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Biomedical subjects

E H Frank

Publications and source records attributed to E H Frank.

At least 19 recordsLinked to original sources

Assessing automobile head restraint positioning in Portland, Oregon.

OBJECTIVE: Automobile head restraints, when used properly, have been shown to decrease the incidence and severity of whiplash injuries to the neck. Before the development of a public campaign on proper head restraint positioning, the authors assessed head restraint positioning and public understanding. DESIGN: Over a one month period, the position of the vehicle head restraint of drivers was observed in moving cars in the city of Portland, Oregon (population 530,000). Optimal position was defined as having the head restraint above the ears with the back of the head touching the head restraint. A questionnaire on head restraint understanding was administered to people during jury service. RESULTS: Of the 4287 drivers observed, 1% (n = 30) had no head restraint on their seat, 4% (n = 158) had a fixed head restraint, and 95% (n = 4099) had an adjustable head restraint. Among the fixed head restraints, 21% (33/158) were positioned optimally with no horizontal gap. Among the adjustable head restraints, only 7% (280/4099) had optimal head restraint positioning. Overall, 93% (3974/4287) of all head restraints observed were suboptimally positioned. Seventy five percent (38/51) of polled Portland residents identified safety as the primary head restraint function. CONCLUSION: Ninety three percent of all head restraints observed were suboptimally positioned. Fixed head restraints were three times more likely to be in optimal position than adjustable head restraints (21% v 7%). Most polled Portland residents understood the proper function and positioning of head restraints. This discrepancy between actual practice and understanding should be addressed with public education and manufacturer design changes.

Automobiles↗

An endoscopic dural retractor for spinal stenosis surgery.

Adequate neural decompression is the goal of lumbar stenosis surgery. Often because of limited visualization of the nerve root, significant portions of the facet joints are removed for decompression enhancing the potential for the development of instability. Clearly, the goal to better visualize the anatomy of the lateral recess while decompressing the nerve root may result in better root decompression and a smaller potential for instability secondary to bone loss. In order to accomplish this goal we have designed an endoscopic dural retractor that while retracting the dura permits simultaneous visualization of the anatomy of the lateral recess and the activity of instruments used to decompress it. The endoscopic dural retractor contains a 10000 pixel endoscope that allows a direct lateral view into the lateral recess while the dura is being retracted. This is a view that cannot be achieved with the operating microscope. One can easily appreciate the anatomy of the lateral recess including the facet joint, ligamentum flavum, lateral dura and nerve root. Ten geriatric cadaver lateral recesses were decompressed endoscopically using the endoscopic retractor. Compression of the nerve root by the facet and ligamentum could easily be identified. One could visually monitor the use of instruments on removal of ligamentum flava and bone compressing the nerve root. In all cases the ligament was easily removed and the facet joint was undercut only enough to decompress the nerve. This instrument has the potential for less invasive decompression of spinal stenosis and further study of its utility is planned.

Decompression, Surgical↗

An endoscopic curved Kerrison rongeur for spinal stenosis surgery.

OBJECTIVE: Adequate neural decompression with minimal structural alteration is the goal of lumbar stenosis surgery. Often because of limited visualization significant parts of the facet joints are removed enhancing the potential for developing instability. To overcome this problem we have developed a small curved Kerrison rongeur that contains a 10 000-pixel endoscope. This instrument allows one to visualize and decompress structures within the lateral recess that may have required more extensive removal of portions of the facet joints. METHODS: Ten patients with symptomatic lumbar spinal stenosis were decompressed using the endoscopic rongeur. RESULTS: Compression of the lateral dura and nerve root by the facet and ligamentum could easily be identified. In all cases the ligament could be easily removed and the facet joint was undercut only enough to decompress the nerve. CONCLUSION: This instrument has the potential for less invasive decompression of spinal stenosis and further study of its utility is planned.

Endoscopes↗

Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants.

