Improved hemostasis in hemophilia mice by means of an engineered factor Va mutant.

BACKGROUND: Factor (F)VIIa-based bypassing not always provides sufficient hemostasis in hemophilia. OBJECTIVES: To investigate the potential of engineered activated factor V (FVa) variants as bypassing agents in hemophilia A. METHODS: Activity of FVa variants was studied in vitro using prothrombinase assays with purified components and in FV- and FVIII-deficient plasma using clotting and thrombin generation assays. In vivo bleed reduction after the tail clip was studied in hemophilia A mice. RESULTS AND CONCLUSIONS: FVa mutations included a disulfide bond connecting the A2 and A3 domains and ones that rendered FVa resistant to inactivation by activated protein C (APC). '(super) FVa,' a combination of the A2-A3 disulfide (A2-SS-A3) to stabilize FVa and of APC-cleavage site mutations (Arg506/306/679Gln), had enhanced specific activity and complete APC resistance compared with wild-type FVa, FVL eiden (Arg506Gln), or FVaL eiden (A2-SS-A3). Furthermore, (super) FVa potently increased thrombin generation in vitro in FVIII-deficient plasma. In vivo, (super) FVa reduced bleeding in FVIII-deficient mice more effectively than wild-type FVa. Low-dose (super) FVa, but not wild-type FVa, decreased early blood loss during the first 10 min by more than two-fold compared with saline and provided bleed protection for the majority of mice, similar to treatments with FVIII. During the second 10 min after tail cut, (super) FVa at high dose, but not wild-type FVa, effectively reduced bleeding. These findings suggest that (super) FVa enhances not only clot formation but also clot stabilization. Thus, (super) FVa efficiently improved hemostasis in hemophilia in vitro and in vivo and may have potential therapeutic benefits as a novel bypassing agent in hemophilia.

The effect of 10 : 1 compression and soft copy interpretation on the chest radiographs of premature neonates with reference to their possible application in teleradiology.

The aim of the study was to assess the potential application of teleradiology in the neonatal intensive care unit (NICU) by ascertaining whether any decrease in conspicuity of anatomic detail or interventional devices in the chest radiographs of premature infants is caused by picture archiving and communication system (PACS)-based soft copy interpretation of 10 : 1 compressed images. One hundred digital chest radiographs of low-birthweight infants were obtained in the NICU using a storage phosphor system. Laser-printed images were interpreted and the data set for each radiograph was then irreversibly compressed by a 10 : 1 ratio. Four radiologists with extensive PACS experience used a five-point grading system to score laser-printed hard copy images for the visibility of six parameters of anatomic landmarks and interventional devices in the chest. Compressed soft copy images displayed on 2K PACS workstation were subsequently scored using the same approach. Statistical manipulation demonstrated no loss of anatomic detail in five of the six parameters scored, with minimal difference in one landmark, the retrocardiac lung assessment. While further study is required to assess the clinical impact of the variance noted when evaluating lung parameters, the preservation or improvement of information in the remaining parameters following irreversible compression and soft copy interpretation is promising for the potential use of teleradiology in this population.

Operation Joint Endeavor in Bosnia: telemedicine systems and case reports.

OBJECTIVE: For the last several years the U.S. Department of Defense (DoD) has operated a telemedicine test bed at the U.S. Army Medical Research and Material Command's Medical Advanced Technology Management Office. The goal of this test bed is to reengineer the military health service system from the most forward deployed forces to tertiary care teaching medical centers within the United States by exploiting emerging telemedicine technologies. METHODS: The test bed has conducted numerous proof-of-concept telemedicine demonstrations as part of military exercises and in support of real-world troop deployments. The most ambitious of those demonstrations is Primetime III, an ongoing effort to provide telemedicine and other advanced technology support to medical units supporting Operation Joint Endeavor in Bosnia. RESULTS: Several of the first instances of the clinical use of the Primetime III systems are presented as case reports in this paper. These reports demonstrate capabilities and limitations of telemedicine. CONCLUSION: The Primetime III system demonstrates the technical ability to provide current telecommunications capabilities to medical units stationed in the remote, austere, difficult-to-serve environment of Bosnia. Telemedicine capabilities cannot be used without adequate training, operations, and sustainment support. Video consultations have eliminated the need for some evacuations. The system has successfully augmented the clinical capability of physicians assigned to these medical units. Fullest clinical utilization of telemedicine technologies requires adjustment of conventional clinical practice patterns.

Evaluation of the Cavitron Spirometric Computer for accuracy in clinical screening spirometry.

Ten healthy male cardiopulmonary technicians, 10 aircrew members, and 10 patients performed a series of pulmonary function studies to compare the Cavitron Spirometric Computer to the conventional water-sealed Collins 13.5-/spirometer. A total of 50 studies were performed on the spirometers individually and then with the spirometers linked in-line. The Cavitron FVC averaged 6% less, the FEV1--7% less, and the FEF 25-75%--11.6% less than comparable measurements from the Collins spirometer. Since these difference are within the suggested guidelines for screening studies, the Cavitron Spirometric Computer is acceptable for use in clinical screening spirometry.