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Biomedical subjects

R M Hall

Publications and source records attributed to R M Hall.

At least 19 recordsLinked to original sources

Measurement of canal occlusion during the thoracolumbar burst fracture process.

Post-injury CT scans are often used following burst fracture trauma as an indication for decompressive surgery. Literature suggests, however, that there is little correlation between the observed fragment position and the level of neurological injury or recovery. Several studies have aimed to establish the processes that occur during the fracture using indirect methods such as pressure measurements and pre/post impact CT scans. The purpose of this study was to develop a direct method of measuring spinal canal occlusion during a simulated burst fracture by using a high-speed video technique. The fractures were produced by dropping a mass from a measured height onto three-vertebra bovine specimens in a custom-built rig. The specimens were constrained to deform only in the impact direction such that pure compression fractures were generated. The spinal cord was removed prior to testing and the video system set up to film the inside of the spinal canal during the impact. A second camera was used to film the outside of the specimen to observe possible buckling during impact. The video images were analysed to determine how the cross-sectional area of the spinal canal changed during the event. The images clearly showed a fragment of bone being projected from the vertebral body into the spinal canal and recoiling to the final resting position. To validate the results, CT scans were taken pre- and post-impact and the percentage canal occlusion was calculated. There was good agreement between the final canal occlusion measured from the video images and the CT scans.

Animals↗

Indications of disordered eating behaviour in adolescent patients with idiopathic scoliosis.

We have investigated whether patients with adolescent-onset idiopathic scoliosis (AIS) are more likely to have a low body-weight. Measurements of weight, height and body mass index (BMI) were made in 44 young women with AIS and compared with age- and gender-adjusted normative data. The body mass criteria of the International Classification of Diseases for eating disorders was used to determine how many patients were within the range considered to be 'eating disordered'. Compared with the normative data, the AIS group did not differ significantly in terms of height, (p = 0.646), but they were significantly lighter (p < 0.001) and had significantly lower BMI scores (p < 0.001); 25% of the series had BMI scores which were within the range considered to be anorexic. The relationship between a diagnosis of AIS and low body-weight may indicate disordered eating and is thus a cause for concern, particularly in the light of the well-established relationship between eating psychopathology and osteoporosis. Aspects of organic health may need to be considered in addition to the cosmetic deformity.

Adolescent↗

Family of class 1 integrons related to In4 from Tn1696.

The class 1 integron In28, found in the multidrug resistance transposon Tn1403, was found to be located in the res site of the backbone transposon and is flanked by a 5-bp direct duplication, indicating that it reached this position by transposition. In28 has a backbone structure related to that of In4, but has lost internal sequences, including the sul1 gene, due to an IS6100-mediated deletion. In28 also lacks the partial copy of IS6100 found in In4 and contains different gene cassettes, blaP1, cmlA1, and aadA1. In1, the class 1 integron found in the multidrug resistance plasmid R46, is also located in a putative res site and belongs to the In4 group. In1 has a shorter internal deletion than In28 and has also lost one end. Additional integrons with structures related to In4 were also found in databases, and most of them had also lost either one end or internal regions or both. Tn610 belongs to this group.

Base Sequence↗

Transposons Tn1696 and Tn21 and their integrons In4 and In2 have independent origins.

The first 13.6 kb of the mercury and multidrug resistance transposon Tn1696, which includes the class 1 integron In4, has been sequenced. In4 is 8.33 kb long and contains the 5'-conserved segment (5'-CS) and 2.24 kb of the 3'-conserved segment (3'-CS) flanking four integrated cassettes. The 3'-CS region is followed by one full copy and an adjacent partial copy of the insertion sequence IS6100 flanked, in inverse orientation, by two short segments (123 and 152 bp) from the outer right-hand end of class 1 integrons. This structure is representative of a distinct group of class 1 integrons that differs from In2, found in Tn21, and other related class 1 integrons. In4 does not include transposition genes but is bounded by characteristic 25-bp inverted repeats and flanked by a direct duplication of 5 bp of the target sequence, indicating that it was inserted by a transpositional mechanism. In4 lies between the resII and resI sites of a backbone mercury resistance transposon which is >99.5% identical to Tn5036. Although Tn21 and Tn1696 are both classified as members of the Tn21 subfamily of the Tn3 transposon family, the backbone mercury resistance transposons are only 79 to 96% identical. Tn21 also contains a region of about 0.7 kb not found in Tn1696. The integrons In2 and In4 carrying the antibiotic resistance genes have been inserted at different locations into distinct ancestral mercury resistance transposons. Thus, Tn21 and Tn1696 have independent histories and origins. Other transposons (Tn1403 and Tn1412) that include a class 1 integron also have independent origins. In all except Tn21, the integron is located within the res region of the backbone transposon.

