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Planning for mass civilian casualties overseas: IMSuRT-International Medical/Surgical Response Teams.

The increased likelihood of mass casualties involving Americans living abroad has prompted the development of a mobile, civilian medical and surgical unit available for rapid deployment overseas. Using past experience derived from the National Disaster Medical Service, and from recent rescue efforts following the African embassy bombings in 1998, an International Medical-Surgical Response Team was developed. Organized under the Department of Homeland Security, it is staffed by civilian professionals from medical and bioengineering fields. Initial deployments to the World Trade Center (2001) and Guam (2002) have shown the ability to rapidly mobilize appropriate manpower and equipment to a mass casualty site, whether domestic or international. The goals of this organization are to work in cooperation with local authorities at the mass casualty site to provide rapid assessment and medical stabilization of injured persons. When the mass casualty is overseas, rapid evacuation of casualties is accomplished by the responding military air evacuation service.

Disaster Planning↗

Comminuted talar neck fractures: a mechanical comparison of fixation techniques.

OBJECTIVE: To compare the mechanical performance of 3 fixation techniques for comminuted talar neck fractures. DESIGN: In vitro biomechanical study. SETTING: Bioengineering research laboratory. PARTICIPANTS: Thirty previously frozen human cadaveric tali were osteotomized across the talar neck. A wedge of bone 2 cm long and extending 50% of the medial to lateral and superior to inferior dimension of the talus was removed to create an unstable, comminuted fracture. INTERVENTION: The specimens were randomized to one of 3 fixation groups. The first group was fixed with 3 anterior-to-posterior screws. The second group was fixed with 2 cannulated screws inserted from posterior to anterior. The third group was fixed with 1 screw from anterior to posterior and a medially applied blade plate. Specimens were embedded in acrylic cement and mounted on an Instron mechanical testing machine. Loading was applied in the dorsal-medial direction to failure. MAIN OUTCOME MEASURES: For each specimen, the load-displacement curve, yield point, and 3 mm displacement point were recorded in response to controlled dorsal-medial loading to failure. Stiffness was calculated as the linear portion of the slope of the load (kN) versus displacement (mm) curve. Statistical analysis of the data was conducted using analysis of variance. RESULTS: The mean yield point of each of the fixation techniques tested exceeded 1.4 kN. No statistically significant difference was found between the fixation methods, even when variations in age and sex were considered. CONCLUSIONS: The mean yield point of the fixation techniques tested exceeds the theoretical stress across the talar neck during active motion. Anterior plate fixation provided equivalent stability to posterior screw fixation.

Adult↗

Therapeutic interventions targeted at the augmentation of reverse cholesterol transport.

PURPOSE OF REVIEW: Serum high-density lipoproteins (HDLs) and reverse cholesterol transport (RCT) are important therapeutic targets in the management of atherosclerotic disease. This review summarizes the pathway of RCT and the currently available means by which investigators are attempting to modulate HDL levels and increase rates of RCT. RECENT FINDINGS: Low levels of HDL are commonly encountered in patients with atherosclerotic disease. HDLs mediate a substantial number of antiatherogenic effects along blood vessel walls. One of the most important of these antiatherogenic mechanisms is RCT, a series of reactions by which HDL is able to facilitate the net translocation of cholesterol from peripheral cells to the liver for excretion. There is scientific evidence supporting the concept of RCT in both animals and humans. To facilitate RCT, it is important that therapeutic effort be made to raise serum levels of HDL. Statins, fibrates, niacin, thiazolidinediones, and various combinations of these drugs all raise HDL levels. However, in many high-risk patients with established atherosclerotic disease, the elevations in HDL achieved with these medications are frequently inadequate. Newer agents designed to raise HDL and promote RCT are currently being developed, including infusible bioengineered HDL, edible HDL composed of D-amino acids, and agents capable of inhibiting cholesterol ester transfer protein, among others. SUMMARY: Established therapies for raising HDL can be effective either as monotherapy or when used in combination. Newer strategies are being developed to exploit more specifically the capacity of HDL to drive RCT and either prevent or reverse the course of atherosclerotic disease.

