum corticosterone as a measure of adrenocortical function. The minimum infusion rates for etomidate, ET-26-HCl and CPMM were 0.29, 0.62, and 0.95 mg/kg/min, respectively. Compared with controls, etomidate decreased serum corticosterone, as expected, whereas serum corticosterone concentrations following infusion with the etomidate analogs ET-26-HCl or CPMM were not significantly different from those in the control group. The corticosterone concentrations tended to be reduced for the first hour following ET-26-HCl infusion (as compared to vehicle infusion); however, this reduction did not reach statistical significance. Thus, further studies are warranted examining the practicability of using ET-26-HCl as an infused anesthetic.

[How to promote the respect of good infusion practices by meeting health care professionals?].

PubMed

Le Reste, C; Fiedler, A; Dubois, S; Dewailly, A; Le Du, I; Cogulet, V

2016-05-01

Health care professionals often forget that there are risks associated with infusion therapy even if it is a common care. In order to assess this practice and to draw potential improvement actions, an audit of local gravity-flow intravenous infusion practices was conducted. The audit, based on a grid including 66 items from the medical prescription to the end of the infusion therapy administration, was conducted in the 6 units which use the most gravity-flow intravenous infusion devices. A multidisciplinary working group was created to decide and organize priority corrective measures in order to improve infusion practices and quality of healthcare. The audit enabled to observe 90hours of nurse's practices (96 infusions) and highlighted heterogeneity in infusion, in some cases inappropriate infusion practices and misuse of infusion devices. We found 4 main issues: labelling infusion therapy, training of health care professionals on good practices, support the purchase of infusion pumps and standardize perfusion line. An interactive educational program for nurses (workshops) was organized to enhance the respect of good practices: infusion identification at any time, respect of hygiene rules, flow rate regulation by counting drops, appropriate use of pumps and flow rate regulators. The audit drew up work priorities. The workshops made easier exchanges between professionals and had a warm welcome that's why it is essential to carry on such training. This collaborative approach between pharmacists, nurses, hygienists and biomedical technicians contribute to drug management improvement and promote optimal patient care. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

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.

Methods of preventing vinorelbine-induced phlebitis: an experimental study in rabbits.

PubMed

Kohno, Emiko; Murase, Saori; Nishikata, Mayumi; Okamura, Noboru; Matzno, Sumio; Kuwahara, Takashi; Matsuyama, Kenji

2008-07-22

In order to identify methods for preventing phlebitis caused by intravenous administration of vinorelbine (VNR), we established a procedure for estimating the severity of phlebitis in an animal model. Four different factors (administration rate, dilution, flushing, and infusion of fat emulsion) were evaluated for alleviation of phlebitis caused by VNR infusion. VNR was diluted with normal saline to prepare test solutions with concentrations of 0.6 mg/mL or 0.3 mg/mL for infusion into the auricular veins of rabbits. Two days after VNR infusion, the veins were subjected to histopathological examination. VNR did not cause obvious loss of venous endothelial cells, the most sensitive and common feature of phlebitis, but VNR infusion led to inflammatory cell infiltration, edema, and epidermal degeneration. Tissue damage was significantly decreased by shortening the administration time and by diluting the VNR solution for infusion from 0.6 mg/mL to 0.3 mg/mL. However, there was no effect of flushing with normal saline after VNR infusion, while treatment with fat emulsion before and after VNR infusion only had a minimal effect. Rapid infusion and dilution are effective methods of reducing phlebitis caused by the infusion of VNR, but the efficacy of flushing with normal saline or infusion of fat emulsion was not confirmed.

Accelerated infliximab infusions for inflammatory bowel disease improve effectiveness.

PubMed

McConnell, John; Parvulescu-Codrea, Simona; Behm, Brian; Hill, Beth; Dunkle, Elizabeth; Finke, Karen; Snyder, Kathryn; Tuskey, Anne; Cox, Debbie; Woodward, Beth

2012-10-06

To study the safety and effectiveness associated with accelerated infliximab infusion protocols in patients with inflammatory bowel disease (IBD). Original protocols and infusion rates were developed for the administration of infliximab over 90-min and 60-min. Then the IBD patients on stable maintenance infliximab therapy were offered accelerated infusions. To be eligible for the study, patients needed a minimum of four prior infusions. An initial infusion of 90-min was given to each patient; those tolerating the accelerated infusion were transitioned to a 60-min infusion protocol at their next and all subsequent visits. Any patient having significant infusion reactions would be reverted to the standard 120-min protocol. A change in a patient's dose mandated a single 120-min infusion before accelerated infusions could be administered again. The University of Virginia Medical Center's Institutional Review Board approved this study. Fifty IBD patients treated with infliximab 5 mg/kg, 7.5 mg/kg and 10 mg/kg were offered accelerated infusions. Forty-six patients consented to participate in the study. Nineteen (41.3%) were female, five (10.9%) were African American and nine (19.6%) had ulcerative colitis. The mean age was 42.6 years old. Patients under age 18 were excluded. Ten patients used immunosuppressive drugs concurrently out of which six were taking azathioprine, three were taking 6-mercaptopurine and one was taking methotrexate. One of the 46 study patients used corticosteroid therapy for his IBD. Seventeen of the patients used prophylactic medications prior to receiving infusions; six patients received corticosteroids as pre-medication. Four patients had a history of distant transfusion reactions to infliximab. These reactions included shortness of breath, chest tightness, flushing, pruritus and urticaria. These patients all took prophylactic medications before receiving infusions. 46 patients (27 males and 19 females) received a total of fifty 90-min infusions and ninety-three 60-min infusions. No infusion reactions were reported. There were no adverse events, including drug-related infections. None of the patients developed cancer of any type during the study timeframe. Total cost savings for administration of the both 90-min and 60-min accelerated infusions compared to standard 120-min infusions was estimated to be $53 632 ($116 965 vs $63 333, P = 0.001). One hundred and eighteen hours were saved in the administration of the accelerated infusions (17 160 min vs 10 080 min, P = 0.001). In the study population, overweight females [body mass index (BMI) > 25.00 kg/m(2)] were found to have statistically higher BMIs than overweight males (mean BMI 35.07 ± 2.66 kg/m(2) vs 30.08 ± 0.99 kg/m(2), P = 0.05), finding which is of significance since obesity was described as being one of the risk factors for Crohn's disease. We are the first US group to report substantial cost savings, increased safety and patient satisfaction associated with accelerated infliximab infusion.

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... means to detect a fault condition, such as air in, or blockage of, the infusion line and to activate an...

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... means to detect a fault condition, such as air in, or blockage of, the infusion line and to activate an...

Effect of coefficient of viscosity and ambient temperature on the flow rate of drug solutions in infusion pumps.

PubMed

Kawabata, Yoshinori

2012-01-01

FOLFOX6 and FOLFIRI regimens are often selected as the first- or second-line treatment for advanced or recurrent colorectal cancer. Patients are now able to undergo at-home treatment by using a portable disposable infusion pump (SUREFUSER(®)A) for continuous intravenous infusion of 5-fluorouracil (5-FU). The duration of continuous 5-FU infusion is normally set at an average of 46 h, but large variations in the duration of infusion are observed. The relationship between the total volume of the drug solution in SUREFUSER(®)A and the duration of infusion was analyzed by regression analysis. In addition, multiple regression analysis of the total volume of the drug solution, dummy variables for temperature, and duration of infusion was carried out. The duration of infusion was affected by the coefficient of viscosity of the drug solution and the ambient temperature. The composition of the drug solutions and the ambient temperature must be considered to ensure correct duration of continuous infusion.

Ureteric bupivicaine infusion for loin pain haematuria syndrome.

PubMed

Ahmed, M; Acher, P; Deane, A M

2010-03-01

Loin pain haematuria syndrome is a common problem with complications including opiate dependence. Morbidity treatments include intra-ureteric capsaicin infusion, nephrectomy, autotransplantation and nephrolysis. We explored the use of flexible cystoscopic infusion of intra-ureteric bupivicaine. Patients presenting with chronic loin pain underwent urological and nephrological evaluation. Bupivicaine (0.5%, 20 ml) was infused via an intra-ureteric catheter under flexible cystoscopic guidance. Repeat infusions were offered if indicated. Sixteen of 17 patients with 1-year follow-up responded and were satisfied. Twelve of these required repeat infusions (mean, 2.9 infusions). The procedures were well tolerated by all patients without adverse effects. Intra-ureteric bupivicaine infusion has a place in the management of patients with chronic renal pain. It offers a minimally invasive alternative to other treatments. This procedure warrants further investigation within a randomised, controlled trial setting.

Transport of Nitric Oxide by Perfluorocarbon Emulsion

PubMed Central

Ortiz, Daniel; Briceño, Juan C.; Cabrales, Pedro

2014-01-01

Perfluorocarbon (PFC) emulsions can transport and release various gases based on concentration gradients. The objective of this study was to determine the possibility of carrying and delivering exogenous nitric oxide (NO) into the circulation by simply loading PFC emulsion with NO prior infusion. PFC was equilibrated with room air (PFC) or 300 ppm NO (PFC-NO) at atmospheric pressure. Isotonic saline solution was used as a volume control (Saline). PFC and PFC-NO were infused at a dose of 3.5 mL/kg in the hamster window chamber model. Blood chemistry, and systemic and microvascular hemodynamic response were measured. Infusion of PFC preloaded with NO reduced blood pressure, induced microvascular vasodilation and increased capillary perfusion; although these changes lasted less than 30 min post infusion. On the other hand, infusion of PFC (without NO) produced vasoconstriction; however, the vasoconstriction was followed by vasodilatation at 30 min post infusion. Plasma nitrite and nitrate increased 15 min after infusion of NO preloaded PFC compared to PFC, 60 min after infusion nitrite and nitrate were not different, and 90 min after infusion plasma S-nitrosothiols increased in both groups. Infusion of NO preloaded PFC resulted in acute vascular relaxation, where as infusion of PFC (without NO) produced vasoconstriction, potentially due to NO sequestration by the PFC micelles. The late effects of PFC infusion are due to NO redistribution and plasma S-nitrosothiols. Gas solubility in PFC can provide a tool to modulate plasma vasoactive NO forms availability and improve microcirculatory function and promote increased blood flow. PMID:23966236

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.

PubMed

Bailey, George P; Wood, David M; Archer, John R H; Rab, Edmund; Flanagan, Robert J; Dargan, Paul I

2017-02-01

Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion. Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml -1 (-6.7 to -2.3) for the first infusion, +0.2 mg ml -1 (-0.9 to +0.4) for the second infusion and -0.3 mg ml -1 (-0.6 to +0.2) for third and fourth infusions. There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. © 2016 The British Pharmacological Society.

A real-world, multi-site, observational study of infusion time and treatment satisfaction with rheumatoid arthritis patients treated with intravenous golimumab or infliximab.

PubMed

Daniel, Shoshana R; McDermott, John D; Le, Cathy; Pierce, Christine A; Ziskind, Michael A; Ellis, Lorie A

2018-05-25

To assess real-world infusion times for golimumab (GLM-IV) and infliximab (IFX) for rheumatoid arthritis (RA) patients and factors associated with treatment satisfaction. An observational study assessed infusion time including: clinic visit duration, RA medication preparation and infusion time, and infusion process time. Satisfaction was assessed by a modified Treatment Satisfaction Questionnaire for Medication (patient) and study-specific questionnaires (patient and clinic personnel). Comparative statistical testing for patient data utilized analysis of variance for continuous measures, and Fisher's exact or Chi-square test for categorical measures. Multivariate analysis was performed for the primary time endpoints and patient satisfaction. One hundred and fifty patients were enrolled from six US sites (72 GLM-IV, 78 IFX). The majority of patients were female (80.0%) and Caucasian (88.7%). GLM-IV required fewer vials per infusion (3.7) compared to IFX (4.9; p = .0001). Clinic visit duration (minutes) was shorter for GLM-IV (65.1) compared to IFX (153.1; p < .0001), as was total infusion time for RA medication (32.8 GLM-IV, 119.5 IFX; p < .0001) and infusion process times (45.8 GLM-IV, 134.1 IFX; p < .0001). Patients treated with GLM-IV reported higher satisfaction ratings with infusion time (p < .0001) and total visit time (p = .0003). Clinic personnel reported higher satisfaction with GLM-IV than IFX specific to medication preparation time, ease of mixing RA medication, frequency of patients requiring pre-medication, and infusion time. Findings may not be representative of care delivery for all RA infusion practices or RA patients. Shorter overall clinic visit duration, infusion process, and RA medication infusion times were observed for GLM-IV compared to IFX. A shorter duration in infusion time was associated with higher patient and clinic personnel satisfaction ratings.

Norepinephrine infusion with and without alpha-adrenergic blockade by phentolamine increases salivary alpha amylase in healthy men.

PubMed

Kuebler, Ulrike; von Känel, Roland; Heimgartner, Nadja; Zuccarella-Hackl, Claudia; Stirnimann, Guido; Ehlert, Ulrike; Wirtz, Petra H

2014-11-01

Mental stress reliably induces increases in salivary alpha amylase (sAA), a suggested surrogate marker for sympathetic nervous system (SNS) reactivity. While stress-induced sAA increases correlate with norepinephrine (NE) secretion, a potential mediating role of noradrenergic mechanisms remains unclear. In this study, we investigated for the first time in humans whether a NE-stress-reactivity mimicking NE-infusion with and without alpha-adrenergic blockade by phentolamine would induce changes in sAA. In a single-blind placebo-controlled within-subjects design, 21 healthy men (29-66 years) took part in three different experimental trials varying in terms of substance infusion with a 1-min first infusion followed by a 15-min second infusion: saline-infusion (trial-1), NE-infusion (5 μg/min) without alpha-adrenergic blockade (trial-2), and with phentolamine-induced non-selective blockade of alpha1- and alpha2-adrenergic receptors (trial-3). Saliva samples were collected immediately before, during, and several times after substance infusion in addition to blood pressure and heart rate readings. Experimental trials significantly differed in sAA reactivity to substance-infusion (p=.001) with higher sAA reactivity following NE-infusion with (trial-3; p=.001) and without alpha-adrenergic-blockade (trial-2; p=.004) as compared to placebo-infusion (trial-1); sAA infusion reactivity did not differ between trial-2 and trial-3 (p=.29). Effective phentolamine application was verified by blood pressure and heart rate infusion reactivity. Salivary cortisol was not affected by NE, either with or without alpha-adrenergic-blockade. We found that NE-infusion stimulates sAA secretion, regardless of co-administered non-selective alpha-adrenergic blockade by phentolamine, suggesting that the mechanism underlying stress-induced sAA increases may involve NE. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops.

PubMed

Takeda, Taizo; Sawada, Shoichi; Takeda, Setsuko; Kitano, Hiroya; Suzuki, Mikio; Kakigi, Akinobu; Takeuchi, Shunji

2003-08-01

In the present study, two experiments were performed to investigate the influence of OPC-31260 on experimentally induced endolymphatic hydrops in guinea pigs and the regulation of aquaporin-2 (AQP2) mRNA expression in the rat inner ear. In morphological studies, the increases in the ratios of the length of Reissner's membrane (IR-L) and the cross-sectional area of the scala media (IR-S) were quantitatively assessed among normal guinea pigs (normal ears) and three groups with hydropic ears: hydropic ears with no infusion (non-infusion hydropic ears), hydropic ears with an infusion of physiological saline into the scala tympani (saline-infused hydropic ears) and hydropic ears with infusion of 0.3% OPC-31260 into the scala tympani (OPC-infused hydropic ears). IR-Ls in the experimental groups were markedly larger than in the normal ear group, but there was no significant difference among the groups of non-infusion hydropic ears, saline-infused hydropic ears and OPC-infused hydropic ears. The IR-Ss of non-infusion hydropic ears and saline-infused hydropic ears (48.8-49.3%) were statistically different from that of normal ears (6.5%) (Dunnet multiple comparison test, P<0.01). However, IR-S of the OPC-infused hydropic ears (-14.8%) was significantly smaller than those of non-infusion hydropic ears and saline-infused hydropic ears (one-way ANOVA, P<0.01). In the quantitative polymerase chain reaction study, a comparison of the ratio of AQP2 and beta-actin mRNA (MAQP2/Mbeta-actin) was made between water-injected and OPC-31260-injected rats. An intravenous injection of OPC-31260 resulted in a significant decrease in MAQP2/Mbeta-actin both in the cochlea and in the endolymphatic sac (t-test, P<0.001). These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease.

Costs of providing infusion therapy for patients with inflammatory bowel disease in a hospital-based infusion center setting.

PubMed

Afzali, Anita; Ogden, Kristine; Friedman, Michael L; Chao, Jingdong; Wang, Anthony

2017-04-01

Inflammatory bowel disease (IBD) (e.g. ulcerative colitis [UC] and Crohn's disease [CD]) severely impacts patient quality-of-life. Moderate-to-severe disease is often treated with biologics requiring infusion therapy, adding incremental costs beyond drug costs. This study evaluates US hospital-based infusion services costs for treatment of UC or CD patients receiving infliximab or vedolizumab therapy. A model was developed, estimating annual costs of providing monitored infusions using an activity-based costing framework approach. Multiple sources (published literature, treatment product inserts) informed base-case model input estimates. The total modeled per patient infusion therapy costs in Year 1 with infliximab and vedolizumab was $38,782 and $41,320, respectively, and Year 2+, $49,897 and $36,197, respectively. Drug acquisition cost was the largest total costs driver (90-93%), followed by costs associated with hospital-based infusion provision: labor (53-56%, non-drug costs), allocated overhead (23%, non-drug costs), non-labor (23%, non-drug costs), and laboratory (7-10%, non-drug costs). Limitations included reliance on published estimates, base-case cost estimates infusion drug, and supplies, not accounting for volume pricing, assumption of a small hospital infusion center, and that, given the model adopts the hospital perspective, costs to the patient were not included in infusion administration cost base-case estimates. This model is an early step towards a framework to fully analyze infusion therapies' associated costs. Given the lack of published data, it would be beneficial for hospital administrators to assess total costs and trade-offs with alternative means of providing biologic therapies. This analysis highlights the value to hospital administrators of assessing cost associated with infusion patient mix to make more informed resource allocation decisions. As the landscape for reimbursement changes, tools for evaluating the costs of infusion therapy may help hospital administrators make informed choices and weigh trade-offs associated with providing infusion services for IBD patients.

Conservative management of bronchopulmonary artery perforation without associated haemothorax occurring at thoracentesis: a case report

PubMed Central

Chuang, Yao-Tsung; Tsao, Teng-Fu; Lin, Ming-Cheng

2010-01-01

Puncture or laceration of the pulmonary, intercostal, or peripheral vessels is an uncommon, but potentially life-threatening, complication of thoracentesis, which has been reported to result in severe haemothorax in 75% of patients. Damage to these vessels typically requires surgical intervention or intra-arterial embolisation. We report the successful non-surgical management of an unusual case of pulmonary artery perforation without concomitant haemothorax in an 82-year-old man who underwent thoracentesis. PMID:20529518

[Chemoembolization of symptomatic bone metastases: technical considerations and therapeutic effectiveness].

