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Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research

ADVANCED DRUG DELIVERY REVIEWS 2001年第2-3期47卷 209-228页

作者： Krafft, MP Inst Charles Sadron F-67083 Strasbourg France

The specific properties of fluorocarbons, exceptional chemical and biological inertness, high gas-dissolving capacity, low surface tension, excellent spreading characteristics and high fluidity, have triggered numerous applications of these compounds in oxygen delivery. An injectable emulsion of fluorocarbon-in-water destined to deliver oxygen to tissues at risk of hypoxia has now completed Phase III clinical trials in Europe. A neat fluorocarbon is currently investigated in Phase II for treatment of acute respiratory failure by liquid ventilation. Fluorinated lipids and fluorinated surfactants can be used to elaborate and stabilize various colloidal systems, including different types of emulsions, vesicles and tubules, that also show promise for controlled release drug delivery. (C) 2001 Elsevier Science B.V. All rights reserved.

关键词：缺氧/药物疗法药物释放系统/方法药物稳定性乳状剂/投药和剂量乳状剂/化学氟碳化合物/投药和剂量氟碳化合物/化学凝胶类/投药和剂量凝胶类/化学液体通气微胶粒表面活性剂/投药和剂量表面活性剂/化学人类

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Contrast echocardiography clarifies uninterpretable wall motion in intensive care unit patients

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期35卷 485-490页

作者： Reilly, JP Tunick, PA Timmermans, RJ Stein, B Rosenzweig, BP Kronzon, I NYU Sch Med Dept Med Noninvas Cardiol Lab New York NY 10016 USA

OBJECTIVES The study examined the value of contrast echocardiography in the ventricular (LV) wall motion in intensive care unit (ICU) patients. BACKGROUND Echocardiograms done in the ICU are often suboptimal. The most common indication is the evaluation of LV wall motion and ejection fraction (EF). METHODS Transthoracic echocardiograms were done in 70 unselected ICU patients. Wall motion was evaluated on standard echocardiography (SE),: harmonic echocardiography (HE), and after intravenous (IV) contrast echocardiography (CE) using a score for each of 16 segments. A confidence score was also given for each segment with:each technique (unable to judge;not sure;sure). The EF was estimated visually for each technique, and a confidence score was applied to the EF. RESULTS Uninterpretable wall motion was present in 5.4 segments/patient on SE, 4.4 on HE (p = 0.2), and 1.1 on CE (p < 0.0001). An average of 7.8 segments were read with surety on SE, 9.2 on HE (p = 0.1), and 13.7 on CE (p < 0.0001). Ejection fraction was uninterpretable in 23% on SE, 13% on HE (p = 0.14), and 0%, On CE (p = 0.002 vs. HE;p < 0.0001 vs. SE). The EF was read with surety in 56% of patients on SE, 62% on HE (p = 0.47), and 91% on CE (p < 0.0001). Thus, wall motion was:seen with more confidence on CE. More importantly, the actual readings of segmental wall motion and EF significantly differed using CE. CONCLUSIONS CE should be used in all ICU patients with suboptimal transthoracic echocardiograms. (J Am Coll Cardiol 2000;35:485-90) (C) 2000 by the American College of Cardiology.

关键词：白蛋白类/投药和剂量造影剂危重病超声心动描记术/方法氟碳化合物/投药和剂量心室/诊断显像心室/病理生理学注射静脉内重症监护病房微球体心肌收缩观察者偏差结果可重复性回顾性研究每搏输出量心室功能障碍左/诊断显像心室功能障碍左/病理生理学成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation

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ANNALS OF THORACIC SURGERY 1999年第2期67卷 332-339页

作者： Itano, H Aoe, M Ichiba, S Yamashita, M Date, H Andou, A Shimizu, N Okayama Univ Sch Med Dept Surg 2 Okayama 7008558 Japan

