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A novel system for organ and tissues preservation: the refrigerating hyperbaric chamber.

UNLABELLED: This study was designed to investigate the feasibility of building a simple and inexpensive device to preserve organs or tissues in hyperbaric and hypothermic conditions. METHODS: The device was built on a 40-cm wide, 28-cm long, and 23-cm deep stainless steel chassis. The pressure vessel was built by a 7.8-cm bore stainless steel cylinder put inside another 12-cm cylinder welded together and closed by a steel plate on the top and bottom. The inferior plate was welded, and the superior one was fixed by manual clasp nut. The cooling system is made up of air compressor, condenser, expansion area, and cooling worm that is located between the cylinders. The temperature-controlling device is a computer processor contained in an integrated-circuit chip, with a on-off system to maintain the chamber temperature between 2 degrees to 4 degrees C. The compression of the chamber is performed by lateral coupling with the oxygen cylinder and is maintained at 5.5 absolute atmospheres and controlled by air pressure gauge. The maximal work pressure was evaluated by spreadsheet. Temperature or pressure changes were evaluated by 12- and 24-hour assays. RESULTS: The maximal work pressure permitted was 6.5 absolute atmospheres. Thus, the container was free from danger. The temperature inside the chamber was kept between 2 degrees and 4 degrees C. The production costs of the prototype was US$1000. DISCUSSION: The manufacture of the refrigerating hyperbaric chamber is viable, simple, and inexpensive.

Cold Temperature↗

Transurethral implantation of silicone polymer for stress incontinence: evaluation of a porcine model and mechanism of action in vivo.

OBJECTIVE: To evaluate the anatomical location, histological appearances and mechanism of action of sili-cone polymer (Macroplastique(R)) after transurethral implantation. MATERIALS AND METHODS: An in vivo pig model was developed to investigate the organization of Macroplastique 6 weeks after injection. The results were compared with the immediate appearance of injected Macroplastique in a surgical training device (using isolated pig urethrae) and with the histological appearances of Macroplastique in an explanted human specimen. RESULTS: Macroplastique was subserosal in all specimens; it provoked a marked foreign-body inflammatory reaction, producing firm nodules 6 weeks after implantation. The histological appearances in the in vivo pig model and the human specimen were indistinguishable. CONCLUSIONS: These findings indicate that the mechanism of action of Macroplastique is to augment pressure transmission to the proximal urethra by producing focal but firm expansion of periurethral tissues.

Animals↗

The fibrous capsules around static and dynamic implants: their biochemical, histological, and ultrastructural characteristics.

In this article, we report the findings of a small study comparing the histological, ultrastructural, and biochemical features of fibrous capsules formed around tissue-expanding devices (dynamic implants) and simple prostheses (static implants) in the human. Histologically and biochemically, the dynamic fibrous capsule appears to represent an early phase of scar tissue formation around an expanding foreign body, the dominant feature being increased cellularity caused by myofibroblasts. In view of the marked presence of these contractile elements, it is paradoxical that a lower capsular contracture rate should be reported to occur in breast reconstruction using a temporary expander. This lower rate presumably is because these myofibroblasts undergo modulation once the expansion process has ceased and the final prosthesis is in place. One may also assume that the fibrous capsule would retain features of early scar tissue if the expansion process is maintained indefinitely. This hypothesis can be evaluated by a long-term study in the animal.

Cicatrix↗

Development of Microelectromechanical Systems (MEMS) forceps for intraocular surgery.

AIM: To develop silicon microforceps for intraocular surgery using Microelectromechanical Systems (MEMS) technology, the application of microchip fabrication techniques for the production of controllable three dimensional devices on the micrometre scale. METHODS: Prototype MEMS forceps were designed and manufactured for intraocular surgery. Scanning electron microscopy was used to evaluate device tip construction. Designs using both thermal expansion actuators and conventional mechanical activation were tested in human cadaver eyes and in vivo rabbit eyes to assess functionality in standard vitreoretinal surgery. RESULTS: MEMS forceps were constructed with various tip designs ranging from 100 mum to 2 mm in length. Scanning electron microscopy confirmed accurate construction of micro features such as forceps teeth as small as tens of micrometres. In surgical testing, the silicon forceps tips were effective in surgical manoeuvres, including grasping retinal membranes and excising tissue. The mechanical actuator design on a 20 gauge handle was more operational in the intraocular environment than the thermal expansion actuator design. While handheld operation was possible, the precision of the forceps was best exploited when mounted on a three axis micromanipulator. CONCLUSION: MEMS microforceps are feasible for conventional vitreoretinal surgery, and offer advances in terms of small scale, operating precision, and construction tolerance.