Anti-Infective Agents, Local↗

Efficiency of recombination reactions catalyzed by class 1 integron integrase IntI1.

The class 1 integron integrase, IntI1, recognizes two distinct types of recombination sites, attI sites, found in integrons, and members of the 59-be family, found in gene cassettes. The efficiencies of the integrative version of the three possible reactions, i.e., between two 59-be, between attI1 and a 59-be, or between two attI1 sites, were compared. Recombination events involving two attI1 sites were significantly less efficient than the reactions in which a 59-be participated, and the attI1 x 59-be reaction was generally preferred over the 59-be x 59-be reaction. Recombination of attI1 with secondary sites was less efficient than the 59-be x secondary site reaction.

Attachment Sites, Microbiological↗

The effect of socket design, materials and liner thickness on the wear of the porous coated anatomic total hip replacement.

The wear of joint replacement prostheses represents the greatest challenge to their continued development. Parameters such as polyethylene quality, liner thickness and metal backing have all been implicated as potential detractors in the search for the lowest-wearing socket. This study examined the effect of these parameters through an extensive study of the two versions of the porous coated anatomic (PCA) hip prosthesis (one-piece socket and snaplock socket). For the whole cohort the wear rate was found to be 88 (SE 10) mm3/year and the clinical wear factor was 2.00 (SE 0.28) x 10(-6) mm3/N m. When the two socket types were investigated individually, the wear factors found were 2.39 (SE 0.44) x 10(-6)mm3/N m and 0.99 (SE 0.25) x 10(-6) mm3/N m for the one-piece and snaplock, respectively. This illustrates that the metal backing per se does not predispose these sockets to rapid wear. The good wear performance of the snaplock liner may be attributed to the high quality of the ultra-high molecular weight polyethylene (UHMWPE) used and the shorter implantation period compared to that for the one-piece design. No correlation was found between the thickness of the liner and the clinical wear factor. Within the range of thicknesses tested here, UHMWPE thickness is not an influential parameter for the hip prosthesis and this is confirmed

Arthroplasty, Replacement, Hip↗

The production of novel sordarin analogues by biotransformation.

The biotransformation of the fungal protein synthesis inhibitor sordarin is reported. Nine taxonomically diverse organisms supported the isolation and identification of twelve modified products. The structural diversity of the biotransformation products observed and their value in supporting further chemistry is discussed.

Antifungal Agents↗

Characterisation of a chloramphenicol acetyltransferase determinant found in the chromosome of Pseudomonas aeruginosa.

The open reading frame (ORF) in the Pseudomonas aeruginosa chromosome, whose product resembles the chloramphenicol acetyltransferases (CAT) belonging to the CATB family, was cloned and shown to confer resistance to chloramphenicol (Cm) in Escherichia coli. The determinant was therefore named catB7 and the corresponding protein CATB7. When the copy number and expression signals were identical, the catB7 gene conferred resistance to Cm at a level slightly lower than those of three other catB genes. CATB7 resembles other CATBs in that it acetylates Cm but not 1-acetoxy-Cm. For CATB7, the K(m) values for acetyl-CoA and Cm were 5.0-5.4-fold higher than the corresponding values for each of the three other CATB proteins (CATB1, CATB3 and CATB5) examined and the Vmax was 5-6 fold lower. Using PCR, the catB7 gene was found in all six P. aeruginosa strains examined but not in any other species of pseudomonad tested. Weak CAT activity was detected in crude cell extracts from five of the six P. aeruginosa strains. However, this activity did not correlate with the Cm susceptibility of the strains, indicating that catB7 is not likely to be the major determinant of intrinsic Cm resistance in P. aeruginosa.