PubMed

Clarençon, F; Cormier, E; Di Maria, F; Sourour, N-A; Szatmary, Z; Rose, M; Chiras, J

2011-09-01

Chemoembolization of bone metastases is defined by the intraarterial perfusion of a chemotherapy agent followed by microparticles embolization to improve tissue impregnation. This technique increases the local concentration of the chemotherapy agent. Tumor response (stable or reduced tumor size) is achieved in 30-80% of cases with symptomatic relief in over 80% of cases. The indications, technical considerations, and effectiveness of this procedure will be reviewed. Copyright © 2011 Elsevier Masson SAS and Éditions françaises de radiologie. All rights reserved.

Repaglinide-induced factitious hypoglycemia.

PubMed

Hirshberg, B; Skarulis, M C; Pucino, F; Csako, G; Brennan, R; Gorden, P

2001-02-01

We report the first case of repaglinide-induced factitious hypoglycemia in a young male. This case posed a challenging diagnostic dilemma because commercial assays for repaglinide are not available. Furthermore, the patient had a series of positive diagnostic tests such as high proinsulin and localizing intra-arterial calcium stimulation suggestive of insulinoma. This case, again, demonstrates the importance of pure clinical judgment in the face of often-conflicting laboratory data in making a correct diagnosis and the requirement of definitive data for an appropriate therapeutic resolution.

Methods of preventing vinorelbine-induced phlebitis: an experimental study in rabbits

PubMed Central

Kohno, Emiko; Murase, Saori; Nishikata, Mayumi; Okamura, Noboru; Matzno, Sumio; Kuwahara, Takashi; Matsuyama, Kenji

2008-01-01

Purpose: In order to identify methods for preventing phlebitis caused by intravenous administration of vinorelbine (VNR), we established a procedure for estimating the severity of phlebitis in an animal model. Methods: Four different factors (administration rate, dilution, flushing, and infusion of fat emulsion) were evaluated for alleviation of phlebitis caused by VNR infusion. VNR was diluted with normal saline to prepare test solutions with concentrations of 0.6 mg/mL or 0.3 mg/mL for infusion into the auricular veins of rabbits. Two days after VNR infusion, the veins were subjected to histopathological examination. Results: VNR did not cause obvious loss of venous endothelial cells, the most sensitive and common feature of phlebitis, but VNR infusion led to inflammatory cell infiltration, edema, and epidermal degeneration. Tissue damage was significantly decreased by shortening the administration time and by diluting the VNR solution for infusion from 0.6 mg/mL to 0.3 mg/mL. However, there was no effect of flushing with normal saline after VNR infusion, while treatment with fat emulsion before and after VNR infusion only had a minimal effect. Conclusion: Rapid infusion and dilution are effective methods of reducing phlebitis caused by the infusion of VNR, but the efficacy of flushing with normal saline or infusion of fat emulsion was not confirmed. PMID:18695742

Ureteric bupivicaine infusion for loin pain haematuria syndrome

PubMed Central

Ahmed, P; Acher, P; Deane, AM

2010-01-01

INTRODUCTION Loin pain haematuria syndrome is a common problem with complications including opiate dependence. Morbidity treatments include intra-ureteric capsaicin infusion, nephrectomy, autotransplantation and nephrolysis. We explored the use of flexible cystoscopic infusion of intra-ureteric bupivicaine. PATIENTS AND METHODS Patients presenting with chronic loin pain underwent urological and nephrological evaluation. Bupivicaine (0.5%, 20 ml) was infused via an intra-ureteric catheter under flexible cystoscopic guidance. Repeat infusions were offered if indicated. RESULTS Sixteen of 17 patients with 1-year follow-up responded and were satisfied. Twelve of these required repeat infusions (mean, 2.9 infusions). The procedures were well tolerated by all patients without adverse effects. CONCLUSIONS Intra-ureteric bupivicaine infusion has a place in the management of patients with chronic renal pain. It offers a minimally invasive alternative to other treatments. This procedure warrants further investigation within a randomised, controlled trial setting. PMID:20353642

Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

PubMed

Yang, Xiaoliang; Saito, Ryuta; Nakamura, Taigen; Zhang, Rong; Sonoda, Yukihiko; Kumabe, Toshihiro; Forsayeth, John; Bankiewicz, Krystof; Tominaga, Teiji

2016-01-01

In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.

Association between continuous peripheral i.v. infusion of 3% sodium chloride injection and phlebitis in adults.

PubMed

Meng, Lina; Nguyen, Cherwyn M; Patel, Samit; Mlynash, Michael; Caulfield, Anna Finley

2018-03-01

One institution's experience with use of peripheral i.v. (PIV) catheters for prolonged infusions of 3% sodium chloride injection at rates up to 100 mL/hr is described. A prospective, observational, 13-month quality assurance project was conducted at an academic medical center to evaluate frequencies of patient and catheter phlebitis among adult inpatients who received both an infusion of 3% sodium chloride injection for a period of ≥4 hours through a dedicated PIV catheter and infusions of routine-care solutions (RCSs) through separate PIV catheters during the same hospital stay. Sixty patients received PIV infusions through a total of 291 catheters during the study period. The majority of patients (78%) received infusions of 3% sodium chloride injection for intracranial hypertension, with 30% receiving such infusions in the intensive care unit. Phlebitis occurred in 28 patients (47%) during infusions of 3% sodium chloride and 26 patients (43%) during RCS infusions ( p = 0.19). Catheter phlebitis occurred in 73 catheters (25%), with no significant difference in the frequencies of catheter phlebitis with infusion of 3% sodium chloride versus RCSs (30% [32 of 106 catheters]) versus 22% [41 of 185 catheters]), p = 0.16). Patient and catheter phlebitis rates were not significantly different with infusions of 3% sodium chloride injection versus RCSs, suggesting that an osmolarity cutoff value of 900 mOsm/L for peripheral infusions of hypertonic saline solutions may not be warranted. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Effect of infusion regime on doxorubicin pharmacokinetics in the cat.

PubMed

Hahn, K A; Frazier, D L; Cox, S K; Legendre, A M

1997-01-01

In the pharmacokinetic evaluation of a single doxorubicin dose calculated by body surface area (25 mg/m2) or body weight (1 mg/kg body weight) and given intravenously as a 10-, 15-, or 20-minute infusion, the rate of doxorubicin infusion (mg per minute per m2 or mg per minute per kg) correlated positively with clearance and the distribution rate constant alpha, and it inversely correlated with area under the plasma concentration versus time curve (AUC). These findings suggest that a slower infusion rate results in a greater AUC and longer distribution phase than a faster infusion rate and indicates the importance of normalizing dosage regimes by infusion rate rather than by infusion duration when considering dose-response phenomena in veterinary patients.

Gravid Anopheles gambiae sensu stricto avoid ovipositing in Bermuda grass hay infusion and it's volatiles in two choice egg-count bioassays.

PubMed

Eneh, Lynda K; Okal, Michael N; Borg-Karlson, Anna-Karin; Fillinger, Ulrike; Lindh, Jenny M

2016-05-12

A number of mosquito species in the Culex and Aedes genera prefer to lay eggs in Bermuda grass (Cynodon dactylon) hay infusions compared to water alone. These mosquitoes are attracted to volatile compounds from the hay infusions making the infusions effective baits in gravid traps used for monitoring vectors of arboviral and filarial pathogens. Since Bermuda grass is abundant and widespread, it is plausible to explore infusions made from it as a potential low cost bait for outdoor monitoring of the elusive malaria vector Anopheles gambiae s.s. This study investigated preferential egg laying of individual An. gambiae s.s. in hay infusion or in tap water treated with volatiles detected in hay infusion headspace compared to tap water alone, using two-choice egg-count bioassays. Infusions were prepared by mixing 90 g of dried Bermuda grass (hay) with 24 L of unchlorinated tap water in a bucket, and leaving it for 3 days at ambient temperature and humidity. The volatiles in the headspace of the hay infusion were sampled with Tenax TA traps for 20 h and analysed using gas chromatography coupled to mass spectrometry. In total, 18 volatiles were detected in the infusion headspace. Nine of the detected compounds and nonanal were selected for bioassays. Eight of the selected compounds have previously been suggested to attract/stimulate egg laying in An. gambiae s.s. Gravid females were significantly (p < 0.05) less likely to lay eggs in hay infusion dilutions of 25, 50 and 100 % and in tap water containing any of six compounds (3-methylbutanol, phenol, 4-methylphenol, nonanal, indole, and 3-methylindole) compared to tap water alone. The oviposition response to 10 % hay infusion or any one of the remaining four volatiles (4-hepten-1-ol, phenylmethanol, 2-phenylethanol, or 4-ethylphenol) did not differ from that in tap water. Anopheles gambiae s.s. prefers to lay eggs in tap water rather than Bermuda grass hay infusion. This avoidance of the hay infusion appears to be mediated by volatile organic compounds from the infusion. It is, therefore, unlikely that Bermuda grass hay infusion as formulated and used in gravid traps for Culex and Aedes mosquitoes will be suitable baits for monitoring gravid An. gambiae s.s.

A study on interactions between the insoluble fractions of different coffee infusions and major cocoa free antioxidants and different coffee infusions and dark chocolate.

PubMed

Çelik, Ecem Evrim; Gökmen, Vural

2018-07-30

This study aimed to investigate the interactions between insoluble fractions of different coffee infusions and major cocoa free antioxidants, catechin and epicatechin, as well as the interactions between different coffee infusions and dark chocolate. Espresso, filtered coffee, French press and Turkish coffee were used for this purpose. Antioxidant capacity (AC) measurements were performed by monitoring the percentage inhibition of 2,2-Diphenyl-1-picrylhydrazil (DPPH) radical. Multivariate approach was adopted for experimental design and data analysis steps. In dry basis, the AC values of infusions (mmol Trolox/kg) were ranged between 953 ± 2.6 and 1184 ± 11.3, while the AC values for their insoluble fractions were ranged between 45 ± 0.0 and 105-1.3. Interactions between the insoluble fractions of coffee infusions and catechins were synergistic for espresso and additive/antagonistic for the other infusions. Interactions between coffee infusions and chocolate were synergistic for French press and Turkish coffee and additive/antagonistic for the other infusions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anti-Aging Effects of the Hanwoo Leg Bone, Foot and Tail Infusions (HLI, HFI and HTI) on Skin Fibroblast.

PubMed

Seol, Ja Young; Yoon, Ji Young; Jeong, Hee Sun; Joo, Nami; Choi, Soon Young

2016-01-01

Many researchers revealed that collagen contribute to maintaining the skin's elasticity and inhibit wrinkling of skin. Korean native cattle (Hanwoo) bone (leg bone, foot and tail) infusion contains the various inorganic materials, collagen and chondroitin sulfate. All of this, a large quantity of collagen is included in Hanwoo infusion. Therefore, this study emphasized on the effects of collagen in the Hanwoo bone infusion. For the first time, Hanwoo bone infusions were directly added to the media of Human Dermal Fibroblast (NHDF-c) to test anti-aging effects. First, it was identified that growth rate of skin fibroblast was increased. Furthermore, the Hanwoo bone infusion increased a 50% of fibroblast collagen synthesis. Also, suppression of skin fibroblast aging was confirmed by treatment Hanwoo bone infusion. In conclusion, this study demonstrates the effects of infusion made from Hanwoo leg bone, foot and tail on anti-aging, wrinkle inhibiting and skin fibroblast elasticity maintaining. Therefore, this study identified that traditional infusion has effects that are good for skin elasticity.

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme.

PubMed

Bodensteiner, David; Scott, C Ronald; Sims, Katherine B; Shepherd, Gillian M; Cintron, Rebecca D; Germain, Dominique P

2008-05-01

To determine if enzyme replacement therapy, involving intravenous infusions of recombinant human alpha-galactosidase A (agalsidase beta; Fabrazyme), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. The rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26-66 years) were enrolled. During rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. Agalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

Rapid-infusion rituximab in lymphoma treatment: 2-year experience in a single institution.

PubMed

Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-05-01

Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy.

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

NASA Technical Reports Server (NTRS)

Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

1995-01-01

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

Smart syringe pumps for drug infusion during dental intravenous sedation

PubMed Central

Lee, Kiyoung

2016-01-01

Dentists often sedate patients in order to reduce their dental phobia and stress during dental treatment. Sedatives are administered through various routes such as oral, inhalation, and intravenous routes. Intravenous administration has the advantage of rapid onset of action, predictable duration of action, and easy titration. Typically, midazolam, propofol or dexmedetomidine are used as intravenous sedatives. Administration of these sedatives via infusion by using a syringe pump is more effective and successful than infusing them as a bolus. However, during intravenous infusion of sedatives or opioids using a syringe pump, fatal accidents may occur due to the clinician's carelessness. To prevent such risks, smart syringe pumps have been introduced clinically. They allow clinicians to perform effective sedation by using a computer to control the dose of the drug being infused. To ensure patient safety, various alarm features along with a drug library, which provides drug information and prevents excessive infusion by limiting the dose, have been added to smart pumps. In addition, programmed infusion systems and target-controlled infusion systems have also been developed to enable effective administration of sedatives. Patient-controlled infusion, which allows a patient to control his/her level of sedation through self-infusion, has also been developed. Safer and more successful sedation may be achieved by fully utilizing these new features of the smart pump. PMID:28884149

Bioactive compounds and antioxidant activity of wolfberry infusion

PubMed Central

Sun, Yujing; Rukeya, Japaer; Tao, Wenyang; Sun, Peilong; Ye, Xingqian

2017-01-01

An infusion of the wolfberry (Lycium barbarum L.) is a traditional Asian herbal tea. This is the most commonly consumed form of dried wolfberry worldwide, yet little scientific information on wolfberry infusions is available. We investigated the effects of making infusions with hot water on the color, the content of bioactive compounds (polysaccharides, polyphenols, flavonoids and carotenoids) and the antioxidant ability of wolfberry infusions. The contents of bioactive compounds and the antioxidant activity of a wolfberry infusion increased with increased infusion temperature and time. Total polysaccharides content (TPOC), total polyphenols (TPC), total flavonoids (TFC) and total carotenoids contents (TCC) were important for determining the antioxidant capacity of wolfberry infusions with the contribution to antioxidant activity in the order TPC > TFC > TCC > TPOC. Hierarchical cluster analysis indicated preparation conditions of 100 °C for 1~3 h, 90 °C for 2~3 h and 80 °C for 2.5~3 h were equivalent as regards the value of TPC, TPOC, TFC, TCC, FRAP, DPPH and ABTS. The results of this study suggest the length of time of making a wolfberry infusion in actual real life practice is too short and different dietary habits associated with the intake of wolfberry infusion might provide the same bioactive nutrients. PMID:28102295

A study of estrogen metabolic clearance rates and transfer factors

PubMed Central

Hembree, W. C.; Bardin, C. W.; Lipsett, M. B.

1969-01-01

We have attempted to measure the metabolic clearance rates (MCR) and the transfer factors of estradiol (E2) and estrone (E1) during 2-hr and 12-hr infusions. When estradiol-3H was infused for 2 hr, apparent equilibrium was reached at 70 min; the 12-hr infusions showed that plasma estradiol-3H levels increased slowly throughout the infusion. When estrone-3H was infused, constancy of estrone-3H levels was not attained in either the 2-hr infusions or in the two 12-hr infusions. The tritium level in the metabolite of the infused estrogen did not become constant in 50% of the short infusions and increased during all the long infusions. Thus, the conversion ratios CE1E2 and CE2E1 continually changed and transfer factors could not be calculated. The apparent “MCR'S” calculated on the basis of the 2-hr studies expressed as liters/24 hr per m2 ±SD were: “MCRE1” (women) 980 ±94, (men) 1170 ±95; “MCRE2” (women) 615 ±17, (men) 830 ±30. The estradiol “MCR's” differed significantly between men and women. “MCRE2” was the same using either estradiol-14C or -3H and was unchanged by the infusion of 170 μg of estradiol daily. Postmenopausal women had estrogen “MCR's” in the same range as premenopausal women. Excess glucocorticoids increased the “MCRE2.” PMID:5822587

Continuous Intravenous Sub-Dissociative Dose Ketamine Infusion for Managing Pain in the Emergency Department

PubMed Central

Drapkin, Jefferson; Likourezos, Antonios; Beals, Tyler; Monfort, Ralph; Fromm, Christian; Marshall, John

2018-01-01

Introduction Our objective was to describe dosing, duration, and pre- and post-infusion analgesic administration of continuous intravenous sub-dissociative dose ketamine (SDK) infusion for managing a variety of painful conditions in the emergency department (ED). Methods We conducted a retrospective chart review of patients aged 18 and older presenting to the ED with acute and chronic painful conditions who received continuous SDK infusion in the ED for a period over six years (2010–2016). Primary data analyses included dosing and duration of infusion, rates of pre- and post-infusion analgesic administration, and final diagnoses. Secondary data included pre- and post-infusion pain scores and rates of side effects. Results A total of 104 patients were enrolled in the study. Average dosing of SDK infusion was 11.26 mg/hr, and the mean duration of infusion was 135.87 minutes. There was a 38% increase in patients not requiring post-infusion analgesia. The average decrease in pain score was 5.04. There were 12 reported adverse effects, with nausea being the most prevalent. Conclusion Continuous intravenous SDK infusion has a role in controlling pain of various etiologies in the ED with a potential to reduce the need for co-analgesics or rescue analgesic administration. There is a need for more robust, prospective, randomized trials that will further evaluate the analgesic efficacy and safety of this modality across a wide range of pain syndromes and different age groups in the ED. PMID:29760856

Continuous Lidocaine Infusions to Manage Opioid-Refractory Pain in a Series of Cancer Patients in a Pediatric Hospital.