Background. This study was designed to investigate the efficacy of partial liquid ventilation (PLV) on acute allograft dysfunction after lung transplantation. Methods. The canine left lung allotransplantation model was used, with the graft preserved in 4 degrees C lowpotassium dextran glucose solution for 18 hours. The control group (n = 6) had conventional mechanical ventilation, and the PLV group (n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated. After the evaluation, myeloperoxidase activity of the graft tissue was assayed. Results. All dogs survived for 360 minutes. In the PT,V group, Pao, shunt fraction, and alveolar to arterial gradient for O-2, were si,significantly better than those in the control group after 120, 180, and 120 minutes, respectively (p < 0.05). After 240 minutes, peak airway pressure became significantly lower than that in the control group (p < 0.05). The Pao, at 360 minutes was 102 +/- 55 mm Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/- 5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group was lower than that in the control group. Conclusions. The study shows that PLV alleviated acute allograft dysfunction after lung transplantation. (C) 1999 by The Society of Thoracic Surgeons.

关键词：氟碳化合物/投药和剂量肺/血液供给肺/病理学肺移植/病理学肺移植/生理学氧/血液肺换气/生理学再灌注损伤/病理学再灌注损伤/病理生理学再灌注损伤/治疗呼吸人工移植同种动物狗

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B-mode enhancement of the liver with microbubble contrast agent: A blinded study in rabbits with VX2 tumors

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ACADEMIC RADIOLOGY 2001年第8期8卷 734-740页

作者： Girard, MS Kono, Y Sirlin, CB Baker, KG Deiranieh, LH Mattrey, RF Univ Calif San Diego Dept Radiol La Jolla CA 92093 USA

Rationale and Objectives. The purpose of this study was to evaluate the accuracy of contrast material-enhanced sonography in the detection of liver lesions by using an animal model, Materials and Methods. A total of 36 rabbits, 12 normal and 24 with one, two, or more VX2 tumors implanted percutaneously, were imaged on an Acuson 128XP/10 with a 7-MHz sector transducer by a sonographer blinded to the study assignments. The sonographer assigned rabbits to four groups (no, one, two, more than two tumors) based on the number of lesions detected before and then after the intravenous bolus injection of 0.5 mL of AF0150. S-VHS video segments or pre- and postcontrast images were separated, randomized, and evaluated by a blinded reader. Necropsy served as the gold standard. Results. Classification of rabbits as normal or tumor bearing on the precontrast images produced three false-positive results and three false-negative results for the blinded sonographer and six false-positive results and two false-negative results for the blinded reader. On postcontrast images, all rabbits were correctly classified by both observers. The correlation of the classification of whether rabbits had no, one, two, or more tumors relative to the pathologic classification precontrast images was poor to fair (kappa = 0.349 +/- 0.099 for the sonographer and 0.274 +/- 0.111for the reader), whereas the postcontrast correlation was good to excellent (kappa = 0.924 +/- 0.099 for the sonographer and 0.809 +/- 0.076 for the reader). Conclusion. AF0150 markedly increased the ability of the sonographer and the blinded reader to distinguish normal from tumor-bearing animals and improved the classification of rabbits with more than one liver tumor.

关键词：造影剂/投药和剂量造影剂/药代动力学氟碳化合物/投药和剂量氟碳化合物/诊断应用氟碳化合物/药代动力学肝/超声检查肝肿瘤实验性/超声检查模型动物肿瘤移植前瞻性研究敏感性与特异性单盲法超声检查/方法动物兔

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Pars plana vitrectomy without scleral buckle for pseudophakic retinal detachments

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OPHTHALMOLOGY 1999年第9期106卷 1811-1815页

作者： Campo, RV Sipperley, JO Sneed, SR Park, DW Dugel, PU Jacobsen, J Flindall, RJ Retinal Consultants Arizona Phoenix AZ 85006 USA