Chondrocytes are known to sense and respond to mechanical and physicochemical stimuli by multiple regulatory pathways, including upstream signaling, transcription, translation, posttranslational modifications, and vesicular transport. Due to the complexity of identifying the biophysical phenomena that occur during cartilage loading in vivo, the regulatory mechanisms that govern chondrocyte mechanotransduction are not fully understood. Recent studies have shown that fluid flow during dynamic compression of cartilage explants can stimulate proteoglycan and protein synthesis. In this study, we examined the effect of deformations of cell and extracellular matrix on chondrocyte biosynthesis. We used tissue shear loading, since tissue shear causes little volumetric deformation and can thereby decouple fluid flow from cell and matrix deformation. Shear loading was applied over a wide range of frequencies, 0.01-1.0 Hz, using 1-3% sinusoidal shear strain amplitudes, and the resulting proteoglycan and protein syntheses were measured using radiolabel incorporation. In addition, quantitative autoradiography was used to investigate spatial variations in matrix biosynthesis and to correlate these variations with the spatial profiles of biophysical stimuli. Our data show that tissue shear loading at 1-3% strain amplitude stimulated the synthesis of protein by approximately 50% and proteoglycans by approximately 25% at frequencies between 0.01 and 1.0 Hz. The relatively uniform patterns of biosynthesis in the radial and vertical directions within cylindrical explants revealed by autoradiography suggest that the stimulatory effect was associated with the relatively uniform deformation caused by simple shear loading. These results suggest that chondrocytes can respond to tissue shear stress-initiated pathways for the production of collagen and proteoglycan, which include deformation of cells and pericellular matrix, even in the absence of macroscopic tissue-level fluid flow.

Analysis of Variance↗

The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I.

Articular cartilage is routinely subjected to mechanical forces and to cell-regulatory molecules. Previous studies have shown that mechanical stimuli can influence articular chondrocyte metabolic activity, and biochemical studies have shown that growth factors and cytokines control many of the same cell functions. Little is known, however, of the relationships or interplay, if any, between these two key components of the articular environment. This study investigated the comparative and interactive effects of low amplitude, sinusoidal, dynamic compression and insulin-like growth factor-I (IGF-I), a polypeptide in synovial fluid that is anabolic for cartilage. In bovine patellofemoral cartilage explants, IGF-I increased protein and proteoglycan synthesis 90% and 120%, respectively while dynamic compression increased protein and proteoglycan synthesis 40% and 90%, respectively. Stimulation by IGF-I was significantly greater than by dynamic compression for both protein and proteoglycan synthesis. When applied together, the two stimuli enhanced protein and proteoglycan synthesis by 180% and 290%, respectively, a degree greater than that achieved by either stimulus alone. IGF-I augmented protein synthesis with a time constant of 12.2 h. Dynamic compression increased protein synthesis with a time constant of 2.9 h, a rate significantly faster than that of IGF-I, suggesting that these signals act via distinct cell activation pathways. When used together, dynamic compression and IGF-I acted with a time constant of 5.6 h. Thus, dynamic compression accelerated the biosynthetic response to IGF-I and increased transport of IGF-I into the articular cartilage matrix, suggesting that, in addition to independently stimulating articular chondrocytes, cyclic compression may improve the access of soluble growth factors to these relatively isolated cells.

Animals↗

Injurious mechanical compression of bovine articular cartilage induces chondrocyte apoptosis.

A bovine cartilage explant system was used to evaluate the effects of injurious compression on chondrocyte apoptosis and matrix biochemical and biomechanical properties within intact cartilage. Disks of newborn bovine articular cartilage were compressed in vitro to various peak stress levels and chondrocyte apoptotic cell death, tissue biomechanical properties, tissue swelling, glycosaminoglycan loss, and nitrite levels were quantified. Chondrocyte apoptosis occurred at peak stresses as low as 4.5 MPa and increased with peak stress in a dose-dependent manner. This increase in apoptosis was maximal by 24 h after the termination of the loading protocol. At high peak stresses (>20 MPa), greater than 50% of cells apoptosed. When measured in uniaxial confined compression, the equilibrium and dynamic stiffness of explants decreased with the severity of injurious load, although this trend was not significant until 24-MPa peak stress. In contrast, the equilibrium and dynamic stiffness measured in radially unconfined compression decreased significantly after injurious stresses of 12 and 7 MPa, respectively. Together, these results suggested that injurious compression caused a degradation of the collagen fibril network in the 7- to 12-MPa range. Consistent with this hypothesis, injurious compression caused a dose-dependent increase in tissue swelling, significant by 13-MPa peak stress. Glycosaminoglycans were also released from the cartilage in a dose-dependent manner, significant by 6- to 13-MPa peak stress. Nitrite levels were significantly increased above controls at 20-MPa peak stress. Together, these data suggest that injurious compression can stimulate cell death as well as a range of biomechanical and biochemical alterations to the matrix and, possibly, chondrocyte nitric oxide expression. Interestingly, chondrocyte programmed cell death appears to take place at stresses lower than those required to stimulate cartilage matrix degradation and biomechanical changes. While chondrocyte apoptosis may therefore be one of the earliest responses to tissue injury, it is currently unclear whether this initial cellular response subsequently drives cartilage matrix degradation and changes in the biomechanical properties of the tissue.