PubMed

Gibbons, Kathleen; DeMonbrun, Andrea; Beckman, Elizabeth J; Keefer, Patricia; Wagner, Deb; Stewart, Margaret; Saul, D'Anna; Hakel, Stephanie; Liu, My; Niedner, Matthew

2016-07-01

Research on the safety and efficacy of continuous lidocaine infusions (CLIs) for the treatment of pain in the pediatric setting is limited. This article describes a series of pediatric oncology patients who received lidocaine infusions for refractory, longstanding, cancer-related pain. This is a retrospective review of patients who underwent lidocaine infusions to manage severe, opioid-refractory, cancer-related pain. Four patients ranging in age from 8 to 18 years were admitted to a pediatric hospital for their medical conditions and/or pain management. Structured chart review established demographic and diagnosis information, infusion rates, side effects, and efficacy of infusions in providing pain relief. Lidocaine bolus doses, infusion rates, serum concentrations, and subjective pain scores were analyzed. Median pain scores prior to lidocaine infusions were 8/10, falling to 2/10 at the infusion termination (P < 0.003), and rising to 3/10 in the first 24 hr after lidocaine (P < 0.029 compared to preinfusion pain). The infusions were generally well tolerated, with few side effects noted. In most cases, the improvement in pain scores persisted beyond termination of the infusion. CLIs were a helpful adjuvant in the four cases presented and may be an effective therapy for a more diverse array of refractory cancer pain. The majority of patients experienced pain relief well beyond the metabolic elimination of the lidocaine, corroborating a modulation effect on pain windup. Additional research regarding infusion rates, serum concentrations, side effects, and outpatient follow-up in a larger group of patients will provide additional insight into the role and safety of this therapy in children. © 2016 Wiley Periodicals, Inc.

Transarterial Infusion Chemotherapy Using Cisplatin-Lipiodol Suspension With or Without Embolization for Unresectable Hepatocellular Carcinoma

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

Kawaoka, Tomokazu; Aikata, Hiroshi, E-mail: aikata@hiroshima-u.ac.jp; Takaki, Shintaro

We evaluate the long-term prognosis and prognostic factors in patients treated with transarterial infusion chemotherapy using cisplatin-lipiodol (CDDP/LPD) suspension with or without embolization for unresectable hepatocellular carcinoma (HCC). Study subjects were 107 patients with HCC treated with repeated transarterial infusion chemotherapy alone using CDDP/LPD (adjusted as CDDP 10mg/LPD 1ml). The median number of transarterial infusion procedures was two (range, one to nine), the mean dose of CDDP per transarterial infusion chemotherapy session was 30 mg (range, 5.0-67.5 mg), and the median total dose of transarterial infusion chemotherapy per patient was 60 mg (range, 10-390 mg). Survival rates were 86% atmore » 1 year, 40% at 3 years, 20% at 5 years, and 16% at 7 years. For patients with >90% LPD accumulation after the first transarterial infusion chemotherapy, rates were 98% at 1 year, 60% at 3 years, and 22% at 5 years. Multivariate analysis identified >90% LPD accumulation after the first transarterial infusion chemotherapy (p = 0.001), absence of portal vein tumor thrombosis (PVTT; p < 0.001), and Child-Pugh class A (p = 0.012) as independent determinants of survival. Anaphylactic shock was observed in two patients, at the fifth transarterial infusion chemotherapy session in one and the ninth in the other. In conclusion, transarterial infusion chemotherapy with CDDP/LPD appears to be a useful treatment option for patients with unresectable HCC without PVTT and in Child-Pugh class A. LPD accumulation after the first transarterial infusion chemotherapy is an important prognostic factor. Careful consideration should be given to the possibility of anaphylactic shock upon repeat infusion with CDDP/LPD.« less

The effects of sub-anesthetic ketamine infusions on motivation to quit and cue-induced craving in cocaine dependent research volunteers

PubMed Central

Dakwar, Elias; Levin, Frances; Foltin, Richard W.; Nunes, Edward V.; Hart, Carl L.

2014-01-01

Background Cocaine dependence involves problematic neuroadaptations that may be responsive to modulation of glutamatergic circuits. This investigation examined the effects of sub-anesthetic ketamine infusions on motivation for quitting cocaine and on cue-induced craving in cocaine dependent participants, 24 hours post-infusion. Methods Eight volunteers with active DSM-IV cocaine dependence not seeking treatment or abstinence were entered into this crossover, double-blind trial. Three 52 minute intravenous infusions were administered: ketamine (0.41 mg/kg or 0.71 mg/kg) or lorazepam 2 mg, counterbalanced into three orderings in which ketamine 0.41 mg/kg always preceded the 0.71 mg/kg dose. Infusions were separated by 48 hours, and assessments occurred at baseline and at 24 hours post-infusion. Outcomes were change between post-infusion and pre-infusion values for 1) motivation to quit cocaine scores using the University of Rhode Island Change Assessment (URICA), and 2) sums of visual analogue scale (VAS) craving ratings administered during cue exposure. Results Compared to the active control lorazepam, a single ketamine infusion (0.41 mg/kg) led to a mean 3.9 points gain in URICA (p=0.012), which corresponds to an approximately 60% increase over preceding values. There was a reduction of comparable magnitude in cue-induced craving (p=0.012). A subsequent ketamine infusion (0.71 mg/kg) led to further reductions in cue-induced craving compared to the control. Infusions were well tolerated. Conclusions Sub-anesthetic ketamine demonstrated promising effects on motivation to quit cocaine and on cue-induced craving, 24 hours post-infusion. Research is needed to expand on these preliminary results, and to evaluate the efficacy of this intervention in clinical settings. PMID:24035344

Analysis of the intraocular jet flows and pressure gradients induced by air and fluid infusion: mechanism of focal chorioretinal damage.

PubMed

Kim, Yong Joon; Jo, Sungkil; Moon, Daruchi; Joo, Youngcheol; Choi, Kyung Seek

2014-05-01

To comprehend the mechanism of focal chorioretinal damage by analysis of the pressure distribution and dynamic pressure induced by infused air during fluid-air exchange. A precise simulation featuring a model eye and a fluid circuit was designed to analyze fluid-air exchange. The pressure distribution, flow velocity, and dynamic pressure induced by infusion of air into an air-filled eye were analyzed using an approach based on fluid dynamics. The size of the port and the infusion pressure were varied during simulated iterations. We simulated infusion of an air-filled eye with balanced salt solution (BSS) to better understand the mechanism of chorioretinal damage induced by infused air. Infused air was projected straight toward a point on the retina contralateral to the infusion port (the "vulnerable point"). The highest pressure was evident at the vulnerable point, and the lowest pressure was recorded on most retinal areas. Simulations using greater infusion pressure and a port of larger size were associated with elevations in dynamic pressure and the pressure gradient. The pressure gradients were 2.8 and 5.1 mm Hg, respectively, when infusion pressures of 30 and 50 mm Hg were delivered through a 20-gauge port. The pressure gradient associated with BSS infusion was greater than that created by air, but lasted for only a moment. Our simulation explains the mechanism of focal chorioretinal damage in numerical terms. Infused air induces a prolonged increase in focal pressure on the vulnerable point, and this may be responsible for visual field defects arising after fluid-air exchange. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Continuous infusion of amphotericin B: preliminary experience at Faculdade de Medicina da Fundação ABC.

PubMed

Uehara, Roberto Palermo; Sá, Victor Hugo Lara de; Koshimura, Erika Tae; Prudente, Fernanda Vilas Boas; Tucunduva, Luciana Tomanik Cardozo de Mello; Gonçalves, Marina Sahade; Samano, Eliana Sueco Tibana; del Giglio, Auro

2005-09-01

Intravenous amphotericin B deoxycholate (AmB-D) infusions, usually given over 4 hours, frequently induce nephrotoxicity and undesirable infusion-related side effects such as rigors and chills. There is evidence in the literature that the use of AmB-D in the form of continuous 24-hour infusion is less toxic than the usual four-hour infusion of this drug. Our objective was to evaluate the efficacy and safety of continuous infusion of AmB-D for the treatment of persistent fever in neutropenic patients with hematological malignancies after chemotherapy. Observational retrospective analysis of our experience with continuous infusion of AmB-D, at Faculdade de Medicina da Fundação ABC and Hospital Estadual Mário Covas in Santo André. From October 2003 to May 2004, 12 patients with hematological malignancies and chemotherapy-induced neutropenia received 13 cycles of continuous infusion of AmB-D. The median dose of AmB-D was 0.84 mg/kg/day (0.33 to 2.30 mg/kg/day). Concomitant use of nephrotoxic medications occurred in 92% of the cycles. Nephrotoxicity occurred in 30.76% of the cycles, hypokalemia in 16.67%, hepatotoxicity in 30% and adverse infusion-related events in 23%. All patients survived for at least seven days after starting continuous infusion of AmB-D, and clinical resolution occurred in 76% of the cycles. Continuous infusion of AmB-D can be used in our Institution as an alternative to the more toxic four-hour infusion of AmB-D and possibly also as an alternative to the more expensive liposomal formulations of the drug.

Is continuous infusion of imipenem always the best choice?

PubMed

Suchánková, Hana; Lipš, Michal; Urbánek, Karel; Neely, Michael N; Strojil, Jan

2017-03-01

Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT >MIC , 40%fT >MIC and 100%fT >MIC . For the target of 40%fT >MIC , all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT >MIC target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT >MIC and 100%fT >MIC were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Magnetic Resonance Imaging-Based Assessment of Gadolinium-Conjugated Diethylenetriamine Penta-Acetic Acid Test-Infusion in Detecting Dysfunction of Convection-Enhanced Delivery Catheters.

PubMed

van Putten, Erik H P; Wembacher-Schröder, Eva; Smits, Marion; Dirven, Clemens M F

2016-05-01

In a phase 1 trial conducted at our institute, convection-enhanced delivery (CED) was used to administrate the Delta-24-RGD adenovirus in patients with a recurrent glioblastoma multiforme. Infusion of the virus was preceded by a gadolinium-conjugated diethylenetriamine penta-acetic acid (Gd-DTPA) test-infusion. In the present study, we analyzed the results of Gd-DTPA test infusion through 50 catheters. Thirteen adults with a recurrent glioblastoma multiforme were enrolled in a larger phase 1 multicenter, dose-finding study, in which a conditionally replication-competent adenovirus was administered by CED. Up to 4 infusion catheters per patient were placed intra- and/or peritumorally. Before infusion of the virus, a Gd-DTPA infusion was performed for 6 hours, directly followed by a MRI scan. The MRIs were evaluated for catheter position, Gd-DTPA distribution outcome, and contrast leakage. Leakage of Gd-DTPA into the cerebrospinal fluid was detected in 17 of the 50 catheters (34%). Sulcus crossing was the most frequent cause of leakage. In 8 cases, leakage could only be detected on the fluid-attenuated inversion recovery sequence. Nonleaking catheters showed a significantly larger Gd-DTPA distribution fraction (volume of distribution/volume of infusion) than leaking catheters (P = 0.009). A significantly lower volume of distribution/volume of infusion was observed in intratumoral catheters, compared with peritumoral catheters (P = 0.004). Gd-DTPA test infusion did not result in significant changes in Karnofsky Performance Score and Neurological Status. Pre-CED treatment infusion of Gd-DTPA is an adequate and safe method to identify dysfunctional catheters. The use of an optimized drug delivery catheter is necessary to reduce leakage and improve the efficacy of intracerebral drug infusion. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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.

An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose

PubMed Central

Bailey, George P.; Wood, David M.; Archer, John R. H.; Rab, Edmund; Flanagan, Robert J.

2016-01-01

Background Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight‐based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance. Methods A 6‐month single‐centre prospective study was undertaken at a UK teaching hospital. After preparation, 5‐ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high‐performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight‐based dose and volume were made for each infusion. Results Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10–20% for 27 (30%) infusions, 20.1–50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of −3.6 mg ml−1 (−6.7 to −2.3) for the first infusion, +0.2 mg ml−1 (−0.9 to +0.4) for the second infusion and −0.3 mg ml−1 (−0.6 to +0.2) for third and fourth infusions. Conclusion There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors. PMID:27558662

Effect of intravenous zoledronic acid infusion on electrocardiographic parameters in patients with osteoporosis.

PubMed

Aktas, I; Nazikoglu, C; Kepez, A; Ozkan, F U; Kaysin, M Y; Akpinar, P; Dogan, Z; Ileri, C; Saymaz, S; Erdogan, O

2016-12-01

We evaluated the effects of zoledronic acid (ZA) therapy on electrocardiographic (ECG) parameters for the first time in the literature. Measurements were performed on ECGs obtained before and after ZA infusion on the same day as well as 1 month after the infusion. ZA infusion did not have any short- or long-term effect on any parameter that might be associated with the tendency for atrial fibrillation or ventricular arrhythmias. The aim of the present study was to evaluate the early and late effects of ZA therapy on ECG parameters which might be associated with the tendency for atrial and ventricular arrhythmias. Consecutive patients with osteoporosis who were admitted to our clinic between December 2013 and December 2014 and who were scheduled to receive ZA infusion constituted our study population. Twelve-lead surface ECGs were obtained from all patients before and after ZA infusion on the same day as well as 1 month after the infusion. All ECG parameters were measured and compared with each other for each patient. Data of 100 patients were used in the analysis (9 male; 70.5 ± 11.6 years of age). There were no significant differences between repeated measurements regarding pmax, pmin, and p dispersion values. QT max and QT min values were significantly increased after infusion; however, there were no significant changes in QT dispersion, Tp-e interval, and Tp-e dispersion values. ZA infusion did not affect P wave dispersion both at the immediate post-infusion period and 1 month after infusion. QT values were significantly increased early after ZA infusion; however, there were no significant differences in parameters reflecting disparity of ventricular recovery times and transmural dispersion of ventricular repolarization. Based on these observations, it may be suggested that ZA infusion did not have any short- or long-term effect on any parameter that might be associated with the tendency for atrial fibrillation or ventricular arrhythmias.

[Portable elastomeric infusion system applied to patients with knee prosthesis].

PubMed

Soler, Gemma; Quiles, Olga; Nicolau, Agnes; Faura, Teresa; Moreno, Cristina

2007-03-01

An LV infuser consists of an infusion pump which can administer medicines via various methods: intravenous, epidural, subdural, o subcutaneous. Its usefulness is based on the administration of medicines such as oncological drugs and/or analgesic by means of a continuous infusion.

How to Keep an Infusion Log: Intravenous Immune Globulin (IVIG)

MedlinePlus

How to keep an INFUSION LOG Intravenous Immune Globulin (IVIG) How to keep an INFUSION LOG The Value of Keeping Records Excellence in health care ... keeping track of your Intravenous Immune Globulin (IVIG) infusions. Each of the manufacturers prepares IVIG in a ...

21 CFR 880.5965 - Subcutaneous, implanted, intravascular infusion port and catheter.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Subcutaneous, implanted, intravascular infusion... Hospital and Personal Use Therapeutic Devices § 880.5965 Subcutaneous, implanted, intravascular infusion port and catheter. (a) Identification. A subcutaneous, implanted, intravascular infusion port and...

21 CFR 870.1800 - Withdrawal-infusion pump.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Withdrawal-infusion pump. 870.1800 Section 870...) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1800 Withdrawal-infusion pump. (a) Identification. A withdrawal-infusion pump is a device designed to inject accurately drugs...

21 CFR 880.5965 - Subcutaneous, implanted, intravascular infusion port and catheter.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Subcutaneous, implanted, intravascular infusion... Hospital and Personal Use Therapeutic Devices § 880.5965 Subcutaneous, implanted, intravascular infusion port and catheter. (a) Identification. A subcutaneous, implanted, intravascular infusion port and...

Evaluation and comparison of safety, convenience and cost of administering intravenous pamidronate infusions to children in the home and ambulatory care settings.

PubMed

Rush, Eric T; DeHaai, Kristi; Kreikemeier, Rose M; Lutz, Richard E

2012-01-01

The use of bisphosphonates in children to treat low bone mineral density has increased. Safety and efficacy of pamidronate has been previously demonstrated. However, little research has been done on pamidronate infusion in the home health setting for patients with metabolic bone disease. Data were collected via a survey to assess satisfaction and convenience of infusions. Adverse events were measured by collecting calcium levels before and after infusions. Infusion costs were estimated from the standard orders from one home health agency and our infusion center. We found no difference in the rates of hypocalcemia between the two groups. The survey results showed high satisfaction for both groups, with higher scores in the home health group for convenience and stress. Home health infusions showed lower cost and less absenteeism from school and work. Home health-based pamidronate infusion appears to be safe, less expensive, and is associated with high patient satisfaction.

Pre-electroconvulsive shock administration of calcium channel blockers reduces retrograde amnesia induced by ECS.

PubMed

Sushma, M; Sudha, S; Guido, S

2004-11-01

Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.

Intravenous infusion of apoptotic cells simultaneously with allogeneic hematopoietic grafts alters anti-donor humoral immune responses.

PubMed

Perruche, Sylvain; Kleinclauss, François; Bittencourt, Marcelo de Carvalho; Paris, Dominique; Tiberghien, Pierre; Saas, Philippe

2004-08-01

Intravenous infusion of apoptotic donor or third-party leukocytes simultaneously with an allogeneic donor bone marrow (BM) graft favors engraftment across major histocompatibility barriers. While verifying that such apoptotic cell infusion might not also be associated with antibody (Ab)-mediated allo-immune responses, we found, rather strikingly, that apoptotic cell infusion could in fact successfully prevent a humoral allo-immunization against a BM graft in mice. Indeed, among recipients having rejected their BM graft, prior apoptotic cell infusion was associated with a near absence of Ab-mediated allo-responses, while such an immunization was frequently observed in the absence of apoptotic cell infusion. This was also observed when infusing host apoptotic cells, thus showing that the prevention of immunization was linked to the apoptotic state of the cells rather than mediated by residual anti-recipient activity. In vivo anti-transforming growth factor-beta (TGF-beta) treatment resulted in the loss of this apoptotic cell infusion-associated protective effect on humoral allo-responses. Further studies will determine whether apoptotic cell infusion, in addition to hematopoietic graft facilitation might also contribute to preventing deleterious Ab-mediated allo-responses in various transplantation settings.

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

NASA Technical Reports Server (NTRS)

Watenpaugh, Donald E.; Vissing, Susanne F.; Lane, Lynda D.; Buckey, Jay C.; Firth, Brian G.; Erdman, William; Hargens, Alan R.; Blomqvist, C. Gunnar

1995-01-01

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

Habitat discrimination by gravid Anopheles gambiae sensu lato – a push-pull system

PubMed Central

2014-01-01

Background The non-random distribution of anopheline larvae in natural habitats suggests that gravid females discriminate between habitats of different quality. Whilst physical and chemical cues used by Culex and Aedes vector mosquitoes for selecting an oviposition site have been extensively studied, those for Anopheles remain poorly explored. Here the habitat selection by Anopheles gambiae sensu lato (s.l.), the principal African malaria vector, was investigated when presented with a choice of two infusions made from rabbit food pellets, or soil. Methods Natural colonization and larval survival was evaluated in artificial ponds filled randomly with either infusion. Dual-choice, egg-count bioassays evaluated the responses of caged gravid females to (1) two- to six-day old infusions versus lake water; (2) autoclaved versus non-autoclaved soil infusions; and assessed (3) the olfactory memory of gravid females conditioned in pellet infusion as larvae. Results Wild Anopheles exclusively colonized ponds with soil infusion and avoided those with pellet infusion. When the individual infusions were tested in comparison with lake water, caged An. gambiae sensu stricto (s.s.) showed a dose response: females increasingly avoided the pellet infusion with increasing infusion age (six-day versus lake water: odds ratio (OR) 0.22; 95% confidence interval (CI) 0.1-0.5) and showed increasing preference to lay eggs as soil infusion age increased (six-day versus lake water: OR 2.1; 95% CI 1.4-3.3). Larvae survived in soil infusions equally well as in lake water but died in pellet infusions. Anopheles gambiae s.s. preferred to lay eggs in the non-autoclaved soil (OR 2.6; 95% CI 1.8-3.7) compared with autoclaved soil. There was no change in the avoidance of pellet infusion by individuals reared in the infusion compared with those reared in lake water. Conclusion Wild and caged An. gambiae s.l. females discriminate between potential aquatic habitats for oviposition. These choices benefit the survival of the offspring. Although the study was not designed to distinguish between stimuli that acted over a distance or on contact, it could be demonstrated that the choice of habitat is mediated by chemical cues based on both preference and avoidance. These cues, if identified, might be developed for ‘push-pull’ strategies to improve malaria vector monitoring and control. PMID:24693951

78 FR 79469 - Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

...] Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop AGENCY: Food and... Infusions.'' The purpose of the public workshop is to identify and discuss potential risk mitigation...) (Human) infusion. Complications of hemolysis include severe anemia requiring transfusion, renal failure...

