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Biomedical subjects

R M Hall

Publications and source records attributed to R M Hall.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

Antibiotic resistance in gram-negative bacteria: the role of gene cassettes and integrons.

Resistance of gram-negative organisms to antibiotics such as beta-lactams, aminoglycosides, trimethoprim and chloramphenicol is caused by many different acquired genes, and a substantial proportion of these are part of small mobile elements known as gene cassettes. A gene cassette consists of the gene and a downstream sequence, known as a 59-base element (59-be), that acts as a specific recombination site. Gene cassettes can move into or out of a specific receptor site (attl site) in a companion element called an integron, and integration or excision of the cassettes is catalysed by a site-specific recombinase (Intl) that is encoded by the integron. At present count there are 40 different cassette-associated resistance genes and three distinct classes of integron, each encoding a distinct Intl integrase. The same cassettes are found in all three classes of integron, indicating that cassettes can move freely between different integrons. Integrons belonging to class I often contain a further antibiotic resistance gene, sull, conferring resistance to sulphonamides. The sull gene is found in a conserved region (3'-CS) that is not present in all members of this class. Class I integrons of the sull type are most prevalent in clinical isolates and have been found in many different organisms. Even though most of them are defective transposon derivatives, having lost at least one of the transposition genes, they are none the less translocatable and consequently found in many different locations. The transposon Tn7 is the best known representative of class 2 integrons, and Tn7 and relatives are also found in many different species.

Journal Article↗
PubMed1998

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↗
PubMed1998

Discrepancy between penetration depths derived from radiographic and direct measurement of acetabular components.

The most common technique for assessing penetration due to wear in acetabular components is with the aid of the most recent serial radiograph. This approach, which is often termed the uni-radiographic method, has been shown to underestimate the more reliable value of the penetration depth deduced from direct measurement of explanted sockets. In this article the causes of the discrepancies between the two data sets are explored. Ninety-six sockets were available from revision surgery for which both the penetration depth and angle could be measured using the shadowgraphic technique in both the coronal and wear planes. Further, the penetration depth for each of the sockets was also assessed from pre-revision X-rays. A significant discrepancy was observed between the penetration depths measured in the wear plane of the replica delta Pw and that measured from the radiograph, delta PX-ray. The discrepancy was greatest for loose sockets as opposed to those that were still fixed at revision surgery. Using the corresponding data from the shadowgraph measurements, it was possible to deduce that the errors have arisen from the radiographic measurement of wear in the coronal plane and the formula used in calculating delta PX-ray. If these errors (which cannot be calculated from the X-ray data alone) were taken into consideration, then the systematic bias between radiographic and shadowgraphic measurement was greatly reduced. The largest portion of the discrepancy was accounted for by wear occurring out of the plane of the radiograph, and this, in general, coincides with the coronal plane. Overall, these results indicate that the accurate measurement of wear from serial radiographs is not possible and that improved performance in terms of accuracy can only be achieved when a three-dimensional system is used. An alternative method for deducing the radiographic penetration depth is proposed which, theoretically, negates the error arising from the inaccuracy of the formula.

Acetabulum↗
PubMed1998

The association between rates of wear in retrieved acetabular components and the radius of the femoral head.

Current evidence suggests that loosening of the acetabular socket is related to the volume of ultra-high molecular weight polyethylene wear debris generated at the articulating surfaces, through a process of bone resorption. Therefore it is important that the rate of volumetric wear is minimized in an attempt to extend the useful life of the procedure. Laboratory evidence indicates that a reduction in sliding distance would be beneficial in achieving this target and may be attained by a reduction in femoral head radius. To investigate the relationship between femoral head size and the rates of both volumetric wear and penetration, 200 acetabular components were retrieved at the time of revision surgery. The joints had femoral heads ranging in size from 11.1 to 19.8 mm radius. For those sockets that were loose at revision surgery, a significant correlation was observed, between the rate of volumetric wear and the radius of the femoral head. For this cohort an increase in radius of 1 mm resulted in an increased rate of volumetric wear of 5.1 (SE 1.4) mm3/yr. However, the explained variance in the regression was low and exemplifies the multifactorial nature of the wear process. In particular, it is anticipated that the activity of the patient will have a significant effect on the rate at which the debris is produced. No significant correlation was observed between the rate of linear wear and femoral head radius. These results would indicate a benefit in using head sizes of a smaller radius, which generate debris at a reduced rate, and therefore require more time to accumulate large volumes of wear products.