Animals↗

The insulin-like growth factors (IGFs) I and II bind to articular cartilage via the IGF-binding proteins.

Bovine articular cartilage discs (3 mm diameter x 400 micrometer thick) were equilibrated in buffer containing (125)I-insulin-like growth factor (IGF)-I (4 degrees C) +/- unlabeled IGF-I or IGF-II. Competition for binding to cartilage discs by each unlabeled IGF was concentration-dependent, with ED(50) values for inhibition of (125)I-IGF-I binding of 11 and 10 nM for IGF-I and -II, respectively, and saturation by 50 nM. By contrast, an analog of IGF-I with very low affinity for the insulin-like growth factor-binding proteins (IGF-BPs), des-(1-3)-IGF-I, was not competitive with (125)I-IGF-I for cartilage binding even at 100-400 nM. Binding of the (125)I-labeled IGF-II isoform to cartilage was competed for by unlabeled IGF-I or -II, with ED(50)s of 160 and 8 nM, respectively. This probably reflected the differential affinities of the endogenous IGF-BPs (IGF-BP-6 and -2) for IGF-II/IGF-I. Transport of (125)I-IGF-I was also measured in an apparatus that allows diffusion only across the discs (400 micrometer), by addition to one side and continuous monitoring of efflux on the other side. The time lag for transport of (125)I-IGF was 266 min, an order of magnitude longer than the theoretical prediction for free diffusion in the matrix. (125)I-IGF-I transport then reached a steady state rate (% efflux of total added (125)I-IGF/unit time), which was subsequently accelerated approximately 2-fold by addition of an excess of unlabeled IGF-I. Taken together, these results indicate that IGF binding to cartilage, mostly through the IGF-BPs, regulates the transport of IGFs in articular cartilage, probably contributing to the control of their paracrine activities.

Animals↗

A versatile shear and compression apparatus for mechanical stimulation of tissue culture explants.

We have developed an incubator housed, biaxial-tissue-loading device capable of applying axial deformations as small as 1 microm and sinusoidal rotations as small as 0.01 degrees. Axial resolution is 50 nm for applying sinewaves as low as 10 microm (or 1% based on a 1 mm thickness) or as large as 100 microm. Rotational resolution is 0.0005 degrees. The machine is small enough (30 cm high x 25 cm x 20 cm) to be placed in a standard incubator for long-term tissue culture loading studies. In metabolic studies described here, application of sinusoidal macroscopic shear deformation to articular cartilage explants resulted in a significant increase in the synthesis of proteoglycan and proteins (uptake of (35)S-sulfate and (3)H-proline) over controls held at the same static offset compression.

Animals↗

Cartilage tissue remodeling in response to mechanical forces.

Recent studies suggest that there are multiple regulatory pathways by which chondrocytes in articular cartilage sense and respond to mechanical stimuli, including upstream signaling pathways and mechanisms that may lead to direct changes at the level of transcription, translation, post-translational modifications, and cell-mediated extracellular assembly and degradation of the tissue matrix. This review focuses on the effects of mechanical loading on cartilage and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair of this tissue. The effects of compression and tissue shear deformation are compared, and approaches to the study of mechanical regulation of gene expression are described. Of particular interest regarding dense connective tissues, recent experiments have shown that mechanotransduction is critically important in vivo in the cell-mediated feedback between physical stimuli, the molecular structure of newly synthesized matrix molecules, and the resulting macroscopic biomechanical properties of the tissue.

Animals↗

An endoscopic aneurysm clip applicator: preliminary development.