Distribution of adoptively transferred porcine T-lymphoblasts tracked by (18)F-2-fluoro-2-deoxy-D-glucose and position emission tomography.

PubMed

Eriksson, Olof; Sadeghi, Arian; Carlsson, Björn; Eich, Torsten; Lundgren, Torbjörn; Nilsson, Bo; Tötterman, Thomas; Korsgren, Olle; Sundin, Anders

2011-08-01

Autologous or allogeneic transfer of tumor-infiltrating T-lymphocytes is a promising treatment for metastatic cancers, but a major concern is the difficulty in evaluating cell trafficking and distribution in adoptive cell therapy. This study presents a method of tracking transfusion of T-lymphoblasts in a porcine model by (18)F-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and positron emission tomography. T-lymphoblasts were labeled with the positron-emitting tracer [(18)F]FDG through incubation. The T-lymphoblasts were administered into the bloodstream, and the distribution was followed by positron emission tomography for 120 min. The cells were administered either intravenously into the internal jugular vein (n=5) or intraarterially into the ascending aorta (n=1). Two of the pigs given intravenous administration were pretreated with low-molecular-weight dextran sulphate. The cellular kinetics and distribution were readily quantifiable for up to 120 min. High (78.6% of the administered cells) heterogeneous pulmonary uptake was found after completed intravenous transfusion. The pulmonary uptake was decreased either by preincubating and coadministrating the T-lymphoblasts with low-molecular-weight dextran sulphate or by administrating them intraarterially. The present work shows the feasibility of quantitatively monitoring and evaluating cell trafficking and distribution following administration of [(18)F]FDG-labeled T-lymphoblasts. The protocol can potentially be transferred to the clinical setting with few modifications. Copyright © 2011 Elsevier Inc. All rights reserved.

Orthotopic glioblastoma stem-like cell xenograft model in mice to evaluate intra-arterial delivery of bevacizumab: from bedside to bench.

PubMed

Burkhardt, Jan-Karl; Hofstetter, Christoph P; Santillan, Alejandro; Shin, Benjamin J; Foley, Conor P; Ballon, Douglas J; Pierre Gobin, Y; Boockvar, John A

2012-11-01

Bevacizumab (BV), a humanized monocolonal antibody directed against vascular endothelial growth factor (VEGF), is a standard intravenous (IV) treatment for recurrent glioblastoma multiforme (GBM), that has been introduced recently as an intra-arterial (IA) treatment modality in humans. Since preclinical models have not been reported, we sought to develop a tumor stem cell (TSC) xenograft model to investigate IA BV delivery in vivo. Firefly luciferase transduced patient TSC were injected into the cortex of 35 nude mice. Tumor growth was monitored weekly using bioluminescence imaging. Mice were treated with either intraperitoneal (IP) or IA BV, with or without blood-brain barrier disruption (BBBD), or with IP saline injection (controls). Tumor tissue was analyzed using immunohistochemistry and western blot techniques. Tumor formation occurred in 31 of 35 (89%) mice with a significant signal increase over time (p=0.018). Post mortem histology revealed an infiltrative growth of TSC xenografts in a similar pattern compared to the primary human GBM. Tumor tissue analyzed at 24 hours after treatment revealed that IA BV treatment with BBBD led to a significantly higher intratumoral BV concentration compared to IA BV alone, IP BV or controls (p<0.05). Thus, we have developed a TSC-based xenograft mouse model that allows us to study IA chemotherapy. However, further studies are needed to analyze the treatment effects after IA BV to assess tumor progression and overall animal survival. Copyright © 2012 Elsevier Ltd. All rights reserved.

Non-invasive continuous blood pressure monitoring of tachycardic episodes during interventional electrophysiology.

PubMed

Maggi, Roberto; Viscardi, Valentina; Furukawa, Toshiyuki; Brignole, Michele

2010-11-01

We thought to evaluate feasibility of continuous non-invasive blood pressure monitoring during procedures of interventional electrophysiology. We evaluated continuous non-invasive finger blood pressure (BP) monitoring by means of the Nexfin device in 22 patients (mean age 70 ± 24 years), undergoing procedures of interventional electrophysiology, in critical situations of hypotension caused by tachyarrhythmias or by intermittent incremental ventricular temporary pacing till to the maximum tolerated systolic BP fall (mean 61 ± 14 mmHg per patient at a rate of 195 ± 37 bpm). In all patients, Nexfin was able to detect immediately, at the onset of tachyarrythmia, the changes in BP and recorded reliable waveforms. The quality of the signal was arbitrarily classified as excellent in 11 cases, good in 10 cases, and sufficient in 1 case. In basal conditions, calibrations of the signal occurred every 49.2 ± 24.3 s and accounted for 4% of total monitoring time; during tachyarrhythmias their frequency increased to one every 12.7 s and accounted for 19% of total recording duration. A linear correlation for a range of BP values from 41 to 190 mmHg was found between non-invasive and intra-arterial BP among a total of 1055 beats from three patients who underwent simultaneous recordings with both methods (coefficient of correlation of 0.81, P < 0.0001). In conclusion, continuous non-invasive BP monitoring is feasible in the clinical practise of an interventional electrophysiology laboratory without the need of utilization of an intra-arterial BP line.

Beat-to-beat agreement of noninvasive tonometric and intra-radial arterial blood pressure during microgravity and hypergravity generated by parabolic flights.

PubMed

Normand, Hervé; Lemarchand, Erick; Arbeille, Philippe; Quarck, Gaëlle; Vaïda, Pierre; Duretete, Arnaud; Denise, Pierre

2007-12-01

Accurate measurement of beat-to-beat arterial blood pressure is essential for understanding the cardiovascular adaptation to weightlessness; however, the intra-arterial standard of beat-to-beat blood pressure measurement has never been used during space flight because of its invasive nature. The aim of the present study was to compare noninvasive radial artery tonometry blood pressure measurement with intra-radial pressure measurement during microgravity and hypergravity generated by parabolic flights. Two study participants, equipped with an intra-radial pressure line on the left arm and a Colin CBM-7000 (Colin Corp., Komaki City, Japan) beat-to-beat pressure measurement apparatus on the right arm, were studied in a supine position, during parabolic flights on board of the Airbus A300 OG of the Centre National d'Etudes Spatiales. The mean and standard deviations of the beat-to-beat difference between tonometric and intra-radial blood pressure were calculated for systolic and diastolic arterial pressure in the three gravity conditions (1g, 0 g and 1.8 g) experienced during parabolic flight. The Colin CBM-7000 met the specifications required by the Association for the Advancement of Medical Instrumentation in the 0 g environment. Gravity, however, significantly affected the difference between tonometric and intra-arterial blood pressure, possibly owing to the effect of gravity on the apparent weight of the device and the corresponding calibration factor. We conclude that the Colin CBM-7000 can be used with confidence during space flight.

Nociceptive vascular reflexes evoked by scorpion venom modulate cardiorespiratory parameters involving vanilloid receptor 1 in anaesthetised rats.

PubMed

Singh, Sanjeev K; Deshpande, Shripad B

2009-02-27

Involvement of vanilloid and 5-HT(3) receptors in the cardiorespiratory reflexes evoked by intra-arterial (i.a.) injection of Mesobuthus tamulus (BT) venom was examined. In anaesthetised rats, blood pressure, respiratory excursions and ECG were recorded for 60min after the injection of venom in the absence or presence of antagonists. Injection of BT venom (1mg/kg, i.a.) produced alterations in respiratory frequency (RF), blood pressure (BP) and heart rate (HR). The changes in RF were manifested as immediate increase (40%) followed by a decrease (40%) and subsequent sustained increase (60%). In case of BP, the increase began around 40s, peaked at 5min (50%) and remained above the initial level subsequently. The bradycardiac response began around 5min which peaked (50% of the initial) around 25min and remained at that level. Thus, exhibiting immediate-tachypnoeic, intermediate-hypertensive and delayed-bradycardiac responses. Pretreatment with lignocaine, blocked the respiratory responses and attenuated the pressor responses evoked by venom. Pretreatment with capsazepine, vanilloid receptor 1 (VR1) antagonist, antagonized all the three parameters of cardiorespiratory responses evoked by venom. Whereas, ondansetron (5-HT(3) antagonist) attenuated the pressor and bradycardiac responses significantly but not the respiratory responses. These observations indicate that the cardiorespiratory changes induced by intra-arterial injection of venom are carried by afferents in addition to somatic nerves, involving mainly VR1 receptors and partially by 5-HT(3) receptors.

Thromboxane plays a role in postprandial jejunal oxygen uptake and capillary exchange.

PubMed

Alemayehu, A; Chou, C C

1990-09-01

The effects of a thromboxane A2 (TxA2)-endoperoxide receptor antagonist, SQ 29548, on jejunal blood flow, oxygen uptake, and capillary filtration coefficient (Kfc) were determined in anesthetized dogs under resting conditions and during the presence of predigested food in the jejunal lumen in three series of experiments. In series 1, 2.0 micrograms intra-arterial administration of SQ 29548 was found to abolish completely the vasoconstrictor action of graded doses (0.05-2.0 micrograms) of intra-arterial injection of a TxA2-endoperoxide analogue, U44069. SQ 29548 (2.0 micrograms ia) per se did not significantly alter resting jejunal blood flow, oxygen uptake, capillary pressure, or Kfc. Before SQ 29548, placement of food plus bile into the jejunal lumen increased blood flow +42 +/- 9%, oxygen uptake +28 +/- 7%, and Kfc +24 +/- 6%. After SQ 29548, the food placement increased blood flow +37 +/- 8%, oxygen uptake +52 +/- 11%, and Kfc +63 +/- 20%. The food-induced increases in oxygen uptake and Kfc after SQ 29548 were significantly greater than those induced before the blocking of TxA2-endoperoxide receptors by SQ 29548. Our study indicates that endogenous thromboxane does not play a role in regulating jejunal blood flow, capillary filtration, and oxygen uptake under resting conditions. However, it plays a role in limiting the food-induced increases in jejunal oxygen uptake and capillary exchange capacity without influencing the food-induced hyperemia.

Method of cell transplantation promoting the organization of intraarterial thrombus.

PubMed

Hirano, Koji; Shimono, Takatsugu; Imanaka-Yoshida, Kyoko; Miyamoto, Keiichi; Fujinaga, Kazuya; Kajimoto, Masaki; Miyake, Yoichiro; Nishikawa, Masakatsu; Yoshida, Toshimichi; Uchida, Atsumasa; Shimpo, Hideto; Yada, Isao; Hirata, Hitoshi

2005-08-30

Endovascular aortic repairs have been developed as less invasive treatments for aortic aneurysms. Some aneurismal cavities, however, remain without organization, causing a re-expansion of the aneurysms. We studied cell transplantation into the aneurismal sac to promote the organization of thrombus for the complete healing of aneurysms. Skin fibroblasts and skeletal myoblasts were isolated from rats for cell transplantation. An intraarterial thrombus model was made by ligation of the carotid artery. Culture medium (medium group, n=11), collagen gel (gel group, n=11), fibroblasts with collagen gel (F group, n=15), myoblasts with collagen gel (M group, n=12), or mixture of fibroblasts and myoblasts with collagen gel (F+M group, n=14) were injected into the thrombus. After 28 days, histologically, the arterial lumens of the F and M groups were partly filled with fibrous tissues, whereas in the F+M group organization was almost completed and luminal sizes diminished. Immunohistochemical staining demonstrated that alpha-smooth muscle actin-positive cells were more abundantly contained in the organized area of the F+M group than in the other groups. We also analyzed cellular function in vitro with immunofluorescence; coculture of fibroblasts and myoblasts showed that the fraction of alpha-smooth muscle actin-positive fibroblasts increased. This phenomenon accounts for the rapid organization of thrombus in the F+M group in vivo. Cell transplantation accelerated thrombus organization. Especially, myoblasts enhanced differentiation of fibroblasts into myofibroblasts, contributing to rapid thrombus organization. Cell transplantation into unorganized spaces seems applicable to endovascular treatment of aneurysms.

Comparison of the Adsorption of Original and Biosimilar Preparations of Filgrastim on Infusion Sets and the Inhibition of Adsorption by Polysorbate 80.

PubMed

Tange, Mio; Matsumoto, Akino; Yoshida, Miyako; Kojima, Honami; Haraguchi, Tamami; Uchida, Takahiro

2017-01-01

The purpose of the study was to evaluate the adsorption of filgrastim on infusion sets (comprising infusion bag, line and filter) and to compare the adsorption of the original filgrastim preparation with biosimilar preparations using HPLC. The inhibitory effect of polysorbate 80 on this adsorption was also evaluated. Filgrastim was mixed with isotonic sodium chloride solution or 5% (w/v) glucose solution in the infusion fluid. Filgrastim adsorption on infusion sets was observed with all preparations and with both types of infusion solution. The adsorption ratio was about 30% in all circumstances. Filgrastim adsorption on all parts of the infusion set (bag, line and filter) was dramatically decreased by the addition of polysorbate 80 solution at concentrations at or over its critical micelle concentration (CMC). The filgrastim adsorption ratio was highest at a solution pH of 5.65, which is the isoelectric point (pI) of filgrastim. This study showed that the degree of filgrastim adsorption on infusion sets is similar for original and biosimilar preparations, but that the addition of polysorbate 80 to the infusion solution at concentrations at or above its CMC is effective in preventing filgrastim adsorption. The addition of a total-vitamin preparation with a polysorbate 80 concentration over its CMC may be an effective way of preventing filgrastim adsorption on infusion sets.

Sympathetic and cardiovascular responses to venous distension in an occluded limb.

PubMed

Cui, Jian; Leuenberger, Urs A; Gao, Zhaohui; Sinoway, Lawrence I

2011-12-01

We recently showed that a fixed volume (i.e., 40 ml) of saline infused into the venous circulation of an arterially occluded vascular bed increases muscle sympathetic nerve activity (MSNA) and blood pressure. In the present report, we hypothesized that the volume and rate of infusion would influence the magnitude of the sympathetic response. Blood pressure, heart rate, and MSNA were assessed in 13 young healthy subjects during forearm saline infusions (arrested circulation). The effects of different volumes of saline (i.e., 2%, 3%, 4%, or 5% forearm volume at 30 ml/min) and different rates of infusion (i.e., 5% forearm volume at 10, 20, or 30 ml/min) were evaluated. MSNA and blood pressure responses were linked with the infusion volume. Infusion of 5% of forearm volume evoked greater MSNA responses than did infusion of 2% of forearm volume (Δ11.6 ± 1.9 vs. Δ3.1 ± 1.8 bursts/min and Δ332 ± 105 vs. Δ38 ± 32 units/min, all P < 0.05). Moreover, greater MSNA responses were evoked by saline infusion at 30 ml/min than 10 ml/min (P < 0.05). Sonographic measurements confirmed that the saline infusions induced forearm venous distension. The results suggest that volume and rate of saline infusion are important factors in evoking sympathetic activation. We postulate that venous distension contributes to cardiovascular autonomic adjustment in humans.

Rapid-Infusion Rituximab in Lymphoma Treatment: 2-Year Experience in a Single Institution

PubMed Central

Atay, Sevcan; Barista, Ibrahim; Gundogdu, Fatma; Akgedik, Kiymet; Arpaci, Afey

2012-01-01

Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody. We aimed to explore the safety and tolerability of rapid infusion rituximab, (over 90 minutes) in patients with non-Hodgkin's lymphoma at Hacettepe University Department of Medical Oncology. Patients and Methods: Adult patients diagnosed with non-Hodgkin's lymphoma who were to receive rituximab were included in the study. The schedule of administration for cycle 1 was unaltered and delivered according to the product monograph. All subsequent cycles were administered over a total infusion time of 90 minutes (20% of the dose in the first 30 minutes, then the remaining 80% over 60 minutes, total dose delivered in 500 mL). All patients were observed for infusion-related reactions during the rituximab infusion, and vital signs were recorded every 15 minutes. Results: From July 2006 to December 2008, 75 patients with non-Hodgkin's lymphoma were treated with rituximab-based chemotherapy. A total of 372 infusions were administered. The majority of patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, or rituximab only. The 90-minute rituximab infusion schedule was well tolerated, with no grade 3 or 4 infusion-related adverse events observed. Conclusion: A rapid infusion rituximab over 90 minutes is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. PMID:22942806

Growth responses in a mutant dwarf rat to human growth hormone and recombinant human insulin-like growth factor I.