Objective: To report the anatomic and visual results of primary pars plana vitrectomy (PPV) without scleral buckling to repair primary rhegmatogenous retinal detachments in pseudophakic eyes. Design: Nonrandomized, prospective, comparative clinical trial. Participants: Two hundred eighty-three consecutive patients (294 eyes) with pseudophakia, peripheral retinal tears, and new rhegmatogenous retinal detachments were treated according to the surgery protocol. Intervention: Patients underwent PPV with fluid-gas exchange and endolaser to repair the retinal detachment. Two hundred sixty-four patients (275 eyes) were followed from 6 months to 6 years and 8 months with an average follow-up of 19 months. Main Outcome Measures: Reattachment of the retina and visual outcome were compared to previously published studies. Results: Of 97 eyes with a macula-attached rhegmatogenous retinal detachment, 88 eyes (91%) were reattached with a single operation, and of the 178 eyes with a macula-detached retinal detachment, 153 (86%) eyes were reattached with a single operation. In 241 (88%) of 275 eyes, the retina was reattached with a single operation, and in 265 (96%) of 275 eyes, the retina was ultimately reattached with subsequent operations. The median initial visual acuity was 20/300, and the median final visual acuity was 20/40. The rate of reattachment with one operation was similar for eyes with an anterior chamber intraocular lens (91%) and for eyes with a posterior chamber intraocular lens (88%). Refractive error measurements obtained in 81 eyes were essentially unchanged. The mean change in refractive error was -0.15 diopter. Seventeen eyes (6%) developed macular puckers requiring surgery, 46 eyes (17%) developed cystoid macular edema, and 6 eyes (2%) developed full-thickness macular holes. Conclusion: Primary PPV with fluid-gas exchange and laser is a safe, effective method to repair primary pseudophakic retinal detachments. The anatomic reattachment rate and the visual ac

关键词：氟碳化合物/投药和剂量随访研究晶体人工手术后并发症前瞻性研究假晶状体/并发症视网膜脱离/病因学视网膜脱离/外科学视网膜穿孔/病因学视网膜穿孔/外科学巩膜扣带术硫六氟化物/投药和剂量治疗结果视敏度玻璃体切除术人类

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Enhanced mortality from perfluorocarbon administration in a rat model of kerosene aspiration

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JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY 1999年第7期37卷 855-859页

作者： Burns, MJ Dickson, EW Sivilotti, MLA Hocker, M Porcaro, WA Beth Israel Deaconess Med Ctr Div Emergency Med Boston MA 02215 USA Univ Massachusetts Med Ctr Worcester MA USA Brigham & Womens Hosp Boston MA 02115 USA

Background: Aspiration of low-viscosity hydrocarbons may lead to fulminant pneumonitis and acute respiratory distress syndrome. Animal and human studies suggest that partial liquid ventilation with perfluorocarbon improves gas exchange and pulmonary function in acute respiratory failure. The objective of this investigation was to determine the effect of intratracheal perfluorocarbon administration and a brief period of partial liquid ventilation on survival in a rat model of severe hydrocarbon aspiration. Methods: Two randomized, nonblinded, controlled experiments were performed. First, male Wistar rats (n = 12) were given 0.3 mL/kg kerosene via direct intratracheal instillation and after 5 minutes were randomized to partial liquid ventilation or standard gas ventilation (control) groups. Partial liquid ventilation rats (n = 6) received 20 mL/kg of pre-oxygenated FC-77 intratracheally and positive-pressure gas ventilation (FiO(2) = 1.0), and control rats (n = 6) received positive-pressure gas ventilation alone. Animals were observed for survival and 7-day mortality was compared using the Fisher Exact test. The study was then repeated in 12 additional animals using a 15-minute interval between kerosene instillation and treatment (PLV vs control). Results: Mortality was significantly greater in the partial liquid ventilation group (5 of 6;83%) as compared to the control group (1 of 6;17% [p = 0.039]). Results were identical in the repeat study. All animals that died succumbed from acute respiratory failure within 24 hours of kerosene instillation. Conclusion: In this rat model of severe kerosene aspiration, intratracheal perfluorocarbon administration and a brief period of partial liquid ventilation proved detrimental and significantly increased mortality.

关键词：投药吸入氟碳化合物/投药和剂量氟碳化合物/毒性插管法气管内煤油/毒性大鼠 Wistar 可重复性结果呼吸人工动物男(雄)性大鼠

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Comparison of visual function after foveal translocation with 360° retinotomy and with scleral shortening in a patient with bilateral myopic neovascular maculopathy

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AMERICAN JOURNAL OF OPHTHALMOLOGY 2000年第4期130卷 525-527页

作者： Fujikado, T Ohji, M Hosohata, J Hayashi, A Oda, K Tano, Y Osaka Univ Sch Med Dept Appl Med Engn Suita Osaka 5650871 Japan Osaka Univ Sch Med Dept Ophthalmol Suita Osaka 5650871 Japan Tokyo Womens Christian Univ Dept Commun Tokyo Japan