Visualization of an aneurysm and its associated vessels is necessary for the proper application of aneurysm clips. Microscopes provide binocular magnification and excellent illumination but often visualization is obscured by overriding vessels and the limitation of the operative approach. If this occurs the aneurysm may be incompletely clipped or small perforators may be included in the clip. In an attempt to improve visualization during aneurysm clipping we have incorporated a small endoscope into the aneurysm clip applicator so that the tips of the clip can be observed at all times. Here we report our initial experimental results with this instrument.

Cadaver↗

A novel endoscopic approach to anterior odontoid screw fixation: technical note.

Techniques for operative management for type II odontoid fractures have continuously been refined with anterior odontoid screw arthrodesis having a clear advantage in maintaining normal motion. We have refined the technique of odontoid screw fixation further with the introduction of an endoscopic approach developed by the senior author. The necks of two partially embalmed cadavers were slightly extended under fluoroscopic guidance to simulate a reduced, anteriorly displaced type II fracture. Using a guide wire, graduated plastic sheath and endoscopic guidance, a solid 45 mm bone screw was passed through the odontoid with the aid of biplanar fluoroscopy. There were no apparent complications and no damage to surrounding vital structures. Anterior screw fixation of the odontoid is an established technique that provides adequate fixation, but the procedure can be technically demanding secondary to awkward tissue retraction. We present a percutaneous technique that obviates the need for tissue retraction while achieving an excellent result with only a modicum of effort.

Arthroscopy↗

Subdural empyema complicating cerebrospinal fluid shunt infection.

Subdural empyema has not been reported previously as a complication of cerebrospinal fluid (CSF) shunt surgery. An infant submitted to CSF shunt insertion for congenital hydrocephalus developed subdural empyema after a failed attempt to treat a superficial scalp wound infection with oral antibiotics. Enterobacter cloacae was isolated from the empyema. Temporizing management of the preceding superficial wound infection with oral antibiotics probably was the cause of this exotic pathogen. The treatment of infected scalp wounds contiguous with shunt hardware must be surgical.

Empyema, Subdural↗

The use of small malleable endoscopes to assess pedicle screw placement: technical note.

Because the improper insertion of pedicle screws can be associated with significant neurologic morbidity, attempts are being made to improve on the accuracy of pedicle screw placement. As a possible strategy we have studied the use of small malleable endoscopes to explore the pedicle and exiting nerve root during and after pedicle screw placement. These small endoscopes are 1.2 mm in diameter and can be bent so that the superior, medial and inferior walls of the pedicle can be visualized. Additionally, the nerve roots superior to and inferior to the pedicle can be seen throughout their entire intraspinal course. Using these endoscopes in ten patients requiring the placement of forty-four pedicle screws we were able to visualize the pedicles and nerve roots in all cases. The endoscope demonstrated that one screw had penetrated the inferior cortex of the pedicle. This penetration was not palpable with blind probing of the pedicle and foramina. These cases suggest that this simple technique may be of use in limiting improper pedicle screw placement.

Bone Screws↗

A malleable endoscopic suction instrument: technical note.

Flexible endoscopes are being employed for a variety of neurosurgical procedures. These instruments have drawbacks, especially in their ability to evacuate clotted blood. We have attempted to rethink the design of these instruments and have developed a malleable endoscopic suction instrument. This has proved to be helpful in a variety of intracranial and intraspinal procedures.

Endoscopes↗

Inhibition of cartilage degradation and changes in physical properties induced by IL-1beta and retinoic acid using matrix metalloproteinase inhibitors.

