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Biomedical subjects

T D Brown

Publications and source records attributed to T D Brown.

At least 217 records · Page 12Linked to original sources

Metallurgical analysis of five failed cast cobalt-chromium-molybdenum alloy hip prostheses.

The clinical and metallurigical characteristics of five cast cobalt-chromium-molybdenum alloy femoral hip prostheses which failed in vivo were evaluated. The devices included: two of the Howmedica Muller-Charnley design, two of the Howmedica Charnley design, and one of the Zimmer Aufranc-Turner design. Fractographic analyses demonstrated that the five devices had failed by fatigue which originated on the lateral aspect. Failure occurred after an average in vivo time of 80.4 months (approximately 6.7 years). Only two of the devices had Rockwell hardness values that were within the ASTM specifications for the alloy. Upon metallurgical examination, moderate to severe levels of gas porosity, interdendritic shrinkage, and nonmetallic inclusions were found in all of the devices. As expected, extremely large grain sizes also were observed in the devices examined. These results indicate that the metallurgical flaws and defects associated with the cast cobalt-chromium-molybdenum alloys used in these devices may preclude successful longterm performance and warrant manufacturer's attention.

Aged↗

Some characteristics of laminar flow velocity spectra detected by a 20 MHz pulsed ultrasound Doppler.

For the purpose of improving accuracy of noninvasive flow measurements in small (1-2 mm diameter) blood vessels, an existing 20 MHz pulsed ultrasound Doppler velocimeter (PUDVM) has been augmented to allow fast Fourier transformation (FFT) of its Doppler shift signal. The modified instrument was used to collect velocity spectra for a benchtop test section delivering precise Poiseuille flows at velocities in the range of physiological interest. The velocity spectra demonstrated a substantial degree of broadening, much of which was attributable to the geometry of the finite sample volume size. Several spectral indices were studied as a function of flow field variables. Results showed that the intensity-weighted mean Doppler shift frequency, when converted to its corresponding velocity vM, agreed very closely with the theoretically predicted local fluid velocity. Measurement linearity and repeatability were evaluated for a number of system variables, indicating that FFT performance was essentially unaffected by several parameters capable of causing major degradation of (phasic) Doppler shift signals produced by conventional zero-crossing-counter circuitry. As presently configured, the augmented PUDVM instrument is fully capable of detailed flow field mapping in small subcutaneous vessels such as human digital arteries.

Blood Flow Velocity↗

Sequencing of coronavirus IBV genomic RNA: three open reading frames in the 5' 'unique' region of mRNA D.

The nucleotide sequence of a genomic cDNA clone corresponding to the 5' terminal domain of mRNA D of the Beaudette strain of infectious bronchitis virus (IBV) has been determined. This region contains three open reading frames which predict polypeptides of molecular weights 6700 (6.7K), 7.4K and 12.4K. The predicted 12.4K polypeptide has a codon usage very similar to that predicted for the products of the IBV nucleocapsid, membrane and spike genes. The sequence also predicts a hydrophobic, potentially membrane-anchoring, region in the N terminal half of the 12.4K polypeptide, and a hydrophilic C terminus.

Amino Acid Sequence↗

Sequences of the nucleocapsid genes from two strains of avian infectious bronchitis virus.

cDNAs prepared from viral genomic RNA purified from two strains of infectious bronchitis virus (IBV) (Beaudette and M41) have been cloned into pBR322. Three of these clones, which contain the complete sequences of mRNA A for both strains, except for the leader sequences which are only present on the subgenomic messenger RNAs, have been sequenced using the dideoxy method. The sequences are similar for both strains, each containing a single long open reading frame of 1227 bases which predicts a polypeptide of molecular weight approximately 45 000. The genome position and size of this predicted polypeptide are consistent with it being the gene for the nucleocapsid protein. The amino acid sequence shows considerable homology with those of the nucleocapsids of murine hepatitis virus strains A59 and JHM. The major difference between the sequences determined for the two IBV strains is that the 3' non-coding region of the Beaudette strain contains a 184 base segment which is not present in the M41 strain.

Amino Acid Sequence↗

Cloning and sequencing of the gene encoding the spike protein of the coronavirus IBV.

RNA sequences encoding the surface projection (spike) of the coronavirus infectious bronchitis virus, strain Beaudette, have been cloned into pBR322 using cDNA primed with a specific oligonucleotide. A 5.3 kilobase viral insert in the clone pMB179 has been identified. The region of this clone coding for the spike gene has been sequenced by the chain termination method, and we present here the first report of DNA sequence data for a coronavirus spike protein, the protein which forms the characteristic 'corona' after which the group is named. The amino acid sequence of the primary translation product, deduced from the DNA sequence, predicts a polypeptide of 1162 amino acids with a molecular weight of 127 006. This has many interesting features which confirm and extend our knowledge of this recently characterized membrane glycoprotein. The polypeptide is subsequently cleaved to S1 and S2, and partial amino acid analysis of the amino-terminus of the S1 polypeptide has been employed to locate the position of this terminus of S1 within the large open reading frame. The amino acid analysis also reveals the presence of an 18 amino acid putative signal sequence on the primary translation product which is not present on the mature S1 polypeptide.