PURPOSE: To compare the visual outcome after foveal translocation by scleral shortening and that after 360 degrees retinotomy with extraocular muscle surgery in a patient with bilateral myopic neovascular maculopathy. METHODS: Case report. RESULTS: A 52-year-old woman with bilateral myopic neovascular maculopathy underwent foveal translocation with scleral shortening in the left eye, and visual acuity improved from 20/70 to 20/30. However, choroidal neovascularization recurred, and the final visual acuity was 20/40 after excision of the choroidal neovascularization. Foveal translocation with 360 degrees retinotomy was performed on the right eye, and visual acuity improved from 20/150 to 20/30. The critical print size was better, and the retinal sensitive area was larger in the right eye. CONCLUSION: The better reading ability shown by foveal translocation by a 360 degrees retinotomy compared with scleral shortening may stem from a larger retinal sensitive area obtained by this method. (C) 2000 by Elsevier Science Inc. All rights reserved.

关键词：脉络膜新生血管化/病理生理学脉络膜新生血管化/外科学荧光素血管造影术氟碳化合物/投药和剂量中央凹/移植激光凝固术近视/病理生理学近视/外科学动眼肌/外科学复发巩膜/外科学硅油类/投药和剂量视敏度视野玻璃体切除术女(雌)性人类中年人

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Safety assessment of perflenapent emulsion for echocardiographic contrast enhancement in patients with congestive heart failure or chronic obstructive pulmonary disease

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AMERICAN HEART JOURNAL 2000年第6期139卷 1077-1080页

作者： Kitzman, DW Wesley, DJ Wake Forest Univ Sch Med Cardiol Sect Dept Med Winston Salem NC 27157 USA

Background Perflenapent injectable emulsion is a newer echocardiographic contrast agent that provides chamber opacification and improved endocardial border delineation. In >1000 patients tested, adverse effects have been minimal. However, previous studies have included few patients with congestive heart failure (CHF) or severe chronic obstructive pulmonary disease (COPD). Because of their reduced cardiopulmonary reserve, these patients might be at greater risk for adverse events. Methods and Results The safety of perflenapent emulsion was evaluated in ambulatory patients with New York Heart Association class III to IV congestive heart failure (CHF) or severe obstructive pulmonary disease (COPD). In 2 separate multicenter, phase II, randomized, double-blind, placebo-controlled, single-administration clinical trials, 146 patients in the CHF study and 134 patients in the COPD study received either perflenapent emulsion or saline placebo during an echocardiographic examination. Perflenapent emulsion was well tolerated in patients with CHF or COPD. The adverse event rates with perflenapent emulsion (15%) were similar to those with saline (11%;P = .43) in the combined groups, and similar findings were seen when analyzed by CHF or COPD groups separately. All adverse events were rated as mild, required no treatment, resolved spontaneously, and left no sequelae. Changes from baseline in vital signs, pulse oximetry, electrocardiography, and laboratory tests were similar between treatment groups. Conclusions These data support the safety of perflenapent emulsion for contrast echocardiography in stable ambulatory patients with CHF or COPD.

关键词：造影剂双盲法药物评价超声心动描记术/方法乳状剂氟碳化合物/投药和剂量氟碳化合物/诊断应用用力呼气量/药物作用注射静脉内肺疾病阻塞性/病理生理学肺疾病阻塞性/超声检查门诊病人安全老年人人类

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Efficacy and time-efficiency of a "sonographer-driven" contrast echocardiography protocol in a high-volume echocardiography laboratory

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AMERICAN HEART JOURNAL 2003年第3期145卷 535-541页

作者： Castello, R Bella, JN Rovner, A Swan, J Smith, J Shaw, L Univ Hosp Cleveland Dept Med Div Cardiol Cleveland OH 44106 USA Case Western Reserve Univ Sch Med Cleveland OH USA Emory Univ Atlanta GA 30322 USA