Bovine cartilage explants were treated with 100 ng/ml recombinant human interleukin-1beta (IL-1beta) or 1 microM all-trans retinoic acid (RA) and changes in biochemical, biomechanical, and physicochemical properties were assessed. Additionally, samples cultured with IL-1beta or RA were treated with 4 microM recombinant human tissue inhibitor of metalloproteinases-1 (TIMP-1) or a synthetic metalloproteinase inhibitor (L-758,354) to inhibit this degradation. Treatment with IL-1beta or RA each resulted in >90% GAG loss after 8 days in culture. Addition of TIMP or L-758,354 to the culture media inhibited IL-1beta-induced loss of tissue GAG by 40 and 65%, respectively, and inhibited RA-induced GAG loss by 35 and 65%, respectively. Analysis of degradation products in the culture media using a G1 antibody indicated that IL-1beta- and RA-treated plugs released 68-kDa fragments of aggrecan, corresponding to a segment of the aggrecan core protein from the G1 domain to the C-terminus NITEGE, consistent with "aggrecanase" activity. Release of the G1 fragment was inhibited by treatment with L-758,354. Both IL-1beta and RA induced significant loss of hyaluronan from cartilage explants after 8 days of exposure and HA loss was also inhibited by addition of L-756,354 to the culture media. IL-1beta, but not RA, induced a significant increase in swelling ratio (wet weight in 0.01 M NaCl normalized to wet weight in DMEM) after 8 days in culture, consistent with degradation of the collagen network, and the increase in tissue swelling was inhibited by treatment with TIMP-1 or L-758,354. Exposure to IL-1beta or RA resulted in significant changes in cartilage physical properties including streaming potential, equilibrium modulus, hydraulic permeability, and electrokinetic coupling coefficient after 8 days in culture, and these changes were inhibited by 40-90% by exposure to TIMP and by 50-90% by exposure to L-758,354. Measurement of dynamic streaming potential showed that changes due to treatment with IL-1beta alone were highly dependent in compression frequency, with dramatic changes seen at high frequency prior to changes in mechanical properties, and little initial change seen at low frequency. Streaming potential and equilibrium modulus of explants treated with RA decreased to 10% of their initial values after 8 days in culture, but decreased to only 40 and 90%, respectively, when treated with RA plus TIMP-1.

Aggrecans↗

An endoscopic pedicle probe: preliminary development.

Insertion of pedicle screws in the thoracolumbar spine can be challenging. Incorrect placement can lead to a failure of fusion or to significant neurologic morbidity. Recently, techniques utilizing intraoperative monitoring and stereotaxis have been developed to achieve proper screw placement. While these techniques may be accurate, they are expensive and may require additional operating room personnel. We have developed an endoscopic pedicle probe for placement of pedicle screws that may overcome some of these limitations. A small 1.2 mm endoscope was adapted to fit within a hollow pedicle probe. Irrigation was provided via a separate channel within the endoscope. Images from the probe were displayed both on a monitor screen and on a heads up display. The endoscopic probe was used to probe 36 sawbone and 22 cadaver thoracolumbar pedicles. After cannulation each specimen was examined to assess nonvisualized pedicle perforation. In sawbones, perforation was visualized endoscopically in 3 pedicles (8%) with no further perforations found on later direct examination. In cadavers the cortical cancellous interface was adequately visualized and no perforations occurred. These preliminary results suggest that the endoscopic probe may have utility in the placement of thoracolumbar pedicle screws.

Bone Screws↗

Contributions of fluid convection and electrical migration to transport in cartilage: relevance to loading.

We have studied the contributions of diffusion, fluid flow and electrical migration to molecular transport through adult articular cartilage explants using neutral and charged solutes that were either radiolabeled (3H2O, [35S]sulfate, [3H]thymidine, [3H]raffinose, and a synthetic matrix metalloproteinase inhibitor) or fluorescently tagged (NSPA and Lissamine-dextran). In order to induce fluid flow within the cartilage matrix without mechanical deformation, electric current densities were applied across cartilage disks. These currents produced electroosmotic fluid velocities of 1-2 microns/s, magnitudes that have been reported to exist during joint loading in vivo. This fluid convection enhanced neutral solute flux relative to passive diffusion alone by a factor that increased with the size of the solute. While the enhancement factor for 3H2O was 2.3-fold, that for [3H]raffinose (594 Da) and similar sized neutral solutes was 10-fold, suggesting that the effect of fluid flow is important even for small solutes. The largest enhancement (25-fold) was seen for the neutral 10-kDa Lissamine-dextran, confirming that fluid convection is most important for large solutes. We also studied the electrophoretic contribution to solute flux, which is relevant to the presence of intratissue streaming potentials induced during loading in vivo. Using the negatively charged [35S]sulfate ion with a range of current densities, as much as a 10-fold enhancement in flux was observed. Values for the intrinsic transport properties of the solutes (e.g., diffusivity, electrical mobility, hydrodynamic hindrance factor) can be obtained from the data.

Animals↗