Liposome-encapsulated hemoglobin: a synthetic red cell.

Liposome-encapsulated hemoglobin (LEH) is being developed at the Naval Research Laboratory as a universally transfusable oxygen-carrying blood replacement. A chemical engineering scale-up feasibility study has been completed recently. We report here the development of an encapsulation method which produces liters of phospholipid/cholesterol liposomes containing at least 16 g% hemoglobin in a few hours. The 0.2 micron liposomes are produced with a Microfluidizer TM (Microfluidics Corp., Newton, MA) adapted for this purpose, and then washed and sterile filtered using a Pellicon (Millipore, Bedford, MA) tangential flow filtration device. Previously, production limitations and lack of sterility have been serious barriers to toxicity testing for all the researchers engaged in related investigations. The biophysical properties of the LEH thus produced are ideal for use as a blood substitute, resembling those of red blood cells. The oxygen-binding affinity of LEH can be maintained at the level of fresh whole blood for many weeks by co-encapsulation of pyridoxal-5-phosphate. The circulation persistence time of liposomes is a function of the type of phospholipid. We have developed a formulation which has a circulation persistence time of 15-20 hours. The LEH oxygen binding characteristics, circulation half-life and its lipid composition dependence, scale-up preparation method, and a sterilization method are presented.

Endoleak after aortic stent graft repair: diagnosis by color duplex ultrasound scan versus computed tomography scan.

PURPOSE: The purpose of this study was to compare the accuracy of a color duplex ultrasound scan (CDU) to a computerized axial tomography scan (CT) in the diagnosis of endoleaks after stent graft repair of abdominal aortic aneurysms. METHODS: The Endovascular Aneurysm Clinical Trial Core Laboratory records were reviewed from 117 concurrent CDU and CT studies that were performed in 79 patients who were implanted with the Endovascular Technologies stent graft device between December 1995 and January 1997. All of the studies were interpreted by the Core Laboratory as having the presence or the absence of an endoleak or as being indeterminate because of technical factors. Of the 117 videotaped CDU studies available for reexamination, 100 were reassessed for technical adequacy on the basis of the following criteria: a satisfactory imaging of the aneurysm sac and of the stent graft with gray scale, and both color and spectral Doppler scan evaluation for endoleak outside the endograft and within the aneurysm sac. RESULTS: Of the 117 studies, 103 CDUs (88%) and 114 CTs (97%) were recorded as having the presence or the absence of an endoleak and 14 CDUs (12%) and 3 CTs (3%) were indeterminate. For the studies that were recorded to have the presence or the absence of an endoleak, the sensitivity, the specificity, the positive and the negative predictive values, and the accuracy of CDUs as compared with CTs were 97%, 74%, 66%, 98%, and 82%, respectively. Of the 100 CDU videotaped studies available for review, the following results were seen: (1) 93 CDUs had satisfactory B-mode images, (2) 76 had satisfactory color Doppler scan images to evaluate for endoleaks, (3) 55 had color Doppler scan assessment of the entire abdominal aortic aneurysm sac for endoleak, and (4) 27 had spectral Doppler scan waveform confirmation of suspected endoleaks. Only 19 CDU studies (19%) with all 4 criteria for complete assessment of endoleak were performed. CONCLUSION: Although most of the CDU studies were technically suboptimal, the CDUs reliably identified endoleaks with an excellent sensitivity and a negative predictive value as compared with CT scans.