Background Contrast echocardiography (CE) has not gained widespread use despite numerous studies, demonstrating its efficacy in the assessment of left ventricular (LV) function. Methods We sought to determine whether CE could be used in a high-volume echocardiography laboratory in a clinically effective and time efficient manner. We implemented a protocol with a feasibility phase and an established phase. Cost-benefit analyses were done on the basis of time use. Results During the feasibility and established phases, data on 119 and 672 patients, respectively, were obtained. After a "sonographer-driven" protocol, contrast studies represented 7% to 8% of the total number of routine transthoracic and stress studies: Stress studies accounted for only 15% of the total number of contrast studies. Obesity was the most common indication for contrast use. LV visualization indices and wall thickening assessment, as evaluated by 2 blinded readers, were significantly improved with CE compared with second harmonic imaging alone. The time to make the decision to use CE and the time taken to administer contrast decreased significantly from the feasibility phase to the established phase (8.3 +/- 5 vs 7.6 +/- 5 min, P < .01, and 13.4 +/- 10 vs 10.2 +/- 5 min, P < .001, respectively). On the basis of,time use only, a cost analysis indicated that savings were obtained at a 10-minute reduction in study time. Conclusions A "sonographer-driven" CE protocol for LV assessment is feasible in high-volume echocardiography laboratories. It is clinically effective because it significantly improves LV global and regional wall motion visualization. A "sonographer-driven" CE protocol can reduce decision and administration times substantially, thus making CE time-efficient.

关键词：白蛋白类/投药和剂量白蛋白类/经济学卫生保健辅助人员/心理学医务工作者的态度临床方案造影剂/投药和剂量造影剂/经济学费用效益分析超声心动描记术/经济学超声心动描记术/方法超声心动描记术/统计学和数值数据超声心动描记术压力/方法可行性研究氟碳化合物/投药和剂量氟碳化合物/经济学实验室技术和方法/经济学实验室技术和方法/统计学和数值数据肥胖症/超声检查俄亥俄心室功能左/生理学人类

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Assessment of the ability of the topical skin protectant (TSP) to protect against contact dermatitis to urushiol (rhus) antigen

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American Journal of Contact Dermatitis 1999年第4期10卷 190-197页

作者： Vidmar, Dennis A. Iwane, Marika K. Dept. Mil. Emergency Med. Dermatol. Uniformed Services University Bethesda MD 20814-4799 4301 Jones Bridge Rd United States

Background: Military personnel have a need for effective protection against cutaneous exposure to chemical warfare agents (CWA). Topical Skin Protectant (TSP) is being developed to supplement chemical warfare protective garments. TSP protects against CWA exposure in animals, but does it work for humans? Because humans should not be tested with live CWA, urushiol (poison ivy) extract was used as a surrogate substance in place of CWA for human efficacy testing of TSP. Objective: Determine whether TSP protects human skin against experimentally-induced urushiol dermatitis. Methods: Open urushiol patch testing of 50 rhus-sensitive subjects comparing the 96-hour dermatitis severity scores between TSP protected and TSP unprotected sites. There were 4 paired sites (i.e., protected versus unprotected) per subject. Test sites were scored using a 9-point dermatitis scale of 0.0 to 4.0 (using 0.5 increments). Results: Analysis of variance of the dermatitis scores from 192 paired sites on 48 evaluable subjects showed that TSP protected sites had mean dermatitis scores about 2 points lower than TSP unprotected sites (P < .001). Conclusion: Although this study does not provide direct scientific evidence that TSP protects humans against the percutaneous absorption of CWA, it does provide circumstantial evidence that this is the case. The fact that TSP is so highly effective against a lipophilic substance like urushiol and that most common vesicant CWAs are lipophilic and are weaponized in oleaginous vehicles, makes the effectiveness of TSP in preventing absorption and dermatitis from CWA seem likely.

关键词：变应原/免疫学变应原/药理学抗原/诊断应用抗原/免疫学儿茶酚类/免疫学儿茶酚类/药理学化学战/预防和控制皮炎变应性接触性/诊断皮炎变应性接触性/药物疗法皮炎变应性接触性/免疫学氟碳化合物/投药和剂量模型生物学斑片试验预防和防护用药/投药和剂量敏感性与特异性治疗结果青少年成年人女(雌)性人类男(雄)性中年人

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