PubMed

Skottner, A; Clark, R G; Fryklund, L; Robinson, I C

1989-05-01

A new mutant GH-deficient dwarf rat has been used to study the effects of iv infusions of human GH (hGH) and recombinant human insulin-like growth factor I (hIGF-I). This animal has only about 5% of normal pituitary GH content, low circulating GH levels, and no regular GH surges. The defect seems to be specific for GH. Infusions of hIGF-I at 180 micrograms/day for 9 days elevated serum IGF-I concentrations significantly over those in the saline-infused controls (713 +/- 20 ng/ml vs. 395 +/- 31 ng/ml); hGH infusions did not raise IGF-I levels significantly (435 +/- 20 ng/ml). Gel filtration of serum samples showed that the high-dose hIGF-I infusions increased free IGF concentrations, without apparently altering the pattern of IGF-I binding whereas hGH infusions increased the amount of high mol wt IGF-I binding protein. Neither IGF-I nor hGH infusions affected the small amounts of rat GH present in the dwarf rat pituitary glands. Continuous iv infusions of hGH (200 mU/day for 9 days) stimulated body wt gain (2.1 +/- 0.2 g/day) and bone growth (96 +/- 9 microns/day) significantly compared to saline-infused dwarf rats (1.2 +/- 0.3 g/day and 43 +/- 3 microns/day). Infusions of hIGF-I at 180 micrograms/day produced a body wt gain (2.1 +/- 0.5 g/day) similar to that seen in the hGH-infused group but a significantly smaller stimulation of bone growth (63 +/- 3 microns/day). Infusion of a 5-fold lower dose of hIGF-I (36 micrograms/day for 9 days) had no effect on body wt or bone growth. Food intake was unaffected by either hGH or hIGF-I infusions. The pattern of tissue growth was affected differentially by hGH and IGF-I infusions that produced the same overall body wt gain. hGH induced a relatively proportional growth in most of the organs studied, whereas hIGF-I infusion at 180 micrograms/day stimulated a disproportionately greater growth of the kidney, adrenals, and spleen. In some of the animals, tissues were extracted for RIA of IGF-I; the amounts of IGF-I in the liver were similar in control, hGH, or IGF-I-infused animals, whereas kidney and adrenals from IGF-I infused animals contained larger amounts of immunoreactive IGF-I than did those tissues from hGH-treated rats. Thus, both hGH and hIGF-I can promote growth in the mutant dwarf rat, but they differ both quantitatively and qualitatively in their pattern of actions.

The effects of intraduodenal nutrient infusion on serum CCK, LES pressure, and gastroesophageal reflux.

PubMed

Lacy, B E; Carter, J; Weiss, J E; Crowell, M D

2011-07-01

Fats cause reflux symptoms in many patients and cholecystokinin (CCK) may play a role. This study was designed to evaluate the effects of intraduodenal nutrient infusion on serum CCK levels, lower esophageal sphincter (LES) pressure, and gastroesophageal reflux (GER). Twenty-four asymptomatic volunteers were studied. A Dent sleeve catheter assessed LES function while an impedance-pH catheter measured reflux events. Participants were randomized to fat (F), carbohydrate (C) or protein (P) infusion. Serum CCK and LES pressures were measured at baseline and after nutrient infusion. Baseline LES pressures and CCK levels were similar in all three groups. A significant linear decrease was found in LES pressure during F, but not C or P, infusion (P=0.004). A significant interaction effect was noted between the infusion groups and CCK levels (P=0.002). A significant linear increase was noted in CCK levels during F but not during C or P infusion (P=0.02). A significant inverse correlation was found between CCK levels and LES pressure (ρ=-0.43; P=0.04). Esophageal acid exposure was significantly increased in the F infusion group (median; interquartile range: 1.10%; 0.25-4.7%) compared to both the C (0.03%; 0.00-0.39%) and P infusion (0.03%; 0.00-0.39%) groups (P=0.04). Intraduodenal F infusion was associated with an increase in CCK levels, while P and C were not. LES pressure decreased significantly after fat infusion and reflux events were more frequent. Fat-induced CCK release is another mechanism that contributes to GER. © 2011 Blackwell Publishing Ltd.

Influence of capsaicin infusion on secondary peristalsis in patients with gastroesophageal reflux disease

PubMed Central

Yi, Chih-Hsun; Lei, Wei-Yi; Hung, Jui-Sheng; Liu, Tso-Tsai; Chen, Chien-Lin; Pace, Fabio

2016-01-01

AIM To determine whether capsaicin infusion could influence heartburn perception and secondary peristalsis in patients with gastroesophageal reflux disease (GERD). METHODS Secondary peristalsis was performed with slow and rapid mid-esophageal injections of air in 10 patients with GERD. In a first protocol, saline and capsaicin-containing red pepper sauce infusions were randomly performed, whereas 2 consecutive sessions of capsaicin-containing red pepper sauce infusions were performed in a second protocol. Tested solutions including 5 mL of red pepper sauce diluted with 15 mL of saline and 20 mL of 0.9% saline were infused into the mid-esophagus via the manometric catheter at a rate of 10 mL/min with a randomized and double-blind fashion. During each study protocol, perception of heartburn, threshold volumes and peristaltic parameters for secondary peristalsis were analyzed and compared between different stimuli. RESULTS Infusion of capsaicin significantly increased heartburn perception in patients with GERD (P < 0.001), whereas repeated capsaicin infusion significantly reduced heartburn perception (P = 0.003). Acute capsaicin infusion decreased threshold volume of secondary peristalsis (P = 0.001) and increased its frequency (P = 0.01) during rapid air injection. The prevalence of GERD patients with successive secondary peristalsis during slow air injection significantly increased after capsaicin infusion (P = 0.001). Repeated capsaicin infusion increased threshold volume of secondary peristalsis (P = 0.002) and reduced the frequency of secondary peristalsis (P = 0.02) during rapid air injection. CONCLUSION Acute esophageal exposure to capsaicin enhances heartburn sensation and promotes secondary peristalsis in gastroesophageal reflux disease, but repetitive capsaicin infusion reverses these effects. PMID:28018112

List of Error-Prone Abbreviations, Symbols, and Dose Designations

MedlinePlus

... unit dose (e.g., diltiazem 125 mg IV infusion “UD” misin- terpreted as meaning to give the entire infusion as a unit [bolus] dose) Use “as directed” ... Names Intended Meaning Misinterpretation Correction “Nitro” drip nitroglycerin infusion Mistaken as sodium nitroprusside infusion Use complete drug ...

Infusion Nursing: An Evidence-Based Approach - Third edition Alexander Mary Infusion Nursing: An Evidence-Based Approach - Third edition 625pp Elsevier 9781416064107 1416064109 [Formula: see text].

PubMed

2010-11-03

This book considers all aspects of infusion therapy and provides a solid evidence base. Its 30 chapters are well organised into six sections covering physiological considerations, infusion therapies and nursing practice.

75 FR 21641 - Infusion Pumps; Public Meeting; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

...] Infusion Pumps; Public Meeting; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION... announcing a public meeting regarding external infusion pumps. The purpose of the meeting is to inform the public about current problems associated with external infusion pump use, to help the agency identify...

21 CFR 880.2420 - Electronic monitor for gravity flow infusion systems.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electronic monitor for gravity flow infusion... and Personal Use Monitoring Devices § 880.2420 Electronic monitor for gravity flow infusion systems. (a) Identification. An electronic monitor for gravity flow infusion systems is a device used to...

21 CFR 880.2420 - Electronic monitor for gravity flow infusion systems.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electronic monitor for gravity flow infusion... and Personal Use Monitoring Devices § 880.2420 Electronic monitor for gravity flow infusion systems. (a) Identification. An electronic monitor for gravity flow infusion systems is a device used to...

21 CFR 880.2420 - Electronic monitor for gravity flow infusion systems.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electronic monitor for gravity flow infusion... and Personal Use Monitoring Devices § 880.2420 Electronic monitor for gravity flow infusion systems. (a) Identification. An electronic monitor for gravity flow infusion systems is a device used to...

21 CFR 880.2420 - Electronic monitor for gravity flow infusion systems.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electronic monitor for gravity flow infusion... and Personal Use Monitoring Devices § 880.2420 Electronic monitor for gravity flow infusion systems. (a) Identification. An electronic monitor for gravity flow infusion systems is a device used to...

21 CFR 880.2420 - Electronic monitor for gravity flow infusion systems.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electronic monitor for gravity flow infusion... and Personal Use Monitoring Devices § 880.2420 Electronic monitor for gravity flow infusion systems. (a) Identification. An electronic monitor for gravity flow infusion systems is a device used to...

Career Education Infused into the Social Studies Curriculum.

ERIC Educational Resources Information Center

Hudson, Patricia; Griggs, Shirley A.

Social studies teachers can help students develop self- and career awareness by infusing career education into the social studies curriculum. The infusion method of career education is preferred since it can make the content of lessons more relevant for students. In addition, infusion of career education is particularly appropriate in social…

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.

Validation of the Hong Kong Liver Cancer Staging System in Determining Prognosis of the North American Patients Following Intra-arterial Therapy

PubMed Central

Sohn, Jae Ho; Duran, Rafael; Zhao, Yan; Fleckenstein, Florian; Chapiro, Julius; Sahu, Sonia P.; Schernthaner, Rüdiger E.; Qian, Tianchen; Lee, Howard; Zhao, Li; Hamilton, James; Frangakis, Constantine; Lin, MingDe; Salem, Riad; Geschwind, Jean-Francois

2018-01-01

Background & Aims There is debate over the best way to stage hepatocellular carcinoma (HCC). We attempted to validate the prognostic and clinical utility of the recently developed Hong Kong Liver Cancer (HKLC) staging system, a hepatitis B-based model, and compared data with that from the Barcelona Clinic Liver Cancer (BCLC) staging system in a North American population who underwent intra-arterial therapy (IAT). Methods We performed a retrospective analysis of data from 1009 patients with HCC who underwent intra-arterial therapy from 2000 through 2014. Most patients had hepatitis C or unresectable tumors; all patients underwent IAT, with or without resection, transplantation, and/or systemic chemotherapy. We calculated HCC stage for each patient using 5-stage HKLC (HKLC-5) and 9-stage HKLC (HKLC-9) system classifications, as well as the BCLC system. Survival information was collected up until end of 2014 at which point living or unconfirmed patients were censored. We compared performance of the BCLC, HKLC-5, and HKLC-9 systems in predicting patient outcomes using Kaplan-Meier estimates, calibration plots, c-statistic, Akaike information criterion, and the likelihood ratio test. Results Median overall survival time, calculated from first IAT until date of death or censorship, for the entire cohort (all stages) was 9.8 months. The BCLC and HKLC staging systems predicted patient survival times with significance (P<.001). HKLC-5 and HKLC-9 each demonstrated good calibration. The HKLC-5 system outperformed the BCLC system in predicting patient survival times (HKLC c=0.71, Akaike information criterion=6242; BCLC c=0.64, Akaike information criterion=6320), reducing error in predicting survival time (HKLC reduced error by 14%, BCLC reduced error by 12%), and homogeneity (HKLC χ2=201; P<.001; BCLC χ2=119; P<.001) and monotonicity (HKLC linear trend χ2=193; P<.001; BCLC linear trend χ2=111; P<.001). Small proportions of patients with HCC of stages IV or V, according to the HKLC system, survived for 6 months and 4 months, respectively. Conclusion In a retrospective analysis of patients who underwent IAT for unresectable HCC, we found the HKLC-5 staging system to have the best combination of performances in survival separation, calibration, and discrimination; it consistently outperformed the BCLC system in predicting survival times of patients. The HKLC system identified patients with HCC of stages IV and V who are unlikely to benefit from IAT. PMID:27847278

Vandetanib-eluting Radiopaque Beads: In vivo Pharmacokinetics, Safety and Toxicity Evaluation following Swine Liver Embolization.

PubMed

Denys, Alban; Czuczman, Peter; Grey, David; Bascal, Zainab; Whomsley, Rhys; Kilpatrick, Hugh; Lewis, Andrew L

2017-01-01

To evaluate the plasma and tissue pharmacokinetics, safety and toxicity following intra-arterial hepatic artery administration of Vandetanib (VTB)-eluting Radiopaque Beads (VERB) in healthy swine. In a first phase, healthy swine were treated with hepatic intra-arterial administration of VERB at target dose loading strengths of 36 mg/mL (VERB36), 72 mg/mL (VERB72) and 120 mg/mL (VERB120). Blood and tissue samples were taken and analysed for VTB and metabolites to determine pharmacokinetic parameters for the different dose forms over 30 days. In a second phase, animals were treated with unloaded radiopaque beads or high dose VTB loaded beads (VERB100, 100 mg/mL). Tissue samples from embolized and non-embolized areas of the liver were evaluated at necropsy (30 and 90 days) for determination of VTB and metabolite levels and tissue pathology. Imaging was performed prior to sacrifice using multi-detector computed tomography (MDCT) and imaging findings correlated with pathological changes in the tissue and location of the radiopaque beads. The peak plasma levels of VTB (C max ) released from the various doses of VERB ranged between 6.19-17.3 ng/mL indicating a low systemic burst release. The plasma profile of VTB was consistent with a distribution phase up to 6 h after administration followed by elimination with a half-life of 20-23 h. The AUC of VTB and its major metabolite N-desmethyl vandetanib (NDM VTB) was approximately linear with the dose strength of VERB. VTB plasma levels were at or below limits of detection two weeks after administration. In liver samples, VTB and NDM VTB were present in treated sections at 30 days after administration at levels above the in vitro IC 50 for biological effectiveness. At 90 days both analytes were still present in treated liver but were near or below the limit of quantification in untreated liver sections, demonstrating sustained release from the VERB. Comparison of the reduction of the liver lobe size and associated tissue changes suggested a more effective embolization with VERB compared to the beads without drug. Hepatic intra-arterial administration of VERB results in a low systemic exposure and enables sustained delivery of VTB to target tissues following embolization. Changes in the liver tissue are consistent with an effective embolization and this study has demonstrated that VERB100 is well tolerated with no obvious systemic toxicity.

Absorption of subcutaneously infused insulin: influence of the basal rate pulse interval.

PubMed

Hildebrandt, P; Birch, K; Jensen, B M; Kühl, C; Brange, J

1985-01-01

Eight insulin-dependent diabetic patients were given two constant infusions (each 1 IU/h) of 125I-labeled insulin into the abdominal subcutaneous tissue for about 12 h. Insulin was infused in pulses into one side of the abdomen in 6-min intervals (by means of an Auto-Syringe pump) and in the other side of the abdomen, insulin was infused in 1-h intervals (by means of a Medix pump). The size of the subcutaneous depots was continuously measured by counting the radioactivity at the infusion sites. After starting the infusions, the two depots were built up to steady-state levels at the same time and of the same size (approximately 3 IU) and with similar absorption rates. Thus, during basal rate insulin infusion, identical insulin absorption kinetics was achieved, irrespective of a 10-fold difference in the pulse rate.

9 CFR 113.28 - Detection of mycoplasma contamination.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REQUIREMENTS Standard Procedures § 113.28 Detection of mycoplasma contamination. The heart infusion test, using heart infusion broth and heart infusion agar, provided in this section shall be conducted when a test... inactivated at 56 °C for 30 minutes. (b) Heart infusion broth shall be prepared as provided in this paragraph...

75 FR 12760 - Determination That CERNEVIT-12 (Multivitamins for Infusion) Was Withdrawn From Sale for Reasons...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-17

...] Determination That CERNEVIT-12 (Multivitamins for Infusion) Was Withdrawn From Sale for Reasons of Safety or...) has determined that CERNEVIT-12, multivitamins for infusion (retinol palmitate corresponding to... (multivitamins for infusion)), was withdrawn from sale for reasons of safety or effectiveness. FDA therefore will...

Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: potential for group housing.

PubMed

Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Mårtensson, Martin; Strid, Mette Aagaard; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

2017-06-01

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin analogues. Human insulin (HI) is frequently used as a reference compound in these studies, and a comparator model of persistent exposure by HI infusion from external pumps has recently been developed to support toxicological evaluation of long-acting insulin analogues. However, this model requires single housing of the animals. Developing an insulin-infusion model which allows group housing would therefore greatly improve animal welfare. The aim of the present study was to investigate the suitability of implantable infusion pumps for HI infusion in group-housed rats. Group housing of rats implanted with a battery-driven pump proved to be possible. Intravenous infusion of HI lowered blood glucose levels persistently for two weeks, providing a comparator model for use in two-week repeated-dose toxicity studies with new long-acting insulin analogues, which allows group housing, and thereby increasing animal welfare compared with an external infusion model.

Home-based infusion therapy for patients with Fabry disease.

PubMed

Cousins, A; Lee, P; Rorman, D; Raas-Rothschild, A; Banikazemi, M; Waldek, S; Thompson, L

Fabry disease is an inherited, progressive, life-threatening disease; therefore, lifelong therapy is needed. By replacing the deficient enzyme, disease progression may be delayed or halted, thereby avoiding serious complications. Hospital-based agalsidase therapy is generally perceived as inconvenient and home-based infusion therapy is greatly appreciated by patients, their families and healthcare professionals. Patients can get familiar with infusion therapy in a hospital setting and, if specific requirements are fulfilled, routine nurse-assisted infusion, or self-care, at the patient's home can be organized. A stable patient who tolerates the infusion and a suitable home environment are prerequisites for home therapy. The authors' clinical experiences underscore the safety and practicality of home therapy. In addition to a major positive impact on the patient's quality of life, home infusion therapy may reduce the constraints of hospital resources. This article reviews the collective experiences with agalsidase beta home infusion therapy and outlines how safe, patient-centred homecare can be organized. Home infusion therapy with Fabrazyme should not be withheld from patients considered eligible according to the proposed criteria. Similar approaches to other enzyme therapies are also possible.

Mechanism of delayed intracranial hypertension after cerebroventricular infusions in conscious rats

NASA Technical Reports Server (NTRS)

Morrow, B. A.; Holt, M. R.; Starcevic, V. P.; Keil, L. C.; Severs, W. B.

1992-01-01

Prior studies showed that cerebroventricular infusions of artificial cerebrospinal fluid, 8 microliter/min for 10 min, followed by a 10 min rest and a 24 h infusion of 0.5 microliters/min, raised cerebrospinal fluid pressure (CSFp) of conscious, unrestrained rats after about 2 h. Here, we report that the 10 min infusion alone evoked a delayed, prolonged rise in CSFp. Pressure during the infusion itself rose and recovered quickly, as is usually reported. Pressure/volume tests, used to calculate resistance to outflow (Ro) and compliance (C), revealed that infusions increased Ro and decreased C, after a delay (P less than 0.05). The rise in CSFp after infusion was blocked by pretreatment with acetazolamide + ouabain (P less than 0.05), but the delayed changes in Ro and C were unaffected. We suggest that the 10 min infusion of a sterile, balanced salt solution has a primary effect that increases Ro; as CSF synthesis continues, C is exhausted and the delayed rise in CSFp ensues. This non-traumatic method of raising CSFp may be a useful method to study intracranial fluid dynamics.

The effect of tubing dwell time on insulin adsorption during intravenous insulin infusions.

PubMed

Thompson, Cecilia D; Vital-Carona, Jessica; Faustino, E Vincent S

2012-10-01

Insulin adsorbs to plastic tubing, which decreases the concentration of an insulin solution delivered from an intravenous infusion set. Dwelling insulin within tubing before starting the infusion decreases adsorption but delays treatment initiation and wastes time in infusion preparation. The lack of data on dwell time effects results in wide variability in practice. We aim to determine the effect of dwell time on insulin concentration from intravenous infusion tubing. In this in vitro study, we used insulin solutions with concentrations of 0.1 unit/mL, 1 unit/mL, and 10 units/mL. Each solution dwelled in intravenous infusion sets for 0, 15, 30, or 60 min. After the dwell, we measured insulin concentrations from the solution bags and tubing. We repeated each insulin concentration-dwell time combination five times. Comparisons were performed using analyses of variance. For each of the three insulin concentrations, the mean insulin concentrations from the tubing were not significantly different between dwell times. Duration of dwell time did not affect insulin adsorption in polypropylene intravenous infusion sets. We recommend that following a 20-mL flush, insulin infusions can be started without any dwell time. Removal of dwell times may improve clinical practice by minimizing preparation time and will allow faster initiation of insulin infusion therapy.