Aged↗
PubMed1998

The frictional behaviour of explanted PCA hip prostheses.

The frictional characteristic of 22 explanted and two unused PCA total hip arthoplasties were assessed using the Durham hip simulator. The friction of the explanted joints was not found to be significantly different from that of the unused joints. In contrast, explanted Charnley joints often exhibit increased frictional characteristics. This discrepancy is accounted for by the lack of cement ingression in the PCA design.

Adult↗
PubMed1998

Stem fixation in the Charnley low-friction arthroplasty in young patients using an intramedullary bone block.

We report a prospective study of the use of intramedullary bone blocks to improve the fixation of a matt-finish femoral stem in Charnley low-friction arthroplasties. There were 379 patients (441 hips), but at a minimum follow-up of ten years there were 258 arthroplasties in 221 patients including some which had been revised. The mean age at surgery was 41 years (17 to 51) and the mean follow-up was 13.4 years (1 to 20 including the early revisions). Nine stems (3.5%) had been revised for aseptic loosening, but there were no stem fractures. Survivorship of stems was 99.2% at ten years and 94.35% at 15 and 20 years. We found that the patient's gender, the position of the stem and the experience of the surgeon all influenced the outcome. Our findings suggest that using our method of stem fixation, follow-up of over 11 years was needed to reveal the effects of endosteal cavitation of the femur, and of over 13 years to assess any divergence between the clinical and the radiological outcomes of stem fixation.

Adolescent↗
PubMed1998

Observations on the direction of wear in Charnley sockets retrieved at revision.

The direction of wear in the acetabular socket has implications for the amount of debris that is generated during movement, for the magnitude of eccentric loading and for the incidence of impingement of the neck. We observed the direction of penetration with respect to a global co-ordinate system in 84 acetabular components retrieved at reoperation. The mean direction of wear relative to the open face of the sockets was found to be 37 degrees with a range from 0 degrees to 87 degrees. For those values determined using the inclination of the socket on the prerevision radiograph, the mean direction of penetration in the coronal plane had a lateral, rather than a medial, component. The mean angle was 84 degrees (SD 17 degrees) with respect to the horizontal. The angle of penetration was found to correlate significantly with the depth, in that the lateral component became larger as the wear progressed. There was also a significant correlation between the rate of penetration and the direction of wear. Despite the theoretical advantage of penetration in the superolateral direction, i.e., along the margin of the socket, in reducing the probability of impingement of the neck, no significant correlation was seen between the angle of penetration and the period of use in vivo. This may suggest that impingement of the femoral neck on the rim of the socket may not be the dominant factor in loosening of the socket but can still be important in a few cases.

Acetabulum↗
PubMed1998

Treatment of the wounded at Chipyong-ni.

The battle fought by a U.S.-French force at Chipyong-ni in mid-February 1951 has been called the turning point of the Korean War, and may have been the first time that transfusions of whole blood were given as far forward as the regimental area during combat. The surgeon, or chief medical officer, of the United Nations force at Chipyong-ni describes this and other measures required by the tactical and medical situations there, and illustrates how they were made possible, in large part, because an important lesson learned during World War II had been applied: the surgeon had direct access to the commander as a member of his staff, and controlled the task force medical facilities.

Blood Transfusion↗
PubMed1997

Mobile gene cassettes and integrons: moving antibiotic resistance genes in gram-negative bacteria.

In Gram-negative pathogens, multiple antibiotic resistance is common and many of the known resistance genes are contained in mobile gene cassettes. Cassettes can be integrated into or deleted from their receptor elements, the integrons, or infrequently may be integrated at other locations via site-specific recombination catalysed by an integron-encoded recombinase. As a consequence, arrays of several different antibiotic resistance genes can be created. Over 40 gene cassettes and three distinct classes of integrons have been identified to date. Cassette-associated genes conferring resistance to beta-lactams, aminoglycosides, trimethoprim, chloramphenicol, streptothricin and quaternary ammonium compounds used as antiseptics and disinfectants have been found. In addition, most members of the commonest family of integrons (class 1) include a sulfonamide resistance determinant in the backbone structure. Integrons are themselves translocatable, though most are defective transposon derivatives. Integron movement allows transfer of the cassette-associated resistance genes from one replicon to another or into another active transposon which facilitates spread of integrons that are transposition defective. Horizontal transfer of the resistance genes can be achieved when an integron containing one or more such genes is incorporated into a broad-host-range plasmid. Likewise, single cassettes integrated at secondary sites in a broad-host-range plasmid can also move across species boundaries.