Animals↗

Advances in burn scar reconstruction: the use of tissue expansion.

The use of tissue expansion to facilitate burn scar reconstruction is described. Twelve patients underwent burn scar reconstruction using a total of 42 expanders. Expansion was carried out at two- to three-day intervals, usually commencing as early as two to three days following insertion of the expander. In 5 of the 12 patients, previously scarred skin was expanded to facilitate excision of areas of more dense scarring and scar contractures, more conventional methods having previously failed. Two of the expanders failed to achieve adequate expansion because of exposure of the device. One of the patients in whom the expander failed refused to have it reinserted. Complications included implant exposure (9 of 42), injection port exposure (1 of 42), infection (4 of 42), and a transient facial nerve palsy in 1 patient who was having her cheeks expanded. Except for one case, implant exposure did not preclude continued expansion and ultimate reconstruction.

Adult↗

Structural changes in the kidney of freshwater mud eel Amphipnous cuchia (Ham.) subjected to different osmotic conditions.

A histophysiological study was made of the kidney of Amphipnous cuchia subjected to different osmotic conditions (distilled water, 50% and 15% sodium chloride solution). These fish possess typical glomerular kidneys having nephrons composed of a glomerular body, neck segment, proximal convoluted segment (I & II), distal segment, and collecting duct system. When subjected to a hypotonic medium (distilled water) the fish show marked expansion in glomeruli resulting in 'glomerulitis'. A marked shrinkage in glomerular body tissue is found after 50% salt solution treatment and the fish die within one hour of immersion. Many pathological changes occur in the renal capsule and renal segment when the fish are treated with 15% salt solution. The glomerular bodies show shrinkage, degeneration and cyst formation. The glomerular shrinkage is probably due to constriction of arterioles which affects the filtration rate and thus protects against loss of water. Formation of cysts could be a protective device to save the glomeruli from degeneration. The renal tubules show hypertrophy, vacuolization, nuclear degeneration and cyst formation.

Anguilla↗

The image-combining computer microscope--an interactive instrument for morphometry of the nervous system.

The image-combining computer microscope is a new configuration of light microscope and computer graphics instrumentation which provides remarkable morphometric capabilities over a wide range of applications. The key component is the well known camera lucida, an image-combining device that is used to superimpose the computer graphics image upon the microscope's image of the object under study. Illumination need not be limited to the bright-field variety. The image superposition permits the investigator to study the object and acquire data from it while always looking through the microscope oculars. A computer controlled stepping motor driven stage is integrated with translations of the graphics image to permit image superposition and data acquisition at maximum visual magnification over the full expanse of a 25 X 25 mm tissue section. The investigator controls the system by means of a graphics tablet and a "Menu" area visible to him in the microscope's field of view. Spatial data in all 3 dimensions can be acquired easily since the z-axis is also stepping motor controlled. EM micrograph transparencies can be studied similarly. Stereological applications are possible by superimposing test grids upon the image. The system is self-contained and carries out data analysis programs written in C or Basic. Simplicity of operation has been emphasized throughout.

Animals↗

[Labial expansion].

Lip expansion is an old procedure used by some ethnic groups to follow traditions of their ancestry. Medically speaking since the beginning of the XIXth century, various devices have been designed for distending the angles of the mouth in order to recreate the normal width of the mouth aperture. In the recent years, thanks to the development and refinements of new flaps, expanding the lips is rarely necessary. In proper indications however, specially in the vermillon border, lip expansion remains a good indication.

Humans↗

In vivo tomographic assessment of the heart and blood vessels with intravascular ultrasound.