Antioxidant and antimicrobial properties of Teucrium arduini L. (Lamiaceae) flower and leaf infusions (Teucrium arduini L. antioxidant capacity).

PubMed

Samec, D; Gruz, J; Strnad, M; Kremer, D; Kosalec, I; Grubesić, R Jurisić; Karlović, K; Lucic, A; Piljac-Zegarac, J

2010-01-01

Antioxidant and antimicrobial activities, as well as total phenol (TP, Folin-Ciocalteu method) and phenolic acid (UPLC-MS/MS) contents of leaf and flower infusions of Teucrium arduini L. from six different mountainous localities in Croatia (Ucka, Vosac, Sveti Jure, Snjeznica, Vaganac, Susanj) were analysed in this study. Antioxidant capacity was evaluated using the ferric reducing/antioxidant power (FRAP) assay, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging assays. The antioxidant potency composite index (ACI), giving equal weight to all three methods used to quantify antioxidant capacity, was the highest for the sample from Vosac (96.7) among flower infusions, while maximum ACI (100) was determined for the infusion from Ucka among leaf infusions. Strong positive correlation was found between the total phenols and ACI for leaf (r=0.953) and flower (r=0.977) infusions. Our results point to significantly (p<0.05) different TP content between leaf and flower infusions, as well as across localities. Leaf infusions of T. arduini from Susanj exhibited marked antibacterial activity against Staphylococcus aureus, while none of the tested infusions exhibited antimicrobial activity against gram-negative bacterial species, or the tested fungal species. Copyright 2009 Elsevier Ltd. All rights reserved.

Pantoprazole before Endoscopy in Patients with Gastroduodenal Ulcer Bleeding: Does the duration of Infusion and Ulcer Location Influence the Effects?

PubMed Central

Rácz, Istvan; Szalai, Milan; Dancs, Nora; Kárász, Tibor; Szabó, Andrea; Csöndes, Mihaly; Horváth, Zoltan

2012-01-01

The aim of this study was to investigate the effect of preemptive pantoprazole infusion on early endoscopic findings in patients with acute ulcer bleeding. Records of 333 patients admitted with acute ulcer bleeding were analyzed. Ulcer bleeders were given either 80 mg bolus of pantoprazole followed by continuous infusion of 8 mg per hour or saline infusion until endoscopy. In 93 patients saline infusion whereas in 240 patients bolus plus infusion of pantoprazole was administrated with mean (±SD) durations of 5.45 ± 12.9 hours and 6.9 ± 13.2 hours, respectively (P = 0.29). Actively bleeding ulcers were detected in 46/240 (19.2%) of cases in the pantoprazole group as compared with 23/93 (24.7%) in the saline infusion group (P = 0.26). Different durations of pantoprazole infusion (0–4 hours, >4 hours, and >6 hours) had no significant effect on endoscopic and clinical outcome parameters in duodenal ulcer bleeders. Gastric ulcer bleeders on pantoprazole infusion longer than 4 and 6 hours before endoscopy had actively bleeding ulcers in 4.3% and 5% compared to the 19.5% active bleeding rate in the saline group (P = 0.02 and P = 0.04). Preemptive infusion of high-dose pantoprazole longer than 4 hours before endoscopy decreased the ratio of active bleeding only in gastric but not in duodenal ulcer patients. PMID:23125849

High-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections in immunocompromised patients.

PubMed

Moriyama, Brad; Henning, Stacey A; Childs, Richard; Holland, Steven M; Anderson, Victoria L; Morris, John C; Wilson, Wyndham H; Drusano, George L; Walsh, Thomas J

2010-05-01

To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. Continuous infusion ceftazidime or aztreonam was administered to achieve target drug concentrations at or above the minimum inhibitory concentration, when possible, in 3 patients with P. aeruginosa infections. The maximal calculated target drug concentration was 100 mg/L. In the first patient, with primary immunodeficiency, neutropenia, and aggressive cutaneous T-cell lymphoma/leukemia, continuous infusion ceftazidime (6.5-9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient, with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient, with severe aplastic anemia, continuous infusion ceftazidime (7-16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy, when no other options are available, is the continuous infusion of existing beta-lactam antibiotics to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in 3 chronically immunocompromised patients. Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients.

Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

PubMed

Schmier, Jordana; Ogden, Kristine; Nickman, Nancy; Halpern, Michael T; Cifaldi, Mary; Ganguli, Arijit; Bao, Yanjun; Garg, Vishvas

2017-08-01

Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Influence of technique used to attach the infusion set to peristaltic finger smart-pumps on dispensing time: an experimental study.

PubMed

Umemura, Masayuki; Maegawa, Kanae; Arai, Daichi; Shigeno, Katsuro; Wakiya, Yoshifumi

2018-01-01

Infusion sets designed for peristaltic finger smart pumps (PFSPs) are necessary for the pumps' accurate handling. We previously found that medication dispensing is occasionally incomplete following the calculated infusion time when using certain combinations of PFSPs and infusion sets at a Japanese hospital. Thus, in this study, we investigated the cause of this observed delay by determining the effect of infusion set attachment technique on dispensing time using a combination of three kinds of PFSPs and five kinds of polyvinyl chloride (PVC) and polybutadiene (PB) infusion sets. PFSPs with their exclusive infusion sets were used. The PVC and PB infusion sets were either not stretched or stretched to 1-3 cm and attached to the PFSP's liquid delivery system. PFSP dispensing rates were set at 25-400 mL/h. The primary outcome was the time required to dispense 100 mL of saline in a volumetric flask. The complete dispensing time correlated with the input time for all equipment combinations when the infusion sets were not stretched before attachment to the PFSP (R 2  = 0.9998-1.0000). When stretched, the complete dispensing time was longer than the input time ( P  < 0.01-0.05, analysis of variance with Tukey-Kramer multiple comparisons). The maximum dispensing time extension ratio for the PVC and PB infusion sets was 141.8% and 113.0%, respectively. Certain attachment techniques for infusion sets can adversely prolong drug dispensing time. As such, pharmacists should provide medical staff with information about the devices used to administer drugs, as well as about the drugs themselves.

Outcomes of an extended-infusion piperacillin-tazobactam protocol implementation in a community teaching hospital adult intensive care unit.

PubMed

Schmees, Patrick M; Bergman, Scott J; Strader, Brandi D; Metzke, Megan E; Pointer, Sarah; Valenti, Kristine M

2016-06-01

The purpose of this study is to evaluate the outcome differences between patients receiving piperacillin-tazobactam pre- and post-implementation of an extended infusion dosing protocol in a community teaching hospital adult intensive care unit. On December 19th, 2011, extended infusion dosing of piperacillin-tazobactam was implemented at St. John's Hospital's intensive and cardiac care units (ICU/CCU) following IRB-approval. This is a historical case-control cohort study involving review of electronic medical charts of patients who received traditional or extended infusion therapy. Data was collected for patients that received piperacillin-tazobactam in the ICU/CCU from December 19th, 2010 through March 19th, 2011 for traditional infusion and from December 19th, 2011 through March 19th, 2012 for extended infusion. Primary endpoints were ICU/CCU mortality at discharge and length of stay. The study included 113 patients with 52 in the traditional-infusion group and 61 extended-infusion group. There was no statistically significant difference in the primary end-point of ICU/CCU mortality between the two groups (14.8% vs. 21.1%; p = 0.374). In the extended infusion group, there was a shorter length of ICU and CCU stay (8.32 vs. 12.06 days; p = 0.025) and shorter length of hospital stay (11.32 vs. 19.7 days; p = 0.006). The extended-infusion group showed a decrease in cost of therapy that was statistically significant ($120.21 vs. $155.17; p = 0.035). Adverse drug effects did not differ between the two study groups. This study showed that treatment with extended-infusion piperacillin-tazobactam therapy improved patient outcomes while maintaining patient safety and decreasing costs. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

PubMed

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

[Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

PubMed

Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

2016-01-01

To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Multiple Intravenous Infusions Phase 2b: Laboratory Study

PubMed Central

Pinkney, Sonia; Fan, Mark; Chan, Katherine; Koczmara, Christine; Colvin, Christopher; Sasangohar, Farzan; Masino, Caterina; Easty, Anthony; Trbovich, Patricia

2014-01-01

Background Administering multiple intravenous (IV) infusions to a single patient via infusion pump occurs routinely in health care, but there has been little empirical research examining the risks associated with this practice or ways to mitigate those risks. Objectives To identify the risks associated with multiple IV infusions and assess the impact of interventions on nurses’ ability to safely administer them. Data Sources and Review Methods Forty nurses completed infusion-related tasks in a simulated adult intensive care unit, with and without interventions (i.e., repeated-measures design). Results Errors were observed in completing common tasks associated with the administration of multiple IV infusions, including the following (all values from baseline, which was current practice): setting up and programming multiple primary continuous IV infusions (e.g., 11.7% programming errors) identifying IV infusions (e.g., 7.7% line-tracing errors) managing dead volume (e.g., 96.0% flush rate errors following IV syringe dose administration) setting up a secondary intermittent IV infusion (e.g., 11.3% secondary clamp errors) administering an IV pump bolus (e.g., 11.5% programming errors) Of 10 interventions tested, 6 (1 practice, 3 technology, and 2 educational) significantly decreased or even eliminated errors compared to baseline. Limitations The simulation of an adult intensive care unit at 1 hospital limited the ability to generalize results. The study results were representative of nurses who received training in the interventions but had little experience using them. The longitudinal effects of the interventions were not studied. Conclusions Administering and managing multiple IV infusions is a complex and risk-prone activity. However, when a patient requires multiple IV infusions, targeted interventions can reduce identified risks. A combination of standardized practice, technology improvements, and targeted education is required. PMID:26316919

Randomized Trial of Infusion Set Function: Steel Versus Teflon

PubMed Central

Patel, Parul J.; Benasi, Kari; Ferrari, Gina; Evans, Mark G.; Shanmugham, Satya; Wilson, Darrell M.

2014-01-01

Abstract Background: This study compared infusion set function for up to 1 week using either a Teflon® (Dupont™, Wilmington, DE) catheter or a steel catheter for insulin pump therapy in type 1 diabetes mellitus. Subjects and Methods: Twenty subjects participating in a randomized, open-labeled, crossover study were asked to wear two Quick-Set® and two Sure-T® infusion sets (both from Medtronic Minimed, Northridge, CA) until the infusion set failed or was worn for 1 week. All subjects wore a MiniMed continuous glucose monitoring system for the duration of the study. Results: One subject withdrew from the study. There were 38 weeks of Sure-T wear and 39 weeks of Quick-Set wear with no difference in the survival curves of the infusion sets. There was, however, a 15% initial failure rate with the Teflon infusion set. After 7 days, both types of infusion sets had a 64% failure rate. Overall, 30% failed because of hyperglycemia and a failed correction dose, 13% were removed for pain, 10% were pulled out by accident, 10% had erythema and/or induration of>10 mm, 5% fell out because of loss of adhesion, and 4% were removed for infection. The main predictor of length of wear was the individual subject. There was no increase in hyperglycemia or daily insulin requirements when an infusion set was successfully used for 7 days (n=25 of 77 weeks). Conclusions: We found no difference between steel and Teflon infusion sets in their function over 7 days, although 15% of Teflon sets failed because of kinking on insertion. The strongest predictor of prolonged 7-day infusion set function was the individual subject, not the type of infusion set. PMID:24090124

Multiple Intravenous Infusions Phase 2a: Ontario Survey

PubMed Central

Fan, Mark; Koczmara, Christine; Masino, Caterina; Cassano-Piché, Andrea; Trbovich, Patricia; Easty, Anthony

2014-01-01

Background Research conducted in earlier phases of this study prospectively identified a number of concerns related to the safe administration of multiple intravenous (IV) infusions in Ontario hospitals. Objective To investigate the potential prevalence of practices or policies that may contribute to the patient safety risks identified in Phase 1b of this study. Data Sources and Review Methods Sixty-four survey responses were analyzed from clinical units where multiple IV infusions may occur (e.g., adult intensive care units). Survey questions were organized according to the topics identified in Phase 1b as potential contributors to patient harm (e.g., labelling practices, patient transfer practices, secondary infusion policies). Results Survey results indicated suboptimal practices and policies in some clinical units, and variability in a number of infusion practices. Key areas of concern included the following: use of primary IV tubing without back check valves when administering secondary infusions administration of secondary infusions with/as high-alert continuous IV medications potential confusion about how IV tubing should be labelled to reflect replacement date and time interruptions to IV therapy due to IV pump and/or tubing changes when patients are transferred between clinical units coadministration of continuous or intermittent infusions on central venous pressure monitoring ports variability in respondents’ awareness of the infusion pump's bolus capabilities Limitations Due to the limited sample size, survey responses may not be representative of infusion practices across Ontario. Answers to some questions indicated that the intent of the questions might have been misunderstood. Due to a design error, 1 question about bolus administration methods was not shown to as many respondents as appropriate. Conclusions The Ontario survey revealed variability in IV infusion practice across the province and potential opportunities to improve safety. PMID:26257837

Evaluation of drug-metabolizing and functional competence of human hepatocytes incubated under hypothermia in different media for clinical infusion.

PubMed

Gómez-Lechón, María José; Lahoz, Agustín; Jiménez, Nuria; Bonora, Ana; Castell, José V; Donato, María Teresa

2008-01-01

Hepatocyte transplantation has been proposed as a method to support patients with liver insufficiency. Key factors for clinical cell transplantation to progress is to prevent hepatocyte damage, loss of viability and cell functionality, factors that depend on the nature of the tissue used for isolation to a large extent. The main sources of tissue for hepatocyte isolation are marginal livers that are unsuitable for transplantation, and segments from reduced cadaveric grafts. Hepatocellular transplantation requires infusing human hepatocytes in suspension over a period of minutes to hours. The beneficial effect of hypothermic preservation of hepatocytes in infusion medium has been reported, but how critical issues towards the success of cell transplantation, such as the composition of infusion medium and duration of hepatocyte storage will affect hepatocyte quality for clinical cell infusion has not been systematically investigated. Infusion media composition is phosphate-buffered saline containing anticoagulants and human serum albumin. The supplementation of infusion media with glucose or N-acetyl-cystein, or with both components at the same time, has been investigated. After isolation, hepatocytes were suspended in each infusion medium and a sample at the 0 time point was harvested for cell viability and functional assessment. Thereafter, cells were incubated in different infusion media agitated on a rocker platform to simulate the clinical infusion technique. The time course of hepatocyte viability, funtionality (drug-metabolizing enzymes, ureogenic capability, ATP, glycogen, and GSH levels), apoptosis (caspase-3 activation), and attachment and monolayer formation were analyzed. The optimal preservation of cell viability, attaching capacity, and functionality, particularly GSH and glycogen levels, as well as drug-metabolizing cytochrome P450 enzymes, was found in infusion media supplemented with 2 mM N-acetyl-cystein and 15 mM glucose.

Alarm Limits for Intraoperative Drug Infusions: A Report From the Multicenter Perioperative Outcomes Group.

PubMed

Berman, Mitchell F; Iyer, Nikhil; Freudzon, Leon; Wang, Shuang; Freundlich, Robert E; Housey, Michelle; Kheterpal, Sachin

2017-10-01

Continuous medication infusions are commonly used during surgical procedures. Alarm settings for infusion pumps are considered important for patient safety, but limits are not created in a standardized manner from actual usage data. We estimated 90th and 95th percentile infusion rates from a national database for potential use as upper limit alarm settings. We extracted infusion rate data from 17 major hospitals using intraoperative records provided by Multicenter Perioperative Outcomes Group for adult surgery between 2008 and 2014. Seven infusions were selected for study: propofol, remifentanil, dexmedetomidine, norepinephrine, phenylephrine, nitroglycerin, and esmolol. Each dosage entry for an infusion during a procedure was included. We estimated the 50th, 90th, and 95th percentile levels for each infusion across institutions, and performed quantile regression to examine factors that might affect the percentiles rates, such as use in general anesthesia versus sedation. The median 90th and 95th percentile infusion rates (with interquartile range) for propofol were 150 (140-150) and 170 (150-200) μg/kg/min. Quantile regression demonstrated higher 90th and 95th percentile rates during sedation for gastrointestinal endoscopy than for all surgical procedures performed under general anesthesia. For selected vasoactive medications, the corresponding median 90th and 95th percentile rates (with interquartile range) were norepinephrine 14.0 (9.8-18.1) and 18.3 (12.6-23.9) μg/min, and phenylephrine 60 (55-80) and 80 (75-100) μg/min. Alarm settings based on infusion rate percentile limits would be triggered at predictable rates; ie, the 95th percentile would be exceeded and an alarm sounded during 1 in 20 infusion rate entries. As a result, institutions could establish pump alarm settings consistent with desired alarm frequency using their own or externally validated usage data. Further study will be needed to determine the optimal percentile for infusion alarm settings.

Dose-response characteristics of intravenous ketamine on dissociative stereotypy, locomotion, sensorimotor gating, and nociception in male Sprague-Dawley rats.

PubMed

Radford, Kennett D; Park, Thomas Y; Lee, Bong Hyo; Moran, Sean; Osborne, Lisa A; Choi, Kwang H

2017-02-01

Clinicians administer subanesthetic intravenous (IV) ketamine infusions for treatment of refractory depression, chronic pain, and post-traumatic stress disorder in humans. However, ketamine is administered via the subcutaneous (SC) or intraperitoneal (IP) routes to rodents in most pre-clinical research, which may limit translational application. The present study characterized the dose-response of a subanesthetic IV ketamine bolus (2 and 5mg/kg) and 1-h infusion (5, 10, and 20mg/kg/h) on dissociative stereotypy, locomotion, sensorimotor gating, and thermal nociception in male Sprague-Dawley rats. The secondary aim was to measure ketamine and norketamine plasma concentrations following IV ketamine bolus at 1, 20, and 50min and at the conclusion of the 1-h infusion using liquid chromatography/mass spectrometry. The results showed that ketamine bolus and infusions produced dose-dependent dissociative stereotypy. Bolus (2 and 5mg/kg) and 20mg/kg/h infusion increased locomotor activity while 5mg/kg/h infusion decreased locomotor activity. Both 10 and 20mg/kg/h infusions reduced the acoustic startle reflex, while 5mg/kg bolus and 20mg/kg/h infusion impaired pre-pulse inhibition. Ketamine 5mg/kg bolus and the 10 and 20mg/kg/h infusions induced significant and prolonged antinociception to the hotplate test. Plasma concentrations of ketamine decreased quickly after bolus while norketamine levels increased from 1 to 20min and plateaued from 20 to 50min. The peak ketamine plasma concentrations [ng/ml] were similar between 5mg/kg bolus [4100] vs. 20mg/kg/h infusion [3900], and 2mg/kg bolus [1700] vs. 10mg/kg/h infusion [1500]. These results support the findings from previous ketamine injection studies and further validate the feasibility of administering subanesthetic doses of IV ketamine infusion to rats for neuropharmacological studies. Published by Elsevier Inc.

