A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile conditions had rupture strengths greater than 2000 millimeters of mercury, suture retention strengths of up to 90 grams, and collagen contents of up to 50 percent. Cultured vessels also showed contractile responses to pharmacological agents and contained smooth muscle cells that displayed markers of differentiation such as calponin and myosin heavy chains. Tissue-engineered arteries were implanted in miniature swine, with patency documented up to 24 days by digital angiography. (+info)
Care and feeding of a staff for filmless radiology.
Texas Children's Hospital, a definitive care pediatric hospital located in the Texas Medical Center, has been constructing a large-scale picture archival and communications system (PACS) including ultrasound (US), computed tomography (CT), magnetic resonance (MR), and computed radiography (CR). Developing staffing adequate to meet the demands of filmless radiology operations has been a continuous challenge. Overall guidance for the PACS effort is provided by a hospital-level PACS Committee, a department-level PACS Steering Committee, and an Operations Committee. Operational Subcommittees have been formed to address service-specific implementation, such as the Emergency Center Operations Subcommittee. These committees include membership by those affected by the change, as well as those effecting the change. Initially, personnel resources for PACS were provided through additional duties of existing imaging service personnel. As the PACS effort became more complex, full-time positions were created, including a PACS Coordinator, a PACS Analyst, and a Digital Imaging Assistant. Each position requires a job description, qualifications, and personnel development plans that are difficult to anticipate in an evolving PACS implementation. These positions have been augmented by temporary full-time assignments, position reclassifications, and cross-training of other imaging personnel. Imaging personnel are assisted by other hospital personnel from Biomedical Engineering and Information Services. Ultimately, the PACS staff grows to include all those who must operate the PACS equipment in the normal course of their duties. The effectiveness of the PACS staff is limited by their level of their expertise. This report discusses our methods to obtain training from outside our institution and to develop, conduct, and document standardized in-house training. We describe some of the products of this work, including policies and procedures, clinical competency criteria, PACS inservice topics, and an informal PACS newsletter. As the PACS system software and hardware changes, and as our implementation grows, these products must to be revised and training must be repeated. (+info)
Reengineering the picture archiving and communication system (PACS) process for digital imaging networks PACS.
Prior to June 1997, military picture archiving and communications systems (PACS) were planned, procured, and installed with key decisions on the system, equipment, and even funding sources made through a research and development office called Medical Diagnostic Imaging Systems (MDIS). Beginning in June 1997, the Joint Imaging Technology Project Office (JITPO) initiated a collaborative and consultative process for planning and implementing PACS into military treatment facilities through a new Department of Defense (DoD) contract vehicle called digital imaging networks (DIN)-PACS. The JITPO reengineered this process incorporating multiple organizations and politics. The reengineered PACS process administered through the JITPO transformed the decision process and accountability from a single office to a consultative method that increased end-user knowledge, responsibility, and ownership in PACS. The JITPO continues to provide information and services that assist multiple groups and users in rendering PACS planning and implementation decisions. Local site project managers are involved from the outset and this end-user collaboration has made the sometimes difficult transition to PACS an easier and more acceptable process for all involved. Corporately, this process saved DoD sites millions by having PACS plans developed within the government and proposed to vendors second, and then having vendors respond specifically to those plans. The integrity and efficiency of the process have reduced the opportunity for implementing nonstandard systems while sharing resources and reducing wasted government dollars. This presentation will describe the chronology of changes, encountered obstacles, and lessons learned within the reengineering of the PACS process for DIN-PACS. (+info)
Tissue engineering of a bioartificial renal tubule assist device: in vitro transport and metabolic characteristics.
BACKGROUND: Current renal substitution therapy for acute or chronic renal failure with hemodialysis or hemofiltration is life sustaining, but continues to have unacceptably high morbidity and mortality rates. This therapy is not complete renal replacement therapy because it does not provide active transport nor metabolic and endocrinologic functions of the kidney, which are located predominantly in the tubular elements of the kidney. METHODS: To optimize renal substitution therapy, a bioartificial renal tubule assist device (RAD) was developed and tested in vitro for a variety of differentiated tubular functions. High-flux hollow-fiber hemofiltration cartridges with membrane surface areas of 97 cm2 or 0. 4 m2 were used as tubular scaffolds. Porcine renal proximal tubule cells were seeded into the intraluminal spaces of the hollow fibers, which were pretreated with a synthetic extracellular matrix protein. Attached cells were expanded in the cartridge as a bioreactor system to produce confluent monolayers containing up to 1.5 x 109 cells (3. 5 x 105 cells/cm2). Near confluency was achieved along the entire membrane surface, with recovery rates for perfused inulin exceeding 97 and 95% in the smaller and larger units, respectively, compared with less than 60% recovery in noncell units. RESULTS: A single-pass perfusion system was used to assess transport characteristics of the RADs. Vectorial fluid transport from intraluminal space to antiluminal space was demonstrated and was significantly increased with the addition of albumin to the antiluminal side and inhibited by the addition of ouabain, a specific inhibitor of Na+,K+-ATPase. Other transport activities were also observed in these devices and included active bicarbonate transport, which was decreased with acetazolamide, a carbonic anhydrase inhibitor, active glucose transport, which was suppressed with phlorizin, a specific inhibitor of the sodium-dependent glucose transporters, and para-aminohippurate (PAH) secretion, which was diminished with the anion transport inhibitor probenecid. A variety of differentiated metabolic functions was also demonstrated in the RAD. Intraluminal glutathione breakdown and its constituent amino acid uptake were suppressed with the irreversible inhibitor of gamma-glutamyl transpeptidase acivicin; ammonia production was present and incremented with declines in perfusion pH. Finally, endocrinological activity with conversion of 25-hydroxy(OH)-vitamin D3 to 1,25-(OH)2 vitD3 was demonstrated in the RAD. This conversion activity was up-regulated with parathyroid hormone and down-regulated with increasing inorganic phosphate levels, which are well-defined physiological regulators of this process in vivo. CONCLUSIONS: These results clearly demonstrate the successful tissue engineering of a bioartificial RAD that possesses critical differentiated transport, and improves metabolic and endocrinological functions of the kidney. This device, when placed in series with conventional hemofiltration therapy, may provide incremental renal replacement support and potentially may decrease the high morbidity and mortality rates observed in patients with renal failure. (+info)
Selective removal of alloreactive cells from haematopoietic stem cell grafts: graft engineering for GVHD prophylaxis.