Intravascular ultrasound (IVUS) has emerged from being a research tool to becoming an intrinsic part of modern invasive cardiology mainly due to imaging micro anatomy in vivo. For the first time, it is possible to base therapeutic decisions not only on lumenograms but also on vessel wall assessment. IVUS has both diagnostic and intervention associated potential. The diagnostic strength of IVUS is its ability to describe compensatory coronary artery enlargement as a response to arteriosclerosis, to assess intermediate lesions, and to reveal occult left main stem disease and angiographically "silent" arteriosclerosis. The intervention associated potential of IVUS is the optimal device selection, i.e., rotablators in calcified lesions or atherectomy devices in large plaque burden. The effects of PTCA on vessel wall morphology can be studied in great detail and the effect on luminal gain can be assessed. Several groups have shown that the residual plaque area ("plaque burden") even after angiographically successful PTCA still lies in the range of 60%. A significant reduction in this number may influence long-term outcome after PTCA. Minimal luminal area and residual plaque area after PTCA seem to be indicators of restenosis, while the presence or absence of dissections seems to be less predictive. The main mechanism of restenosis after PTCA is vessel shrinkage, not intimal hyperplasia. Intravascular monitoring of stent expansion led to high-pressure stent deployment with a significant increase in post-procedural luminal diameters and the ability to withhold anticoagulation in patients with optimal stent deployment. In pulmonary and aortic diseases, IVUS contributed significantly to the understanding of aortic dissection and pulmonary hypertension. Additionally, with intracardiac ultrasound left and right ventricular function can be assessed. Intracardiac ultrasound has gained clinical usefulness for guiding transcatheter ablation in patients with conduction system abnormalities. In the future, integrated devices, such as balloons on IVUS catheters, steerable catheters, integrated flow and pressure transducers, tissue characterization, and 0.018" IVUS guide wire will further enhance the usefulness of IVUS.

Arteriosclerosis↗

Blood pumps: technologies and markets in transformation.

The heart failure industry or sector of blood pump technologies comprised of scientists, medicine, and business has inadequate attention from the financial community due to the perception of unmet market potential and regulatory hurdles. There are more than 20 mechanical circulatory support technologies currently in some stage of development. The application is defined initially for emerging technologies as bridge-to-transplant whereas more mature devices have focused on bridge-to-recovery and alternative-to-transplant. Regulatory hurdles and financing resources have dictated this initial application strategy. Whether a technology has valves, bearings, is magnetically suspended, acts as a pressure cuff, and so on, the future will belong in large part to those technologies that are less expensive, have improved ergonomics, are simpler in surgical application, and can demonstrate efficacy levels that are an improvement over today's approved devices. Today's devices have provided a valuable platform for the emerging technologies. However, there has been little market expansion over these past years, relative to the potential market. The cardiologist is the patient's gatekeeper, and drugs appear to be the therapy of choice as options are considered. Technologies without a business model will have a difficult time attracting much needed funding, the result being protracted development times or project termination. MicroMed has modified its ventricular assist device (VAD) focus, with a broader look at treating the heart failure patient. MicroMed recently entered into an agreement with Chrysalis Biotechnology, Inc., Galveston, TX, covering a synthetic peptide technology (Chrysalin) that when injected into tissue has demonstrated an angiogenic effect without the concerns inherent in recombinant angiogenic/growth factors. We believe a combination therapy of the DeBakey VAD-synthetic peptide could provide sufficient revascularization for bridge-to-recovery or as an alternative-to-transplant in certain patients.

Angiogenesis Inducing Agents↗

Lysine-based cluster mannosides that inhibit ligand binding to the human mannose receptor at nanomolar concentration.

In search of synthetic high affinity ligands for the mannose receptor, we synthesized a series of lysine-based oligomannosides containing two (M2L) to six (M6L5) terminal alpha-D-mannose groups that are connected with the backbone by flexible elongated spacers (16 A). The synthesized cluster mannosides were all able to displace binding of biotinylated ribonuclease B and tissue-type plasminogen activator to isolated human mannose receptor. The affinity of these cluster mannosides for the mannose receptor was continuously enhanced from 18-23 microM to 0.5-2.6 nM, with mannose valencies increasing from two to six. On average, expansion of the cluster mannoside with an additional alpha-D-mannose group resulted in a 10-fold increase in its affinity for the mannose receptor. M3L2 to M6L5 displayed negative cooperative inhibition of ligand binding to the mannose receptor, suggesting that binding of these mannosides involves multiple binding sites. The nanomolar affinity of the most potent ligand, the hexamannoside M6L5 makes it the most potent synthetic cluster mannoside for the mannose receptor yet developed. As a result of its high affinity and accessible synthesis, M6L5 not only is a powerful tool to study the mechanism of ligand binding by the mannose receptor, but it is also a promising targeting device to accomplish cell-specific delivery of genes and drugs to liver endothelial cells or macrophages in bone marrow, lungs, spleen, and atherosclerotic plaques.