Image-guided convection-enhanced delivery of muscimol to the primate brain

PubMed Central

Heiss, John D.; Walbridge, Stuart; Asthagiri, Ashok R.; Lonser, Russell R.

2009-01-01

Object Muscimol is a potent γ-aminobutyric acid-A receptor agonist (GABAA) that temporarily and selectively suppresses neurons. Targeted muscimol-suppression of neuronal structures could provide insight into the pathophysiology and treatment of a variety of neurologic disorders. To determine if muscimol delivered to the brain by convection-enhanced delivery (CED) could be monitored using a co-infused surrogate magnetic resonance (MR)-imaging tracer, we perfused the striata of primates with tritiated muscimol and gadolinium-DTPA. Methods Three primates underwent convective co-infusion of 3H-muscimol (0.8 μM) and gadolinium-DTPA (−5 mM) into the bilateral striata. Primates underwent serial MR-imaging during infusion and animals were sacrificed immediately after infusion. Post-mortem quantitative autoradiography and histological analysis was performed. Results MR-imaging revealed that infusate (tritiated muscimol and gadolinium-DTPA) distribution was clearly discernible from the non-infused parenchyma. Real-time MR-imaging of the infusion revealed the precise region of anatomic perfusion in each animal. Imaging analysis during infusion revealed that the distribution volume of infusate linearly increased (R=0.92) with volume of infusion. Overall, the mean (±S.D.) volume of distribution to volume of infusion ratio was 8.2±1.3. Autoradiographic analysis revealed that MR-imaging of gadolinium-DTPA closely correlated with the distribution of 3H-muscimol and precisely estimated its volume of distribution (mean difference in volume of distribution, 7.4%). Quantitative autoradiograms revealed that muscimol was homogeneously distributed over the perfused region in a square-shaped concentration profile. Conclusions Muscimol can be effectively delivered to clinically relevant volumes of the primate brain. Moreover, the distribution of muscimol can be tracked by co-infusion of gadolinium-DTPA using MR-imaging. The ability to accurately monitor and control the anatomic extent of muscimol distribution during its convection-enhanced delivery will enhance safety, permit correlations of muscimol distribution with clinical effect, and should lead to an improved understanding of the pathophysiologic processes underlying a variety of neurologic disorders. PMID:19715424

Infusion of adrenergic receptor agonists and antagonists into the locus coeruleus and ventricular system of the brain. Effects on swim-motivated and spontaneous motor activity.

PubMed

Weiss, J M; Simson, P G; Hoffman, L J; Ambrose, M J; Cooper, S; Webster, A

1986-04-01

These studies examined how pharmacological stimulation and blockade of alpha receptors would affect active motor behavior in rats. In experiment I, alpha-2 receptor antagonists (piperoxane, yohimbine) and agonists [clonidine, norepinephrine (NE)] were infused into various locations in the ventricular system of the brain, including the locus coeruleus region, and motor activity was measured. Activity was measured principally in a swim test but spontaneous (ambulatory) activity was also recorded while drugs were being infused. When infused into the locus coeruleus region, small doses of the antagonists piperoxane and yohimbine depressed activity in the swim test while infusion of the agonists clonidine and NE had the opposite effect of stimulating activity. These effects were highly specific to the region of the locus coeruleus, since infusions of these drugs into other nearby locations in the ventricular system or use of larger doses had different, often opposite effects. This was especially true of clonidine and NE which profoundly depressed activity when infused posterior to the locus coeruleus, particularly over the dorsal vagal complex. Infusion of small doses of these drugs into the lateral ventricle had effects similar to infusion into the locus coeruleus region, though less pronounced. Changes in spontaneous motor activity were also observed, but this measure differentiated the groups less well than did the swim test. In experiment II, the predominantly postsynaptic receptor agonists isoproterenol (beta agonist) and phenylephrine (alpha-1 agonist) were infused into the ventricular system. Since infusions of piperoxane and yohimbine into the locus coeruleus that decreased activity in experiment I increase the release of NE by blocking alpha-2 inhibitory receptors on cell bodies and dendrites of the locus coeruleus, experiment II tested whether ventricular infusion of predominantly postsynaptic receptor agonists would also decrease activity in the swim test. Both isoproterenol and phenylephrine produced this effect, but did so selectively with respect to dose and location of infusion in the ventricular system. These findings are consistent with recent results relating to the mechanism that underlies stress-induced depression of active behavior.

[Cerebral protection].

PubMed

Cattaneo, A D

1993-09-01

Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral metabolic standpoint, exposure to isoflurane at concentration of 2 MAC is credited with providing the same potential for protection as high dose barbiturate (isoelectric EEG). A possible major difference between barbiturates and isoflurane is the modest cerebral vasodilation induced by the latter while barbiturates are associated with decreased CBF. This suggests that in focal ischemia isoflurane may elicit an intracerebral steal. 3) Calcium entry blockers. Some calcium entry blockers with the distinctive feature of acting preferably on cerebral as opposed to systemic vascular smooth muscles may exert beneficial effects during or after brain ischemia. Two such drugs which have shown promise are nimodipine and lidoflazine. In animal and human studies nimodipine has been reported to improve the neurologic outcome of both the cerebral vasospasm and the postischemic hypoperfusion state.(ABSTRACT TRUNCATED AT 400 WORDS)

Types and Frequency of Infusion Pump Alarms: Protocol for a Retrospective Data Analysis.

PubMed

Glover, Kevin R; Vitoux, Rachel R; Schuster, Catherine; Curtin, Christopher R

2018-06-14

The variety of alarms from all types of medical devices has increased from 6 to 40 in the last three decades, with today's most critically ill patients experiencing as many as 45 alarms per hour. Alarm fatigue has been identified as a critical safety issue for clinical staff that can lead to potentially dangerous delays or nonresponse to actionable alarms, resulting in serious patient injury and death. To date, most research on medical device alarms has focused on the nonactionable alarms of physiological monitoring devices. While there have been some reports in the literature related to drug library alerts during the infusion pump programing sequence, research related to the types and frequencies of actionable infusion pump alarms remains largely unexplored. The objectives of this study protocol are to establish baseline data related to the types and frequency of infusion pump alarms from the B. Braun Outlook 400ES Safety Infusion System with the accompanying DoseTrac Infusion Management Software. The most recent consecutive 60-day period of backup hospital data received between April 2014 and February 2017 from 32 United States-based hospitals will be selected for analysis. Microsoft SQL Server (2012 - 11.0.5343.0 X64) will be used to manage the data with unique code written to sort data and perform descriptive analyses. A validated data management methodology will be utilized to clean and analyze the data. Data management procedures will include blinding, cleaning, and review of existing infusion data within the DoseTrac Infusion Management Software databases at each hospital. Patient-identifying data will be removed prior to merging into a dedicated and secure data repository. This pooled data will then be analyzed. This exploratory study will analyze the aggregate alarm data for each hospital by care area, drug infused, time of day, and day of week, including: overall infusion pump alarm frequency (number of alarms per active infusion), duration of alarms (average, range, median), and type and frequency of alarms distributed by care area. Infusion pump alarm data collected and analyzed in this study will be used to help establish a baseline of infusion pump alarm types and relative frequencies. Understanding the incidences and characteristics of infusion pump alarms will result in more informed quality improvement recommendations to decrease and/or modify infusion pump alarms, and potentially reduce clinical staff alarm fatigue and improve patient safety. . RR1-10.2196/10446. ©Kevin R Glover, Rachel R Vitoux, Catherine Schuster, Christopher R Curtin. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 14.06.2018.

Continuous-Infusion Antipseudomonal Beta-Lactam Therapy in Patients With Cystic Fibrosis

PubMed Central

Prescott, William A.; Gentile, Allison E.; Nagel, Jerod L.; Pettit, Rebecca S.

2011-01-01

Objective: We sought to evaluate the pharmacokinetics, efficacy, safety, stability, pharmacoeconomics, and quality-of-life effects of continuous-infusion antipseudomonal beta-lactam therapy in patients with cystic fibrosis (CF). Data Sources: Literature retrieval was accessed through Medline (from 1950 to December 2010) using the following terms: cystic fibrosis; beta-lactams or piperacillin or ticarcillin or cefepime or ceftazidime or doripenem or meropenem or imipenem/cilastin or aztreonam; continuous infusion or constant infusion; drug stability; economics, pharmaceutical; and quality of life. In addition, reference citations from identified publications were reviewed. Study Selection and Data Extraction: We evaluated all articles in English identified from the data sources. Data Synthesis: Patients with CF often harbor colonies of multidrug-resistant organisms, increasing the risk of suboptimal dosing and failure to meet the time above the minimum inhibitory concentration (T > MIC) pharmacodynamic targets. The pharmacokinetics of continuous-infusion antipseudomonal beta-lactam therapy in CF maintains serum concentrations above the MIC of susceptible strains and is more likely than intermittent infusion to achieve optimal T > MIC targets for some intermediate and resistant strains of Pseudomonas aeruginosa. Three noncomparative and four comparative studies have assessed the efficacy and safety of continuous-infusion antipseudomonal beta-lactam therapy during CF pulmonary exacerbations. Ceftazidime, the most extensively studied antibiotic for continuous infusion in CF, has been shown to improve forced expiratory volume in 1 second (FEV1), to improve forced vital capacity (FVC), and to extend the time between pulmonary exacerbations. Continuous-infusion cefepime has been studied in a small number of patients, and a trend toward improved pulmonary function has been observed. Continuous-infusion antipseudomonal beta-lactam therapy appears to be well tolerated, although most of the data pertain to ceftazidime. Because continuous infusion may necessitate that patients wear a portable pump in close proximity to the body, the stability of the antibiotic at body temperature must be considered. Several beta-lactams have good stability at body temperature (piperacillin/tazobactam, ticarcillin/clavulanate, and aztreonam) or acceptable if the medication cartridge is changed twice daily (cefepime and doripenem), whereas other beta-lactams have acceptable 24-hour stability only at lower temperatures (cefepime, ceftazidime, doripenem, and meropenem). Although no pharmacoeconomic studies have evaluated the cost–benefit of continuous infusion versus intermittent infusion in patients with CF, the potential medication cost reduction appears to be considerable. There is little information regarding the impact of continuous infusion on quality of life in patients with CF. Conclusion: Efficacy and safety studies suggest that ceftazidime, administered as a continuous infusion for the treatment of CF pulmonary exacerbations, is safe and effective; has the potential to reduce the costs of treatment; and is preferred to intermittent infusion among patients treated at home. Continuous-infusion ceftazidime may therefore be an alternative to traditional dosing on a case-by-case basis, such as for patients with multidrug-resistant isolates of P. aeruginosa. Treatment with continuous-infusion ceftazidime at home may be considered in such a case, assuming resources and support equivalent to the hospital setting can be ensured. Additional studies assessing the safety and efficacy of other antipseudomonal beta-lactams, when administered as a continuous infusion, during CF pulmonary exacerbations are needed. PMID:22346306

76 FR 8637 - Medical Devices; Medical Device Data Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-15

... would alter the parameters on an infusion pump. The MDDS could pass that control signal to the infusion... proposed Sec. 880.6310(a). Commenters also asked whether a system that sends data to an infusion pump to... signal to an infusion pump to control the flow rate would not be an MDDS because, as the revised final...

Glucose Infusion into Exercising Dogs after Confinement: Rectal and Active Muscle Temperatures

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Kruk, B.; Nazar, K.; Falecka-Wieczorek, I.; Kaciuba-Uscilko, H.

1995-01-01

Intravenous glucose infusion into ambulatory dogs results in attenuation of exercise-induced increase of both rectal and thigh muscle temperatures. That glucose (Glu) infusion attenuates excessive increase in body temperature from restricted activity during confinement deconditioning. Intravenous glucose infusion attenuates the rise in exercise core temperature in deconditioned dogs by a yet undefined mechanism.

International survey on neuroradiological interventional and therapeutic devices and materials.

PubMed

van den Berg, René; Mayer, Thomas E

2015-12-01

A web-based survey was performed among the members of the World Federation of Interventional and Therapeutic Neuroradiology to determine the differences in availability, pricing, and performance of endovascular devices with special focus on coils, intra-arterial stroke devices, detachable balloons, and liquid embolic materials. The results of this survey show that the quality of the majority of interventional neuroradiology devices is good and compatibility issues are limited. Individual action towards suppliers is recommended to discuss the availability and pricing of devices and embolization materials. © The Author(s) 2015.

Paraplegia after contrast media application: a transient or devastating rare complication? Case report.

PubMed

Mielke, Dorothee; Kallenberg, Kai; Hartmann, Marius; Rohde, Veit

2016-05-01

The authors report the case of a 76-year-old man with a spinal dural arteriovenous fistula. The patient suffered from sudden repeated reversible paraplegia after spinal digital subtraction angiography as well as CT angiography. Neurotoxicity of contrast media (CM) is the most probable cause for this repeated short-lasting paraplegia. Intolerance to toxicity of CM to the vulnerable spinal cord is rare, and probably depends on the individual patient. This phenomenon is transient and can occur after both intraarterial and intravenous CM application.

Radiofrequency ablation during continuous saline infusion can extend ablation margins

PubMed Central

Ishikawa, Toru; Kubota, Tomoyuki; Horigome, Ryoko; Kimura, Naruhiro; Honda, Hiroki; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Yoshida, Toshiaki

2013-01-01

AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area. METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment. RESULTS: No liquid infusion was 17.3 ± 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 ± 3.3 mL) than with 5% glucose (21.4 ± 2.2 mL), 50% glucose (16.5 ± 0.9 mL) or no liquid infusion (17.3 ± 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose. CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence. PMID:23483097

Rapid Delivery of Cocaine Facilitates Acquisition of Self-Administration in Rats: An Effect Masked by Paired Stimuli

PubMed Central

Schindler, Charles W.; Cogan, Elizabeth S.; Thorndike, Eric B.; Panlilio, Leigh V.

2011-01-01

In general, faster infusions of cocaine are more likely to support behavior related to abuse than are slower infusions. However, some studies of cocaine self-administration in rats have failed to support this finding, possibly because the effect was masked by other factors. One such factor may be the pairing of a stimulus with the infusion, a procedure that is known to facilitate acquisition of drug self-administration. We compared fast and slow infusions by allowing groups of rats to acquire cocaine self-administration at a dose of 1 mg/kg/infusion, delivered over different durations (1.8 or 100 sec). Two groups were trained with either short or long infusions paired with a visual stimulus change (lights off), and two other groups were trained with short or long durations but with no stimulus change. Both groups trained with a paired stimulus acquired cocaine self-administration. With no stimulus change, the rats trained with the 1.8-sec infusion acquired cocaine self-administration at a rate comparable to the two groups that were trained with a paired stimulus. However, most rats in the group trained with the 100-sec infusion that was not accompanied by a stimulus change failed to acquire cocaine self-administration. The stimulus itself did not support responding. These results indicate that infusing a given dose of cocaine over a longer duration reduces its ability to support self-administration, but drug-paired stimuli can partially mask this effect by enhancing the effectiveness of slow infusions. PMID:21600912

Rapid delivery of cocaine facilitates acquisition of self-administration in rats: an effect masked by paired stimuli.

PubMed

Schindler, Charles W; Cogan, Elizabeth S; Thorndike, Eric B; Panlilio, Leigh V

2011-09-01

In general, faster infusions of cocaine are more likely to support behavior related to abuse than are slower infusions. However, some studies of cocaine self-administration in rats have failed to support this finding, possibly because the effect was masked by other factors. One such factor may be the pairing of a stimulus with the infusion, a procedure that is known to facilitate acquisition of drug self-administration. We compared fast and slow infusions by allowing groups of rats to acquire cocaine self-administration at a dose of 1mg/kg/infusion, delivered over different durations (1.8 or 100 s). Two groups were trained with either short or long infusions paired with a visual stimulus change (lights off), and two other groups were trained with short or long durations but with no stimulus change. Both groups trained with a paired stimulus acquired cocaine self-administration. With no stimulus change, the rats trained with the 1.8-s infusion acquired cocaine self-administration at a rate comparable to the two groups that were trained with a paired stimulus. However, most rats in the group trained with the 100-s infusion that was not accompanied by a stimulus change failed to acquire cocaine self-administration. The stimulus itself did not support responding. These results indicate that infusing a given dose of cocaine over a longer duration reduces its ability to support self-administration, but drug-paired stimuli can partially mask this effect by enhancing the effectiveness of slow infusions. Published by Elsevier Inc.

Closed-loop Continuous Infusions of Etomidate and Etomidate Analogs in Rats

PubMed Central

Cotten, Joseph F.; Le Ge, Ri; Banacos, Natalie; Pejo, Ervin; Husain, S. Shaukat; Williams, James H.; Raines, Douglas E.

2012-01-01

Background Etomidate is a sedative–hypnotic that is often given as a single intravenous bolus but rarely as an infusion because it suppresses adrenocortical function. Methoxycarbonyl etomidate and (R)-ethyl 1-(1-phenylethyl)-1H-pyrrole-2-carboxylate (carboetomidate) are etomidate analogs that do not produce significant adrenocortical suppression when given as a single bolus. However, the effects of continuous infusions on adrenocortical function are unknown. In this study, we compared the effects of continuous infusions of etomidate, methoxycarbonyl etomidate, and carboetomidate on adrenocortical function in a rat model. Methods A closed-loop system using the electroencephalographic burst suppression ratio as the feedback was used to administer continuous infusions of etomidate, methoxycarbonyl etomidate, or carboetomidate to Sprague–Dawley rats. Adrenocortical function was assessed during and after infusion by repetitively administering adrenocorticotropic hormone 1–24 and measuring serum corticosterone concentrations every 30 min. Results The sedative–hypnotic doses required to maintain a 40% burst suppression ratio in the presence of isoflurane, 1%, and the rate of burst suppression ratio recovery on infusion terminationvaried(methoxycarbonyletomidate>carboetomidate > etomidate). Serum corticosterone concentrations were reduced by 85% and 56% during 30-min infusions of etomidate and methoxycarbonyl etomidate, respectively. On infusion termination, serum corticosterone concentrations recovered within 30 min with methoxycarbonyl etomidate but persisted beyond an hour with etomidate. Carboetomidate had no effect on serum corticosterone concentrations during or after continuous infusion. Conclusions Our results suggest that methoxycarbonyl etomidate and carboetomidate may have clinical utility as sedative–hypnotic maintenance agents when hemodynamic stability is desirable. PMID:21572317

High-Dose Continuous Infusion Beta-lactam Antibiotics for the Treatment of Resistant Pseudomonas aeruginosa Infections in Immunocompromised Patients

PubMed Central

Moriyama, Brad; Henning, Stacey A.; Childs, Richard; Holland, Steven M.; Anderson, Victoria L.; Morris, John C.; Wilson, Wyndham H.; Drusano, George L.; Walsh, Thomas J.