Amino Acid Sequence↗

Mobile gene cassettes and integrons in evolution.

Integrons and the site-specific recombination systems encoded by them provide a simple mechanism for the addition of new genes to bacterial chromosomes. Although there is substantial divergence among the four known integron-encoded integrases, they all recognize the recombination sites, known as 59-base elements, that are associated with genes that are packaged in gene cassettes. In contrast, the integron-associated recombination sites, attl sites, are preferentially recognized by the cognate integrase.

Base Sequence↗

The influence of femoral head surface roughness on the wear of ultrahigh molecular weight polyethylene sockets in cementless total hip replacement.

A theoretical relationship was recently proposed relating the wear behavior of polymetric bearing materials articulating against hard counterfaces.(1) This model attempts to predict the influence of surface roughness on wear. Laboratory-based studies have been used to establish the validity of these relationships, but their application to the clinical situation has not been investigated fully. Forty-two retrieved PCA hip joints have been assessed. The total wear volume was calculated from the penetration measured using the shadowgraph method, and roughness of the articulating surfaces was recorded using noncontacting profilometry. The roughness of the explanted femoral heads was observed to increase (median S(a) - 10. 35 nm worn region, 3.05 nm peripheral region), while that of the acetabular liner fell dramatically (median S(a) - 41 nm worn region, 212 nm unworn region). No evidence of a relationship between the topography of the worn regions of the femoral head and that of the acetabular liner could be found. Similarly, the strength of the association between the surface roughness and the clinical wear factor was considerably poorer than that achieved in laboratory experiments. A number of reasons for this observation are proposed. Most deleterious was considered to be the inability of the roughness parameters to describe the damaging features of the surface adequately. Uncertainty as to when the surface of the component degrades during its life serves to introduce further doubt as to the application of the wear models in the clinical environment. In conclusion, this study fails to provide clinical evidence to substantiate the relationship between surface finish and wear rate. The adoption of standardized measurement parameters and techniques would facilitate the direct comparison of joint types and the selection of the most advantageous materials.

Arthroplasty, Replacement, Hip↗

Transposon Tn21, flagship of the floating genome.

The transposon Tn21 and a group of closely related transposons (the Tn21 family) are involved in the global dissemination of antibiotic resistance determinants in gram-negative facultative bacteria. The molecular basis for their involvement is carriage by the Tn21 family of a mobile DNA element (the integron) encoding a site-specific system for the acquisition of multiple antibiotic resistance genes. The paradigm example, Tn21, also carries genes for its own transposition and a mercury resistance (mer) operon. We have compiled the entire 19,671-bp sequence of Tn21 and assessed the possible origins and functions of the genes it contains. Our assessment adds molecular detail to previous models of the evolution of Tn21 and is consistent with the insertion of the integron In2 into an ancestral Tn501-like mer transposon. Codon usage analysis indicates distinct host origins for the ancestral mer operon, the integron, and the gene cassette and two insertion sequences which lie within the integron. The sole gene of unknown function in the integron, orf5, resembles a puromycin-modifying enzyme from an antibiotic producing bacterium. A possible seventh gene in the mer operon (merE), perhaps with a role in Hg(II) transport, lies in the junction between the integron and the mer operon. Analysis of the region interrupted by insertion of the integron suggests that the putative transposition regulator, tnpM, is the C-terminal vestige of a tyrosine kinase sensor present in the ancestral mer transposon. The extensive dissemination of the Tn21 family may have resulted from the fortuitous association of a genetic element for accumulating multiple antibiotic resistances (the integron) with one conferring resistance to a toxic metal at a time when clinical, agricultural, and industrial practices were rapidly increasing the exposure to both types of selective agents. The compendium offered here will provide a reference point for ongoing observations of related elements in multiply resistant strains emerging worldwide.

Base Sequence↗

Prevalence of impingement in explanted Charnley acetabular components.