Amino Acid Sequence↗

A three-dimensional computational simulation of some sources of measurement artifact in microvascular pulsed ultrasound Doppler velocimetry.

Recent applications of 20 MHz pulsed ultrasound Doppler velocimetry (PUDVM) in microsurgical research have necessarily employed piezoelectric crystals whose diameter is not negligible compared to the lumen size (1-2 mm) of many vessels of interest. A three-dimensional numerical model was developed to explore relationships between actual and detected flow field parameters, for (steady) Poiseuille flow, when appreciable velocity gradients exist within the PUDVM sample volume. Validation studies showed that highly accurate velocity profiles could be obtained in the limiting case of a very small sample volume (0.1 mm radius), but that for currently employed crystals (approximately equal to 0.5 mm radius) there was appreciable underestimation of the centersteam velocity, and appreciable overestimation of the flow stream diameter. Errors in perceived velocity and flow rate were found to be relatively insensitive to perturbations in the sample volume thickness, in the size of the sampling range increment, or in the angle of insonation beam divergence. By contrast, these apparent flow parameters were found to be very sensitive to perturbations of sample volume diameter or of the Doppler angle. Small variations in the degree of partial sample volume overlap of the flowstream periphery were shown to be capable of causing large fluctuations in apparent flow stream diameter.

Blood Flow Velocity↗

The apparent elastic modulus of the juxtarticular subchondral bone of the femoral head.

An experiment was undertaken to obtain approximate values for the intrinsic elastic modulus of subchondral bone. Shallow spherical caps, with uniform and incrementally controlled thickness, were machined from subchondral bone in the weight-bearing regions of 11 fresh-frozen normal femoral head autopsy specimens. Under application of polar point loads, the measured deflections were compared with a corresponding analytical shell solution, thus allowing back-calculation of the apparent modulus. Analogous tests were performed on similarly shaped specimens of stock Plexiglas of known modulus in order to estimate the precision of the testing method. The aggregate results for subchondral bone showed that its intrinsic stiffness correlated inversely with nominal shell thickness, but even the thinnest (1.0 mm thick) of these shells had an apparent modulus (mean = 1.372 GN/m2, SD = 414 MN/m2) well below that generally accepted for "pure" cortical bone (about 14 GN/m2). This stiffness deficit was very likely due to the presence of histologically evident marrow spaces. However, the low apparent modulus values measured in this study may not be fully representative of complex in vivo behavior, because in the testing of excised shells there is no radial compressive stress transfer to underlying cancellous bone.

Cartilage, Articular↗

In vitro contact stress distribution on the femoral condyles.

Contact stress distributions were measured across the tibiofemoral joints of 11 fresh-frozen normal cadaver specimens. Local stress magnitudes were sensed by arrays of miniature piezoresistive transducers inset superficially in the cartilage of the femoral condyles. Knee joints were tested at 0, 10, 20, and 30 degrees of flexion and later retested at 0 degrees following medial and dual meniscectomies. For the intact joint, both the spatial mean and peak local contact stresses rose approximately linearly with the joint resultant, reaching levels of 2.6 and 8.0 MPa, respectively, at 3 kN of applied loading. Flexion angle variations in the range studied failed to cause significant changes in the major contact parameters. Although meniscectomies involved contact area reductions and consequent stress increases, such effects were more moderate than results previously seen for static loading of the tibial plateau.

Biomechanical Phenomena↗

A contact-coupled finite element analysis of the natural adult hip.

A non-linear two-dimensional finite element model was used to study phenomena of stress redistribution in the natural adult hip resulting from parametric material property variations in the juxtarticular regions of the femoral head. Despite the geometrical simplifications employed, the intra-articular contact stresses (computed using the FEAP program) were found to be in reasonable qualitative agreement with previous in vitro data for the case of a normal hip. Generalized sclerotic changes in the subchondral plate, as reflected either in apparent modulus increases or in plate thickening, were found to have only minor effects on the computed contact stress distribution, although stress levels within the plate itself were markedly influenced. Localized subchondral plate sclerosis, by contrast, led to marked stress elevations in the cartilage immediately overlying the stiffened bone. Cartilage modulus increases caused increased load uptake for a given imposed deformation, but involved stress distribution increases which were very nearly linearly proportional to the increases in resultant load magnitude. Friction coefficient elevations had no noticeable effects on normal contact stress or upon overall load transmission, but involved complex, possibly slip-related, changes in intra-articular and cartilaginous shear stresses.