Apolipoprotein A-I↗

Contribution to the theory of prosthetic vision.

By way of extracellular, electrical stimulation of the visual pathway, the various approaches to vision prosthesis aim to provide crude, patterned vision to individuals with profound blindness. Common to all approaches is the implantable electrode array and the rendering of phosphenes-the actuated percepts occupying the visual field of the implantee. Thus prosthetic vision may be simulated, and underlying theories as to how to render it efficacious developed. We review the field of simulated prosthetic vision. Furthermore, with retinal prosthesis in mind, we suggest a revised approach-an approach with regard to sampling theory, the vertebrate central visual pathway, and eye movements. The parallel development of prosthetic vision theory, explored via simulation and bioengineering issues surrounding neurostimulator design and implantation has bearing on the success of clinical trials by numerous groups in coming years.

Biomedical Engineering↗

Toward human organ printing: Charleston Bioprinting Symposium.

The First Annual Charleston Bioprinting Symposium was organized by the Bioprinting Research Center of the Medical University of South Carolina (MUSC) and convened July 21, 2006, in Charleston, South Carolina. In broad terms, bioprinting is the application of rapid prototyping technology to the biomedical field. More specifically, it is defined as the layer by layer deposition of biologically relevant material. The 2006 Symposium included four sessions: Computer-aided design and Bioprinting, Bioprinting Technologies; Hydrogel for Bioprinting and, finally, a special session devoted to ongoing research projects at the MUSC Bioprinting Research Center. The Symposium highlight was the presentation of the multidisciplinary Charleston Bioengineered Kidney Project. This symposium demonstrated that bioprinting or robotic biofabrication is one of the most exciting and fast-emerging branches in the tissue engineering field. Robotic biofabrication will eventually lead to industrial production of living human organs suitable for clinical transplantation. The symposium demonstrated that although there are still many technological challenges, organ printing is a rapidly evolving feasible technology.

Artificial Organs↗

Emerging technologies in transdermal therapeutics.

Until very recently, the only drugs that could permeate transdermally were those possessing a very narrow and specific combination of physicochemical properties. However, rapid advances in bioengineering have led to the emergence of various new "active" enhancement technologies designed to transiently circumvent the barrier function of the stratum corneum. These novel systems, using iontophoresis, sonophoresis, electroporation, or microneedle arrays, will greatly expand the range of drugs that can be delivered transdermally. Crucially, the delivery of macromolecules will become possible and the transdermal flux of other molecules could be enhanced by several orders of magnitude. This article sequentially reviews the basis of each of the new enhancement techniques and discusses how these emerging technologies will influence transdermal therapy in the coming years.

Administration, Cutaneous↗

Auricular reconstruction: an update.

PURPOSE OF REVIEW: One of the greatest challenges in facial plastic surgery is total auricular reconstruction. The ability to construct a fully satisfactory complete external ear has for centuries been an elusive goal. With advancing standards and expectations in plastic surgery, greater focus is being directed to this arena of reconstruction as well. RECENT FINDINGS: With advances both in surgical technique and biotechnology, an expanding range of options is available to the reconstructive surgeon who is willing to take on this still formidable task. While progress continues to be made in the detailing of costal cartilage grafts and soft-tissue rearrangement, it is also being made with the use of alloplastic implants and prostheses. The most promising field of advances, with the hope of eventual clinical utility, lies in the realm of bioengineering with cultured cartilage. SUMMARY: Review of the literature over the past year reveals several reports describing advances made in the development of cultured chondrocytes with attempts to direct special shape to the manufactured neocartilage. Though advances continue to be made, actual clinical applicability of this technology is still insufficient while expectation continues that this will eventually become integral to total auricular reconstruction.

Cartilage↗

Pediatric catheter interventions: a year in review 2004-2005.