Binding, Competitive↗

Directional power deposition from direct-coupled and catheter-cooled interstitial ultrasound applicators.

This research represents an experimental investigation of the directional power deposition capabilities of interstitial ultrasound applicators intended for applications in hyperthermia and thermal surgery for cancerous or benign disease. Direct-coupled and catheter-cooled ultrasound applicators were fabricated using cylindrical piezoceramic transducers sectored to produce 90 degrees, 180 degrees or 270 degrees active acoustic zones. The applicators were characterized through measurements of acoustic power output and intensity beam distributions in degassed water, in vitro temperature measurements in a perfused kidney model, and in vivo temperature distributions in pig thigh muscle. The angular power deposition patterns obtained in water were closely correlated to the resultant temperature distributions measured in the perfused kidney and in vivo pig thigh muscle. These sectored catheter-cooled and direct-coupled devices both demonstrated the ability to generate high temperatures (>50 degrees C) at sustained high power output levels (6-12 W) without degradation of the ultrasound transducers. Directional control of the energy deposition from the sectored ultrasound applicators was verified with corresponding temperature profiles in both the in vitro and in vivo experiments, as well as with angularly shaped thermal lesions. This is significant in that it demonstrates that heating in the angular expanse can be controlled with interstitial ultrasound applicators, thus providing more conformal thermal therapy by directing the thermal energy in the targeted tissue while protecting non-targeted tissue from thermal damage.

Animals↗

Vacuum-assisted closure: state of basic research and physiologic foundation.

A tremendous amount of research has been conducted in recent years investigating the mechanisms of action by which the application of subatmospheric pressure to wounds increases the rate of healing. Similarly, numerous studies have also been conducted examining the physiologic response of wounds to the applied subatmospheric pressure. However, many more need to be conducted. A series of basic studies examining the use of subatmospheric pressure to treat wounds is presented, including the original studies upon which the vacuum-assisted closure device was based (on blood flow, granulation tissue formation, bacterial clearance, and survival of random-pattern pedicle flaps). Subsequent studies analyzing removed fluids, envenomation/extravasation, burns, grafts, and in vitro tissue culture studies are also reviewed. Two broad mechanisms of action are proposed: removal of fluid and mechanical deformation. Fluid removal both decreases edema--thus decreasing interstitial pressure and shortening distances of diffusion--and removes soluble factors that may affect the healing process (both positively and negatively). The relationship of mechanical deformation to increased growth is well known to plastic surgeons, as it is the basis of tissue expansion. While much has been done, a great deal more needs to be done to elucidate the mechanisms of action responsible for the dramatic response seen clinically.

Animals↗

In vivo imaging of graft-versus-host-disease in mice.

We have developed a mouse system by which to track the migration and homing of cells in a setting of bone marrow transplantation (BMT)-induced graft-versus-host disease (GVHD) after systemic infusion using enhanced green fluorescence protein (eGFP) transgenic (Tg) cells and a simple application of a fluorescence stereomicroscope outfitted with a color charge-coupled device (CCD) camera. Whole body images of anesthetized mice taken at various time points after cell infusion revealed the early migration of allogeneic cells to peripheral lymphoid organs, with later infiltration of GVHD target organs. Localization of eGFP Tg cells could be seen through the skin of shaved mice, and internal organs were easily discernible. After allogeneic or syngeneic eGFP Tg cell infusion, representative mice were dissected to better visualize deeper internal organs and tissues. Infusion of different cell populations revealed distinct homing patterns, and this method also provided a simple way to identify the critical time points for expansion of the transplanted cells in various organs. This simple application of the fluorescence stereomicroscope will be valuable for GVHD and graft-versus-tumor studies in which visualization of cellular migration, expansion, and cell-cell interactions will be more informative when analyzed by such an intravital method.

Animals↗

Surface microarchitectural design in biomedical applications: in vivo analysis of tissue ingrowth in excimer laser-directed micropored scaffold for cardiovascular tissue engineering.