Cartilage, Articular↗

Finite element studies of some juxtarticular stress changes due to localized subchondral stiffening.

A finite element analysis was undertaken in concert with an animal model of mechanically-induced osteoarthritis. The numerical model was used to explore stress transmission anomalies associated with localized subchondral stiffening due to implantation of small cylindrical plugs immediately below the subchondral plate of sheep. The quasi-static, plane strain computational formulation included solution of the non-linear intra-articular contact problem, and was validated by comparison with a corresponding analytical solution and with the in vivo experimental results. The numerical results showed that stress aberrations due to metal implant insertion were felt most greatly in the bone immediately surrounding the implant, but that nominal compressive stress elevations up to about 50% could also be induced in the overlying deep hyaline cartilage layer. This localized cartilage stress elevation following the insertion of a metal plug could be seriously affected by a number of factors, including the positioning of the implant, variation in the area of intra-articular contact, or the elastic modulus of the cancellous bone and/or subchondral plate. Experimentally-observed fibrous encapsulation also reduced the cartilage stress elevation effect, but later bony remodelling and the development of a corticalized shell around the implant encapsulation served to re-elevate the local cartilage stresses.

Animals↗

Sequence of the membrane protein gene from avian coronavirus IBV.

cDNA clones prepared from genomic RNA of coronavirus IBV have been sequenced. The nucleotide sequence for the complete 5' region of mRNA C, which is not present in mRNAs A and B, has been determined. A sequence of 1224 bases is presented which contains a long open reading frame predicting a polypeptide of molecular weight 25 443. This is in agreement with the molecular weight of 23 000 reported for the unglycosylated form of the membrane polypeptide.

Base Sequence↗

Monoclonal antibodies to the S1 spike and membrane proteins of avian infectious bronchitis coronavirus strain Massachusetts M41.

We have established four murine hybridoma cell lines which secrete specific antibody to avian infectious bronchitis virus (IBV) strain Massachusetts M41. Two monoclonal antibodies reacted with the spike protein and two reacted with the membrane protein. The specificity of the monoclonal antibodies for the external structural proteins was detected by immunoprecipitations using radiolabelled virus. The reactions of the monoclonal antibodies showed that one (S1) of the two glycopolypeptides associated with the spike protein has a strain-specific region involved in neutralization and haemagglutination, and the membrane protein has antigenic determinants which are present on the three strains of IBV tested (M41, Beaudette and D41).

Antibodies, Monoclonal↗

A leader sequence is present on mRNA A of avian infectious bronchitis virus.

The subgenomic mRNAs of the fowl coronavirus infectious bronchitis virus (IBV) form a 3' co-terminal or 'nested' set. The RNase T1 oligonucleotide mapping data which demonstrated this form of sequence organization provided no evidence for the presence of non-contiguous (leader) sequences fused to the 5' termini of the mRNAs. However, we have been able to demonstrate, by extension of an end-labelled synthetic oligonucleotide primer, the presence of a leader sequence on IBV mRNA A. Sequencing by the chemical degradation method of the extended product has yielded the almost complete sequence of the 60 base leader and its point of fusion to the sequence of the virus genomic RNA.

Base Sequence↗

Stability of acetabular fractures after internal fixation. A cadaveric study.

The rigidity of a transverse acetabular fracture in a laboratory cadaveric model immobilized by internal fixation was studied. On the application of a longitudinal load imposed on the fifth lumbar vertebra, four modes of displacement of the acetabular fracture were monitored by the use of variable impedance transducers. The rigidity of various combinations of lag screws and plates was assessed. The fracture deformations documented were generally quite small at any observation point with any of the fixation methods, and in most cases they were recoverable on load release. Anterior column lag screw fixation combined with plate fixation of the posterior column provided a degree of stability indistinguishable from that of other methods, and allowed the minimal exposure and devascularization of the pelvis. The 3.5 mm reconstruction plate, which is readily contoured to the intricate peri-acetabular bony structure, showed no significant difference in rigidity compared to the other apparently more rigid plates under study.

Acetabulum↗

In vitro contact stress distributions in the natural human hip.

Time variant distributions of intra-articular contact stress were assembled from direct measurement in seventeen grossly normal fresh cadaveric hips. Local stresses were sensed by arrays of 24 compliant miniature transducers inset superficially in the femoral head cartilage. Local contact stress magnitude was usually found to rise nearly linearly with applied joint loads in excess of about 1000 N. The sites of maximum local stress were found to underlie the general region of the acetabular dome. For a resultant joint load of 2700 N, the spatial mean contact stress and peak local contact stress averaged 2.92 MN m-2 and 8.80 MN m-2, respectively, for the 68 loading cycles analyzed. The full contact stress patterns were irregular and complex, but most commonly the general feature was a central band or 'ridge' of pressure elevation, oriented in an approximately anterior-to-posterior direction.

Biomechanical Phenomena↗