: Impingement of the femoral neck against the rim of the socket bore has often been cited as one of the contributory factors in the acetabular loosening process. However, there has been little research on its clinical prevalence or on the effects of both linear wear and the diameter of the femoral neck. With this aim in mind, 74 Charnley prostheses were examined after being removed at revision surgery and the sockets interrogated for evidence of impingement. The probability of impingement was assessed using logistic regression analysis. A strong positive association was observed between penetration depth and impingement (chi2 = 12.8; P = 0.0004) regardless of differences in the femoral neck diameter. Further, the introduction of femoral components which comprised a reduced diameter neck had a positive effect, in that the 50% probability of impingement occurred at approximately 2 mm of penetration. For those components with standard necks, the 50% probability of impingement occurred at zero mm of penetration. If impingement is a problem then a reduced diameter neck would appear to be a solution in cutting rates of long-term loosening. However, whether or not this reduction in rim damage, and therefore impingement, is clinically significant in terms of loosening can only be fully assessed from long-term survival analysis and comparison with autopsy retrieved specimens.

Acetabulum↗

Differences in the rates of penetration determined from radiographic and shadowgraphic measurements of acetabular sockets.

A number of previous studies have observed a marked difference in the penetration depths recorded between direct and radiographic measurement, although no assessment of how these discrepancies affect the rates of penetration has been undertaken. In this report, the penetration depth of 95 sockets was determined from both prerevision radiographs and casts of the retrieved sockets using the uniradiographic and shadowgraphic techniques, respectively. It was observed that the mean discrepancy between the penetration rates derived from the two measurement methods was 0.046 (SE 0.017) mm yr(-1), which was significantly different from zero at P = .007. It was concluded that the penetration rates derived from this method of radiographic assessment seriously underestimated the true value as measured by a direct method by approximately 20%. As a consequence, the discrepancy in penetration rates between those sockets that are loose at revision surgery (direct measurement) and the general population of acetabular components (radiographic measurement) may not be as large as previously thought.

Acetabulum↗

Wear in retrieved acetabular components: effect of femoral head radius and patient parameters.

Forty-seven explanted Porous Coated Anatomic (PCA, Howmedica, Rutherford, NJ) cementless acetabular components were acquired at revision surgery. All the components articulated against CoCrMo femoral heads of 32-mm diameter. The penetration depth and angle were measured using the shadowgraph technique. The wear volume was then calculated using Kabo's formula. Using weighted linear regression analysis, the mean penetration rate and mean volumetric wear rate were calculated to be 0.23 (SE, 0.03) mm3/y and 96 (SE, 13) mm3/y, respectively. The creep component was not found to be significantly different from zero. The clinical wear factor, k(clinical), for this cohort was also calculated using linear regression analysis but with the assumption that creep was zero. The value found, k(clinical) = 1.93 (SE, 0.29) x 10(-6) mm3/N-m, was similar to those in previous studies involving cemented joints with a 22-mm femoral head diameter. The similar k(clinical) values of these substantially different joint types suggest that the high volumetric wear rate for the PCA joint can be attributed entirely to its larger head size and the younger, more active, patient profile. Fixation technique and metal backing seem not to influence the rate of wear.

Acetabulum↗

Binding of the purified integron DNA integrase Intl1 to integron- and cassette-associated recombination sites.

The site-specific recombinase Intl1, encoded by class 1 integrons, catalyses the integration and excision of gene cassettes by recognizing two classes of sites, the integron-associated attl1 site and the 59-base element (59-be) family of sites that are associated with gene cassettes. Intl1 includes the four conserved amino acids that are characteristic of members of the integrase family, and Intl1 proteins with single amino acid substitutions at each of these positions had substantially reduced catalytic activity, consistent with this classification. Intl1 was purified as a fusion protein and shown to bind to isolated attl1 or 59-be recombination sites. Binding to attl1 was considerably stronger than to a 59-be. Binding adjacent to the recombination cross-over point was not detected. A strong Intl1 binding site within attl1 was localized by both deletion and footprinting analysis to a 14 bp region 24-37 bp to the left of the recombination cross-over point, and this region is known to be critical for recombination in vivo (Recchia et al., 1994). An imperfect (13/15) direct repeat of this region, located 41-55 bp to the left of the recombination cross-over point, contains a weaker Intl1 binding site. Mutation of the stronger binding site showed that a single base pair change accounted for the difference in the strength of binding.

Amino Acid Sequence↗