Anti-Bacterial Agents↗
PubMed1997

Friction in hip prostheses.

Although the reduction of frictional torques was the driving force behind the design of the Charnley prosthesis, later concerns about wear and subsequent loosening of this and other hip replacements have dominated debate within the bioengineering community. To stimulate discussion on the role of friction in loosening, a review of the frictional characteristics of different prostheses was undertaken. The use of simple laboratory screening-type machines in the frictional assessment of different material combinations is discussed together with experiments performed on single axis simulators using both conventional and experimental prostheses. In particular, recent developments in the use of soft layer components are highlighted. Further, the possible link between excessively high frictional torques and loosening is discussed in the light of current results obtained from explanted prostheses.

Alloys↗
PubMed1997

Origins of the mobile gene cassettes found in integrons.

Many of the acquired antibiotic resistance genes found in enterobacteria and pseudomonads are part of small mobile elements known as gene cassettes, and other genes are also likely to be found in cassettes. The origins of the genes and the recombination sites that make up cassettes are not known, but recent analyses of available data suggest that cassettes may be ancient structures, and some hypotheses for how they are formed can now be examined.

DNA Transposable Elements↗
PubMed1997

The effect of surface topography of retrieved femoral heads on the wear of UHMWPE sockets.

The study was undertaken to investigate the association, if any, between the surface roughness of 35 explanted femoral heads and the clinical wear factors of the corresponding polyethylene sockets. The wear of the socket was measured using a shadowgraph technique. The surface topography was investigated using a Rodenstock RM 600 non-contacting profilometer, and six parameters were used to characterise the roughness. Further, qualitative inspections of the femoral surface were undertaken using both a Joel JSM-IC-848 scanning electron microscope and a Zeiss Axiotech microscope with a differential interference contrast facility. Two parameters were found to correlate with the clinical wear factor, namely the skewness of the amplitude distribution function, Sk, and the arithmetic mean roughness, Ra. Simple parameters describing the peak heights of the asperities were found not to have a significant association with the clinical wear factor. The exponent in the power relationship between the arithmetic mean roughness and kclinical was found to be equal to 0.5 (SE: 0.2). This value is significantly smaller than that found in laboratory experiments and may be due to the non-uniform nature of the roughening of the femoral head, three-body wear and the effect of other clinical factors on the wear process. Further, extremely strong correlations were detected between the differing roughness parameters, which would suggest that any attempt to deduce which one is the most important in affecting the wear of the polymeric counterface is fraught with difficulty. However, further investigation of those parameters, such as the reduced peak height or the material filled profile peak area, which may better describe the effect of the counterface on the wear of the UHMWPE surface would appear to be prudent.

Hip Prosthesis↗
PubMed1997

Structure and function of 59-base element recombination sites associated with mobile gene cassettes.

The integration of gene cassettes into integrons is effected by site-specific recombination catalysed by an integrase, IntI, encoded by the integron. The cassette-associated recombination sites, 59-base elements, are not highly conserved and vary in length from 57 to 141 bp. They can be identified by their location and the relationship of over 20 bp at their outer ends to consensus sequences that are imperfect inverted repeats of one another. The recombination cross-over occurs close to one end of the 59-base element, within a conserved core site with the consensus sequence GTTAGGC or GTTRRRY. By introducing single-base changes at each of these positions in the aadB 59-base element, bases that are critical for site activity were identified. The recombination cross-over was also localized to a unique position between the adjacent G and T residues. Changes introduced in the conserved AAC of the inverse core site (GCCTAAC or RYYYAAC) located at the opposite end of the 59-base element also reduced site activity but to a lesser extent. Sequences of rare recombinants revealed an alternative position for strand exchange and led to the conclusion that 59-base elements comprise two simple sites, analogous to those recognized by other integrases, with each simple site made up of a pair of inversely oriented IntI binding domains separated by a spacer of 7 or 8 bp. Re-examination of the sequences of all known 59-base elements revealed that this simple site configuration was present at both the left and right ends in all 59-base elements. The identity of bases in the spacer is not required for efficient recombination and the cross-over is located at one end of the spacer, suggesting that during IntI1-mediated recombination only one strand exchange occurs.

Base Composition↗