PURPOSE OF THE REVIEW: The fields of pediatric and congenital cardiac interventions continue to expand at a rapid pace. The last few years have witnessed a tremendous explosion in procedures such as the transcatheter closure of secundum atrial septal defects, patent foramen ovale, patent ductus arteriosus, stent placement for pulmonary artery stenosis, and coarctation of the aorta. The purpose of this review is to highlight important publications in the last year and the direction the field is taking. RECENT FINDINGS: Research data over the last year has concentrated on six main themes: (a) mid-to-long-term data for device closure of atrial septal defects, the incidence of late cardiac erosions, thrombus formation and heart block; (b) the transcatheter closure of muscular ventricular septal defects; (c) the transcatheter closure of perimembranous ventricular septal defects; (d) the placement of bioprosthetic valves in the pulmonary and aortic positions; (e) the 'hybrid' approach that combines surgical and interventional techniques in the management of various congenital cardiac defects; and (f) fetal interventions. SUMMARY: This review outlines the key data presented in the literature involving interventional cardiology for pediatric and congenital cardiac defects over the last year. It illustrates that in close collaboration with industry, together with bioengineers and cardiothoracic surgeons, adult cardiac interventionists and perinatologists should continue to expand the role of pediatric catheter interventions. Fetal interventions have the potential to alter the natural history of abnormal cardiac development.

Adult↗

Recent developments in tissue engineering and regenerative medicine.

PURPOSE OF REVIEW: Currently, patients suffering from diseased and injured organs are treated with transplanted organs or cells. There is, however, a severe shortage of donor tissues and organs that is worsening yearly given the aging population. This paper reviews recent advances that have occurred in regenerative medicine and describes applications of new technologies to treat diseased or damaged organs and tissues. RECENT FINDINGS: Most current strategies for tissue engineering depend upon a sample of autologous cells from the diseased organ of the patient. Biopsies from patients with extensive end-stage organ failure, however, may not yield enough normal cells. In these situations, stem cells are envisioned as being an alternative source. Stem cells can be derived from discarded human embryos (human embryonic stem cells), from fetal tissue or from adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially limitless source of cells for tissue engineering applications. SUMMARY: Increasingly, scientists in the fields of regenerative medicine and tissue engineering have applied the principles of cell transplantation, material science and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues.

Animals↗

Recent applications of regenerative medicine to urologic structures and related tissues.

PURPOSE OF REVIEW: A severe shortage of donor tissues and organs exists, which is worsening yearly given the aging population. Currently, patients suffering from diseased and injured organs are treated with transplanted organs or cells. This paper reviews recent advances that have occurred in regenerative medicine and describes application of new technologies to treat diseased or damaged organs and tissues. RECENT FINDINGS: Although most current strategies for tissue engineering depend upon a sample of autologous cells from the diseased organ of the patient, biopsies from patients with extensive end-stage organ failure may not yield enough normal cells. In these situations, stem cells are envisioned as being an alternative source. Stem cells can be derived from discarded human embryos (human embryonic stem cells), from fetal tissue, or from adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially limitless source of cells for tissue engineering applications. SUMMARY: Recently, scientists in the fields of regenerative medicine and tissue engineering have applied the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues.

Animals↗

The efficacy of Apligraf in the treatment of diabetic foot ulcers.

Diabetic foot ulcerations can be a devastating complication of diabetes, causing prolonged hospitalization and significant morbidity. Previously identified risk factors include peripheral neuropathy, foot deformities, and poor wound healing due to an altered wound environment. Despite appropriate treatment, many diabetic ulcers fail to heal. Bioengineered tissue, such as Apligraf (Graftskin; Organogenesis Inc., Canton, Mass.), has been effectively and safely used to increase the incidence of complete wound closure and decrease the healing time. Studies have demonstrated that Apligraf works through the delivery of growth factors and cytokines to the chronic wound environment.

Biocompatible Materials↗

Clinical approach to wounds: débridement and wound bed preparation including the use of dressings and wound-healing adjuvants.