One of the main goals in allogeneic bone marrow transplantation is the abrogation of graft-versus-host disease with the preservation of antileukaemia and antiviral activity. We have established a novel system for the selective removal of alloreactive lymphocytes from donor grafts while retaining an effective allogeneic response to third-party stimulator cells. Initial feasibility studies were done with unrelated HLA-mismatched pairs and then extended into the matched setting. Mononuclear cells from HLA-matched donors were cocultured with irradiated recipient cells prestimulated with cytokines (gamma-IFN and TNF-alpha) in a modified mixed lymphocyte culture (MLC). Alloreactive donor lymphocytes were identified by expression of CD69, an early activation marker and selectively removed by paramagnetic bead sorting. The remaining 'non-alloreactive' lymphocytes were tested in proliferative assays against the original matched recipient and to a third-party donor. A mean depletion of proliferative capacity to 11.5 +/- 9.9% of the original matched recipient response was achieved while the residual third-party response was largely preserved at 77.8 +/- 20.9% which should translate into improved immune reconstitution and preservation of antiviral activity. The non-alloreactive lymphocytes could also possess functional antileukaemia activity. Moreover, the alloreactive cells are easily recoverable in this selective T cell depletion strategy for cryopreservation and ready for immediate access as therapeutic donor lymphocyte infusions in cases of frank relapse post transplant. (+info)
Informatics at the National Institutes of Health: a call to action.
Biomedical informatics, imaging, and engineering are major forces driving the knowledge revolutions that are shaping the agendas for biomedical research and clinical medicine in the 21st century. These disciplines produce the tools and techniques to advance biomedical research, and continually feed new technologies and procedures into clinical medicine. To sustain this force, an increased investment is needed in the physics, biomedical science, engineering, mathematics, information science, and computer science undergirding biomedical informatics, engineering, and imaging. This investment should be made primarily through the National Institutes of Health (NIH). However, the NIH is not structured to support such disciplines as biomedical informatics, engineering, and imaging that cross boundaries between disease- and organ-oriented institutes. The solution to this dilemma is the creation of a new institute or center at the NIH devoted to biomedical imaging, engineering, and informatics. Bills are being introduced into the 106th Congress to authorize such an entity. The pathway is long and arduous, from the introduction of bills in the House and Senate to the realization of new opportunities for biomedical informatics, engineering, and imaging at the NIH. There are many opportunities for medical informaticians to contribute to this realization. (+info)
Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies.
The objective of this study was to establish a three-dimensional (3-D) in vitro model system of cardiac muscle for electrophysiological studies. Primary neonatal rat ventricular cells containing lower or higher fractions of cardiac myocytes were cultured on polymeric scaffolds in bioreactors to form regular or enriched cardiac muscle constructs, respectively. After 1 wk, all constructs contained a peripheral tissue-like region (50-70 micrometer thick) in which differentiated cardiac myocytes were organized in multiple layers in a 3-D configuration. Indexes of cell size (protein/DNA) and metabolic activity (tetrazolium conversion/DNA) were similar for constructs and neonatal rat ventricles. Electrophysiological studies conducted using a linear array of extracellular electrodes showed that the peripheral region of constructs exhibited relatively homogeneous electrical properties and sustained macroscopically continuous impulse propagation on a centimeter-size scale. Electrophysiological properties of enriched constructs were superior to those of regular constructs but inferior to those of native ventricles. These results demonstrate that 3-D cardiac muscle constructs can be engineered with cardiac-specific structural and electrophysiological properties and used for in vitro impulse propagation studies. (+info)
Amphibian embryos as a model system for organ engineering: in vitro induction and rescue of the heart anlage.
Beating hearts can be induced under in vitro conditions when the dorsal blastopore lip (including the zone of Spemann organizer) is treated with Suramin. In contrast, untreated organizer forms dorsal mesodermal derivatives as notochord and somites. When those in vitro produced heart precursor tissues are transplanted ectopically in the posterior trunk area of early larvae, secondary beating heart structures will be formed. Furthermore, the replacement of the heart primordium of the host embryo by heart tissue induced under in vitro conditions will result in the rescue of the heart anlage. This model could be a valuable tool for the study of the multi-step molecular mechanisms of heart structure induction under in vitro conditions and vasculogenesis after transplantation into the host embryo. (+info)