2011-01-01

OBJECTIVE To report a case series of high-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections. CASE SUMMARY Continuous infusion ceftazidime or aztreonam was administered to achieve target drug levels at or above the MIC when possible in three patients with P. aeruginosa infections. The maximal calculated target drug level was 100 mg/L. In the first patient with primary immunodeficiency, neutropenia, and aggressive cutaneous T cell lymphoma/leukemia, continuous infusion ceftazidime (6.5 to 9.6 g/day) was used to successfully treat multidrug-resistant P. aeruginosa bacteremia. In the second patient with leukocyte adhesion deficiency type 1, continuous infusion aztreonam (8.4 g/day) was used to successfully treat multidrug-resistant P. aeruginosa wound infections. In the third patient with severe aplastic anemia, continuous infusion ceftazidime (7 to 16.8 g/day) was used to treat P. aeruginosa pneumonia and bacteremia. In each patient, the bacteremia cleared, infected wounds healed, and pneumonia improved in response to continuous infusion ceftazidime or aztreonam. DISCUSSION Treatment strategies for multidrug-resistant P. aeruginosa infections are limited. A novel treatment strategy when no other options are available is the administration of existing beta-lactam antibiotics by continuous infusion in order to maximize their pharmacodynamic activity. High-dose continuous infusion ceftazidime or aztreonam was used for the successful treatment of resistant systemic P. aeruginosa infections in three chronically immunocompromised patients. CONCLUSION Continuous infusion beta-lactam antibiotics are a potentially useful treatment strategy for resistant P. aeruginosa infections in immunocompromised patients. PMID:20371747

Increased Nutrient Sensitivity and Plasma Concentrations of Enteral Hormones during Duodenal Nutrient Infusion in Functional Dyspepsia

PubMed Central

Bharucha, Adil E.; Camilleri, Michael; Burton, Duane D.; Thieke, Shannon L.; Feuerhak, Kelly J.; Basu, Ananda; Zinsmeister, Alan R.

2015-01-01

Objectives Functional dyspepsia is predominantly attributed to gastric sensorimotor dysfunctions. The contribution of intestinal chemosensitivity to symptoms is not understood. We evaluated symptoms and plasma hormones during enteral nutrient infusion and the association with impaired glucose tolerance and quality-of-life (QOL) scores in functional dyspepsia vs health. Design Enteral hormonal responses and symptoms were measured during isocaloric and isovolumic dextrose and lipid infusions into the duodenum in 30 patients with functional dyspepsia (n=27) or nausea and vomiting (n=3) and 35 healthy controls. Infusions were administered in randomized order over 120 minutes each, with a 120-minute washout. Cholecystokinin, glucose-dependent insulinotropic peptide, glucagonlike peptide 1 (GLP1), and peptide YY were measured during infusions. Results Moderate or more severe symptoms during lipid (4 controls vs 14 patients) and dextrose (1 control vs 12 patients) infusions were more prevalent in patients than controls (P≤.01), associated with higher dyspepsia symptom score (P=.01), worse QOL (P=.01), and greater plasma hormone concentrations (eg, GLP1 during lipid infusion). Moderate or more severe symptoms during enteral infusion explained 18%, and depression score explained 21%, of interpatient variation in QOL. Eight patients had impaired glucose tolerance, associated with greater plasma GLP1 and peptide YY concentrations during dextrose and lipid infusions, respectively. Conclusions Increased sensitivity to enteral dextrose and lipid infusions was associated with greater plasma enteral hormone concentrations, more severe daily symptoms, and worse QOL in functional dyspepsia. These observations are consistent with the hypothesis that enteral hormones mediate increased intestinal sensitivity to nutrients in functional dyspepsia. PMID:25403365

Toxicological study of a new maintenance fluid, Veen 3G, in rats.

PubMed

Kamei, J; Onodera, K; Kawaguchi, M; Shibata, M; Kagawa, M; Wachi, M; Kojima, J

2002-10-01

A study of the different volume and infusion rates of a new maintenance fluid, Veen 3G, on the general conditions of rats was investigated during the 14 days after infusion. In Experiment I, 100 ml/kg and 200 ml/kg of Veen 3G were infused at a rate of 300 ml/kg/h in male and female rats. Results were compared with those for Gurunon Ringer solution (GRS) in male and female rats. We observed only transient polyuria in animals administered by each dose of Veen 3G and GRS for 0-15 min after infusion. Necropsy was not observed in any of the animals tested 14 days after infusion. In Experiment II, 200 ml/kg of Veen 3G was infused at rates of 200, 400, 800 and 1600 ml/kg/h in male rats. At 800 and 1600 ml/kg/h, irregular respiration and decrease in movement were observed concomitantly with polyuria. Three out of 4 rats died immediately after the infusion of Veen 3G at a rate of 1600 ml/kg/h, and one rat was still alive 14 days after the infusion. In this experiment, 200 ml/kg Veen 3G was safe when we infused at a rate of less than 400 ml/kg/h in male rats. Since this rate is about 27-80 times higher than that used clinically in maintenance treatment, Veen 3G is suggested to be safe, with the exception of polyuria, in clinical situations at the standard infusion rate (5-15 ml/kg/h).

Hepatic glucose output in humans measured with labeled glucose to reduce negative errors

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

Levy, J.C.; Brown, G.; Matthews, D.R.

Steele and others have suggested that minimizing changes in glucose specific activity when estimating hepatic glucose output (HGO) during glucose infusions could reduce non-steady-state errors. This approach was assessed in nondiabetic and type II diabetic subjects during constant low dose (27 mumol.kg ideal body wt (IBW)-1.min-1) glucose infusion followed by a 12 mmol/l hyperglycemic clamp. Eight subjects had paired tests with and without labeled infusions. Labeled infusion was used to compare HGO in 11 nondiabetic and 15 diabetic subjects. Whereas unlabeled infusions produced negative values for endogenous glucose output, labeled infusions largely eliminated this error and reduced the dependence ofmore » the Steele model on the pool fraction in the paired tests. By use of labeled infusions, 11 nondiabetic subjects suppressed HGO from 10.2 +/- 0.6 (SE) fasting to 0.8 +/- 0.9 mumol.kg IBW-1.min-1 after 90 min of glucose infusion and to -1.9 +/- 0.5 mumol.kg IBW-1.min-1 after 90 min of a 12 mmol/l glucose clamp, but 15 diabetic subjects suppressed only partially from 13.0 +/- 0.9 fasting to 5.7 +/- 1.2 at the end of the glucose infusion and 5.6 +/- 1.0 mumol.kg IBW-1.min-1 in the clamp (P = 0.02, 0.002, and less than 0.001, respectively).« less

Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role.

PubMed

Roberts, Jason A; Paratz, Jennifer; Paratz, Elizabeth; Krueger, Wolfgang A; Lipman, Jeffrey

2007-07-01

Continuous infusion of beta-lactam antibiotics has been widely promoted to optimise their time-dependent activity. Increasing evidence is emerging suggesting potential benefits in patient populations with altered pathophysiology, such as seriously ill patients. From a pharmacokinetic viewpoint, much information supports higher trough concentrations of beta-lactam antibiotics when administered by continuous infusion. This advantage of continuous infusion translates into a superior ability to achieve pharmacodynamic targets, particularly when the minimum inhibitory concentration (MIC) of the pathogen is >or=4 mg/L. One drawback of continuous infusion may be limited physicochemical stability. This issue exists particularly for carbapenem antibiotics whereby prolonged infusions (i.e. >3h) can be used to improve the time above the MIC compared with conventional bolus dosing. Few studies have examined clinical outcomes of bolus and continuous dosing of beta-lactam antibiotics in seriously ill patients. No statistically significant differences have been shown for: mortality; time to normalisation of leukocytosis or pyrexia; or duration of mechanical ventilation, intensive care unit stay or hospital stay. Some evidence suggests improved clinical cure and resolution of illness with continuous infusion in seriously ill patients. Pharmacoeconomic advantages of continuous infusion of beta-lactam antibiotics are well characterised. Available data suggest that seriously ill patients with severe infections requiring significant antibiotic courses (>or=4 days) may be the subgroup that will achieve better outcomes with continuous infusion.

Randomized trial of intermittent or continuous amnioinfusion for variable decelerations.

PubMed

Rinehart, B K; Terrone, D A; Barrow, J H; Isler, C M; Barrilleaux, P S; Roberts, W E

2000-10-01

To determine whether continuous or intermittent bolus amnioinfusion is more effective in relieving variable decelerations. Patients with repetitive variable decelerations were randomized to an intermittent bolus or continuous amnioinfusion. The intermittent bolus infusion group received boluses of 500 mL of normal saline, each over 30 minutes, with boluses repeated if variable decelerations recurred. The continuous infusion group received a bolus infusion of 500 mL of normal saline over 30 minutes and then 3 mL per minute until delivery occurred. The ability of the amnioinfusion to abolish variable decelerations was analyzed, as were maternal demographic and pregnancy outcome variables. Power analysis indicated that 64 patients would be required. Thirty-five patients were randomized to intermittent infusion and 30 to continuous infusion. There were no differences between groups in terms of maternal demographics, gestational age, delivery mode, neonatal outcome, median time to resolution of variable decelerations, or the number of times variable decelerations recurred. The median volume infused in the intermittent infusion group (500 mL) was significantly less than that in the continuous infusion group (905 mL, P =.003). Intermittent bolus amnioinfusion is as effective as continuous infusion in relieving variable decelerations in labor. Further investigation is necessary to determine whether either of these techniques is associated with increased occurrence of rare complications such as cord prolapse or uterine rupture.

[Usefulness of Bolus Administration Using the FLEX Mode(Bolus Infusion Mode)for Baclofen Tolerance].

PubMed

Tanaka, Kazunori

2017-02-01

Intrathecal baclofen(ITB)is used to treat intractable spasticity of various etiologies and can provide better control of spasticity through the adjustment of the dose administered through the pump. However, in patients who develop tolerance to baclofen with the standard simple continuous mode, a sharp increase in dose becomes necessary, and spasticity can become harder to control. We investigated whether switching from the simple continuous mode to the bolus infusion mode was effective in controlling spasticity in patients with baclofen tolerance. We reported four patients undergoing ITB therapy at our facility who were considered to have developed baclofen tolerance. We observed the number of bolus infusions and total dose suitable for maintaining spasticity control after switching from the simple continuous mode to the bolus infusion mode. After switching to the bolus infusion mode, the total dose could be reduced in the short term; however, in the long term, the frequency of bolus infusions had to be increased to maintain spasticity control. Two years after changing to bolus infusion six times a day, the total dose was higher than that in the simple continuous mode for two of the four patients, and was the same level in the other two patients. Our four cases suggest that bolus infusion is effective in patients with baclofen tolerance during ITB therapy. Therefore, the conditions of bolus infusion should be further investigated.

Intravenous infusion of hexamethonium and atropine but not propranolol diminishes apolipoprotein A-IV gene expression in rat ileum.

PubMed

Sonoyama, K; Tajima, K; Fujiwara, R; Kasai, T

2000-03-01

To clarify the role of neural factors in the regulation of apolipoprotein (apo) A-IV expression in the small intestine, we investigated the effect of neural blockers on mRNA levels of apo A-IV in rat small intestine. Either ganglionic blocker (hexamethonium), cholinergic blocker (atropine) or beta-adrenergic blocker (propranolol) was infused intravenously to unrestrained conscious rats for 8 h, and then total RNA was isolated from the small intestine and analyzed using Northern hybridization. Apo A-IV mRNA levels in the ileum were significantly lower in hexamethonium- or atropine-infused rats than in saline- (control) or propranolol-infused rats. Immunoblot analysis showed no difference in plasma apo A-IV concentrations between hexamethonium- and saline-infused groups. The lower mRNA levels of apo A-IV in the ileum of hexamethonium-infused rats were observed even in bile-drained rats, indicating that the lower expression was not due to any changes in bile availability. The ileal apo A-IV mRNA levels were significantly higher in rats infused with lipid emulsion into the ileum than in rats infused with glucose-saline, and the concomitant infusion of intravenous hexamethonium did not affect the higher levels of apo A-IV mRNA. These results suggest that the basal expression of the ileal A-IV gene is at least partially regulated in a site-specific manner by cholinergic neurons.

The Effect of Tubing Dwell Time on Insulin Adsorption During Intravenous Insulin Infusions

PubMed Central

Vital-Carona, Jessica; Faustino, E. Vincent S.

2012-01-01

Abstract Background Insulin adsorbs to plastic tubing, which decreases the concentration of an insulin solution delivered from an intravenous infusion set. Dwelling insulin within tubing before starting the infusion decreases adsorption but delays treatment initiation and wastes time in infusion preparation. The lack of data on dwell time effects results in wide variability in practice. We aim to determine the effect of dwell time on insulin concentration from intravenous infusion tubing. Materials and Methods In this in vitro study, we used insulin solutions with concentrations of 0.1 unit/mL, 1 unit/mL, and 10 units/mL. Each solution dwelled in intravenous infusion sets for 0, 15, 30, or 60 min. After the dwell, we measured insulin concentrations from the solution bags and tubing. We repeated each insulin concentration–dwell time combination five times. Comparisons were performed using analyses of variance. Results For each of the three insulin concentrations, the mean insulin concentrations from the tubing were not significantly different between dwell times. Duration of dwell time did not affect insulin adsorption in polypropylene intravenous infusion sets. Conclusions We recommend that following a 20-mL flush, insulin infusions can be started without any dwell time. Removal of dwell times may improve clinical practice by minimizing preparation time and will allow faster initiation of insulin infusion therapy. PMID:22746979

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.

Influence of dexmedetomidine on cognitive function in volunteers.

PubMed

Yatabe, Tomoaki; Tamura, Takahiko; Yamashita, Koichi; Yokoyama, Masataka

2016-09-01

Some outpatient procedures are performed under sedation with dexmedetomidine, although the effect of dexmedetomidine on cognitive function remains unclear. This study investigated the effect of dexmedetomidine on cognitive function in healthy volunteers. Observation study in volunteers. University-affiliated teaching hospital. Six healthy volunteers. After infusion of a 6-μg/kg per hour loading dose of dexmedetomidine for 10 minutes, a maintenance infusion of 0.4 μg/kg per hour was administered for 4 hours. Cognitive function was evaluated before infusion (baseline) and at 2, 4, 6, and 8 hours after infusion. Cognitive function, response speed, accuracy, and consistency were measured by CogHealth. Depth of sedation was evaluated at 1-hour intervals by evaluating the Bispectral Index. Data are presented as the change from baseline. The Bispectral Index value was significantly lower from 10 minutes to 6 hours after infusion versus the pre-infusion value. Response speed was also significantly lower at 2 hours and 4 hours after infusion (92 ± 8%, P< .0001; 93 ± 6%, P< .0001), as was consistency (96 ± 7%, P= .0009; 96 ± 5%, P= .0003). Response accuracy was unaltered by the infusion. Dexmedetomidine slightly reduced response speed and consistency, but did not affect response accuracy. Cognitive function was restored to pre-administration values 2 hours after the infusion of dexmedetomidine was discontinued. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of branchial V-H(+)-ATPase, Na(+)/K(+)-ATPase and NHE2 in response to acid and base infusions in the Pacific spiny dogfish (Squalus acanthias).

PubMed

Tresguerres, Martin; Katoh, Fumi; Fenton, Heather; Jasinska, Edyta; Goss, Greg G

2005-01-01

To study the mechanisms of branchial acid-base regulation, Pacific spiny dogfish were infused intravenously for 24 h with either HCl (495+/- 79 micromol kg(-1) h(-1)) or NaHCO(3) (981+/-235 micromol kg(-1) h(-1)). Infusion of HCl produced a transient reduction in blood pH. Despite continued infusion of acid, pH returned to normal by 12 h. Infusion of NaHCO(3) resulted in a new steady-state acid-base status at approximately 0.3 pH units higher than the controls. Immunostained serial sections of gill revealed the presence of separate vacuolar proton ATPase (V-H(+)-ATPase)-rich or sodium-potassium ATPase (Na(+)/K(+)-ATPase)-rich cells in all fish examined. A minority of the cells also labeled positive for both transporters. Gill cell membranes prepared from NaHCO(3)-infused fish showed significant increases in both V-H(+)-ATPase abundance (300+/-81%) and activity. In addition, we found that V-H(+)-ATPase subcellular localization was mainly cytoplasmic in control and HCl-infused fish, while NaHCO(3)-infused fish demonstrated a distinctly basolateral staining pattern. Western analysis in gill membranes from HCl-infused fish also revealed increased abundance of Na(+)/H(+) exchanger 2 (213+/-5%) and Na(+)/K(+)-ATPase (315+/-88%) compared to the control.

Vegetative and reproductive growth of salt-stressed chickpea are carbon-limited: sucrose infusion at the reproductive stage improves salt tolerance

PubMed Central

Khan, Hammad A.; Siddique, Kadambot H.M.

2017-01-01

Abstract Reproductive processes of chickpea (Cicer arietinum L.) are particularly sensitive to salinity. We tested whether limited photoassimilate availability contributes to reproductive failure in salt-stressed chickpea. Rupali, a salt-sensitive genotype, was grown in aerated nutrient solution, either with non-saline (control) or 30mM NaCl treatment. At flowering, stems were either infused with sucrose solution (0.44M), water only or maintained without any infusion, for 75 d. The sucrose and water infusion treatments of non-saline plants had no effect on growth or yield, but photosynthesis declined in response to sucrose infusion. Salt stress reduced photosynthesis, decreased tissue sugars by 22–47%, and vegetative and reproductive growth were severely impaired. Sucrose infusion of salt-treated plants increased total sugars in stems, leaves and developing pods, to levels similar to those of non-saline plants. In salt-stressed plants, sucrose infusion increased dry mass (2.6-fold), pod numbers (3.8-fold), seed numbers (6.5-fold) and seed yield (10.4-fold), yet vegetative growth and reproductive failure were not rescued completely by sucrose infusion. Sucrose infusion partly rescued reproductive failure in chickpea by increasing vegetative growth enabling more flower production and by providing sucrose for pod and seed growth. We conclude that insufficient assimilate availability limits yield in salt-stressed chickpea. PMID:27140441