This is a clinical review of current techniques in wound bed preparation found to be effective in assisting the wound-healing process. The process begins with the identification of a correct diagnosis of the wound's etiology and continues with optimizing the patient's medical condition, including blood flow to the wound site. Débridement as the basis of most wound-healing strategies is then emphasized. Various débridement techniques, including surgery, topical agents, and biosurgery, are thoroughly discussed and illustrated. Wound dressings, including the use of negative pressure wound therapy, are then reviewed. To properly determine the timing of advance therapeutic intervention, the wound-healing progress needs to be monitored carefully with weekly measurements. A reduction in wound area of 10 to 15 percent per week represents normal healing and does not mandate a change in the current wound-healing strategy. However, if this level of wound area reduction is not met consistently on a weekly basis, then alternative healing interventions should be considered. There is a growing body of evidence that can provide guidance on the appropriate use of such adjuvants in the problem wound. Several adjuvants are discussed, including growth factor, bioengineered tissues, and hyperbaric medicine.

Acute Disease↗

A review of surgical simulation with attention to validation methodology.

The use of simulation technology for teaching and evaluating surgical skills has gained considerable attention in recent years. This is driven by interest in quality of care, concerns over increasing operative complexity, constraints on the use of animal models, limited available patient material, medicolegal pressures, and fiscal mandates for cost-effective performance. Traditional mechanical models are yielding to techniques dependent on electronic technology, including virtual reality. Data to support the validity of simulation techniques for surgical training, assessment, and certification represent only a fraction of the literature available on the subject. Literature searches were conducted in MEDLINE and ERIC, covering the period from 1966 to the present. The electronic and bioengineering literature was not surveyed due to the extensive literature on technology development, distinct from assessment of context specific validity. The search results and the bibliographies of key review articles were examined to identify articles that contained original data, measured performance between cohorts, defined performance measures, and described a standard against which performance was compared. Most of the literature pertaining to simulation techniques for surgical training has been published within the past 5 years and consist of review, opinion, and feasibility articles. There is an emerging body of evidence to establish the validity of simulation techniques for assessing surgical skills. Further refinement of simulation techniques, identification of specific performance measures, longitudinal evaluations, and comparison to practice outcomes are still needed to establish the validity and the value of surgical simulation for teaching and assessing surgical skills prior to considering implementation for certification purposes.

Animals↗

Toward development of imaging modalities for islets after transplantation: insights from the National Institutes of Health Workshop on Beta Cell Imaging.

BACKGROUND: Pancreatic islet transplantation can provide insulin independence and near normal glucose control in selected patients with type 1 diabetes mellitus. However, in most cases, achieving insulin independence necessitates the use of at least two donor pancreases per recipient and the rate of insulin independence may decline after transplantation. To better understand the fate of transplanted islets and the relationship between transplanted islet mass, graft function, and overall glucose homeostasis, an accurate and reproducible method of imaging islets in vivo is needed. METHODS: Recent advances in noninvasive imaging techniques such as magnetic resonance imaging, positron emission tomography, and other imaging modalities show great promise as potential tools to monitor islet number, mass, and function in the clinical setting. A recent international workshop, "Imaging the Pancreatic Beta Cell," sponsored by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Juvenile Diabetes Research Foundation International focused on these emerging efforts to develop novel ways of imaging pancreatic beta cells in vivo. RESULTS: Potential clinically applicable techniques include the use of directed magnetic resonance contrast agents such as lanthanides (Ln(3+)) and manganese (Mn(2+)) or magnetic resonance imaging probes such as superparamagnetic iron oxide nanoparticles. Potential techniques for positron emission tomography imaging include the use of beta cell-specific antibodies, or pharmacologic agents such as glyburide analogs, or d-mannoheptulose. Optical imaging techniques are also being used to evaluate various aspects of beta cell metabolism including intracellular Ca(2+) flux, glucokinase activity, and insulin granular exocytosis. CONCLUSIONS: The consensus among investigators at the imaging workshop was that an accurate and reproducible in vivo measure of functional islet mass is critically needed to further the strides that have been made in both islet transplantation and diabetes research as a whole. Such measures would potentially allow the assessment of islet engraftment and the early recognition of graft loss, leading to greater improvements in islet graft survival and function.