A micropatterned microporous segmented polyurethane film (20 x 12 mm in size, 30 micrometer thick) with four regions was prepared by excimer laser microprocessing to provide an in vivo model of transmural tissue ingrowth in an open cell-structured scaffold specially designed for cardiovascular tissue engineering. Three microporous regions had the same circular micropores (30 micrometer diameter) but different pore density arrangements (percentage of total pore area against unit area was 0.3%, 1.1%, and 4.5%), and the other region remained nonporous. The covered stent, prepared by wrapping the regionally different density-microporous film on an expandable metallic stent (approximately 3.1 mm in diameter), was delivered to the luminal surface of canine common carotid arteries and placed after expansion of the stent to a diameter of approximately 8 mm using a balloon catheter. At 4 weeks of implantation, all the covered stents (n = 10) were patent. The luminal surfaces of the covered stents were almost confluently endothelialized both in nonporous and microporous regions. Histological examination showed that the neointimal wall was formed by tissue ingrowth from host through micropores (transmural) and anastomotic sites. Thrombus formation occurred frequently in the lowest density porous region and nonporous region. With an increase in pore density, the thickness of the neointimal wall decreased. This study demonstrated how the micropore density of implanted devices influences tissue ingrowth in arterial implantation.

Angioplasty, Balloon↗

[Nuclear magnetic resonance (NMR) imaging of brain edema from sliced rat brain: preliminary report].

A series of the sliced rat brain were imaged by proton nuclear magnetic resonance (1H-NMR) using a Carr-Purcell-Meiboom-Gill sequence. The slices were obtained from the adult male Wistar rats, normal or suffering from vasogenic brain edema at 2, 6, 24Hr, 2Wk and 2Mo period after the application of cryo-injury. The imaging time was arranged 17 to 22 minutes dependently upon signal to noise ratio. The slice thickness was 1.2 mm, and pixel dimensions were 0.2 X 0.2 mm. Whereas a voxel size in our images is mere 1/1,200 compared to that reported about the prototype human NMR imaging devices, high resolution has been realized. The spatial resolution is very fine, as evidenced by the appearance of major internal structures of rat brain, and the object contrast is so high that cerebral white-gray contrast is excellent, although the difference in water concentration between them is only 7%. It has been impossible to measure serially in vivo change in water concentration of small organs as rat brain, NMR has the capability to generate images in response to tissue state of hydration, therefore we can easily recognize the extent and intensity of the brain edema, which has been defined as an expansion of the brain volume resulting from an increase in its fluid content. And in this study, using the prototype mini-NMR-CT of excellent spatial and contrast resolution, we have been able to show this advantage of NMR as a new tool for research in the field of neurological surgery.

Animals↗

[Elongation and coverage of an inguinal flap over a short forearm traumatic amputation stump].

A particularly short traumatic amputated forearm finally led to a simplified under-elbow prosthesis after a long surgical program including: 1) A progressive 8 cm ulnar lengthening with a Wagner device; 2) and a secondary groin flap resurfacing the distal stump. Complications essentially concerned the ulnar lengthening particularly because of a weak osseous callus. Final aesthetic and functional results are satisfying with a 6 years follow-up.

Adult↗

Development of a new extracorporeal whole-liver perfusion system.

We have developed a new extracorporeal whole-liver accommodation device in which a whole swine liver is placed in a physiological state by modeling the intraabdominal arrangement in the pig body, with the liver supported by a special inferior vena cava tube. Furthermore, we employed a diaphragm-type artificial heart in our system to produce pulsatile blood flow through the hepatic artery, which is considered to be indispensable to dilate peripheral vessels and supply oxygenated whole blood to the peripheral liver tissue. Beneficial effects were demonstrated in visual findings and bile juice secretion. The color of the liver surface in our system remained bright red, indicating that the liver vessels were well drained and free from congestion, and bile juice secretion was maintained at more than 10 ml/h throughout the perfusion period. Our system exhibited excellent ammonia removal and urea nitrogen synthesis, and serum aspartate aminotransferase levels showed no increase, indicating the absence of hepatocyte destruction. Histological findings showed that the liver could expand appropriately and was free from compression caused by its own weight. In conclusion, our original liver accommodation device enabled appropriate expansion of the whole liver and supplied adequate oxygenated blood to peripheral areas by means of a pulsatile pump.

Adsorption↗