Diagnostic Imaging↗

The problem of evaluating in situ pinning of slipped capital femoral epiphysis: an experimental model and a review of 63 consecutive cases.

Over a 3-year follow-up period, 63 hips (in 49 patients) that were pinned as treatment for slipped capital femoral epiphysis were examined and evaluated. A 36.8% incidence of unsuspected pin penetration was discovered. Four types of experimental models representing different degrees of severity of slipped capital femoral epiphysis were designed and manufactured in the bioengineering laboratory. In situ pinning was performed on each model. An extensive series of controlled test films on the models indicated the difficulty of accurately determining the true position of the pins with conventional roentgenographic views. Subsequent fluoroscopic analysis revealed a verifiable correlation between the limited visualization of conventional X-ray analysis following the pinning of a slipped capital femoral epiphysis and unrecognized pin penetration.

Bone Nails↗

Expression of human beta defensin 4 in genetically modified keratinocytes enhances antimicrobial activity.

Defensins are cationic peptides of the innate host defense system with antimicrobial activity against many of the microorganisms commonly found in burn units. Beta defensins are variably expressed in the epithelia of skin and other organs. Human beta defensin 4 reportedly has antimicrobial activity against Pseudomonas aeruginosa and is not normally expressed in intact skin. Genetic modification was used to ectopically express human beta defensin 4 in cultured primary epidermal keratinocytes. Keratinocytes expressing human beta defensin 4 showed significantly elevated antimicrobial activity against clinically-isolated P. aeruginosa compared with controls. These results suggest that genetic modification of keratinocytes can increase their resistance to microbial contamination. Bioengineered skin replacements containing human beta defensin 4-modified keratinocytes may be useful for transplantation to contaminated burn wounds.

Adult↗

Construction and characterization of deletion mutants of pseudorabies virus: a new generation of 'live' vaccines.

Various deletions were introduced into a cloned subgenomic fragment (BamHI-7), located in the unique short (US) region of the DNA from the virulent Northern Ireland Aujeszky-3 (NIA-3) strain of pseudorabies virus (PRV). In the cloned HindIII-B fragment, the MluI-BglII fragment was replaced by different MluI-BglII fragments of the deleted BamHI-7 clones. Transfection of the deleted HindIII-B fragments together with the HindIII-A fragment of either the NIA-3 or the non-virulent NIA-4 strain yielded replication-competent deletion mutants. The region in US in which sequences were deleted specified several mRNAs. Some of the mRNAs present in cells infected with NIA-3 were absent from cells infected with the deletion mutants, whereas other differently sized mRNAs were generated. The mutants were examined with respect to their biological properties in cell culture, mice and pigs. The results showed that the type of cytopathic effect induced in cell culture seemed to be determined by the UL region, using the mean time to death in mice as a parameter, markers for virulence were present in the US and UL regions and the introduction of deletions in US strongly reduced the virulence of PRV for pigs. Despite the impaired capacity of the deletion mutants to induce high titres of neutralizing antibodies in the serum, inoculation with mutants derived from NIA-3 prevented clinical disease in pigs upon challenge with the virulent parent strain. These deletion mutants provide a good basis for the production of bioengineered live PRV vaccines.

Animals↗

Asymmetric cell kinetics genes: the key to expansion of adult stem cells in culture.

A singular challenge in stem cell research today is the expansion and propagation of functional adult stem cells. Unlike embryonic stem cells, which are immortal in culture, adult stem cells are notorious for the difficulty encountered when attempts are made to expand them in culture. One overlooked reason for this difficulty may be the inherent asymmetric cell kinetics of stem cells in postnatal somatic tissues. Senescence is the expected fate of a culture whose growth depends on adult stem cells that divide with asymmetric cell kinetics. Therefore, the bioengineering of strategies to expand adult stem cells in culture requires knowledge of cellular mechanisms that control asymmetric cell kinetics. The properties of several genes recently implicated to function in a cellular pathway(s) that regulates asymmetric cell kinetics are discussed. Understanding the function of these genes in asymmetric cell kinetics mechanisms may be the key that unlocks the adult stem cell expansion problem.

Adult↗