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Biomedical subjects

R D Fraser

Publications and source records attributed to R D Fraser.

At least 91 records · Page 5Linked to original sources

Fractures and fractures-dislocations of the lumbar spine. A retrospective study of 70 patients.

A retrospective study was undertaken to analyse and compare the results of Harrington instrumentation with postural reduction and nursing in patients with fractures and fracture-dislocations of the lumbar spine. Thirty patients were treated by postural reduction and nursing, and 38 underwent early surgical reduction and internal fixation with Harrington instrumentation, together with a posterior fusion in three patients and an anterior fusion at the level of the fracture in another two patients. External splintage was used in only one patient in the series. At an average follow up of 5.9 years, bony deformity quantified by angulation, displacement and the vertebral wedge index was greater in the conservative group than in the group treated surgically. No significant difference was observed in comparing the rates of neurological recovery in the two groups. At follow up, patients with no symptoms had less severe bony deformity. Loss of fixation of Harrington instrumentation occurred in 46% of patients treated by this method. The incidence of other complications was not significantly different in the two groups. Despite the unacceptably high rate of local complications, Harrington instrumentation achieved better correction of bony deformity than postural reduction and nursing, prevented progression of deformity and decreased the incidence of symptoms at follow up. This study indicates that in these injuries bony deformity can be satisfactorily corrected by early Harrington instrumentation alone, without spinal fusion and bracing, provided an exacting surgical technique is employed.

Adolescent↗

Discitis after discography.

Infection after intradiscal injections has been recognised as a distinct entity, but discitis after discography has often been attributed to an aseptic process or a chemical reaction to the contrast material. We examined the hypothesis that discitis after discography is always due to infection, and report a clinical review and an experimental study. Part I. We reviewed the case records and radiographs of 432 patients who had undergone lumbar discography. When an 18-gauge needle without a stilette had been used, discitis was diagnosed in 2.7% of 222 patients but stiletted needles and a two-needle technique at each level reduced the incidence to 0.7%. Seven patients with discitis after discography had undergone anterior discectomy and fusion; in them the histopathological findings were of a chronic inflammatory response. Bacteria were isolated from the discs of three of the four patients who had open biopsy less than six weeks from the time of discography. These findings suggest that bacteria were initiators rather than promoters of the response. Part II. Multiple level lumbar discography was carried out in mature sheep, injecting contrast material with or without various concentrations of bacteria. Radiographs were taken and the discs and end-plates were examined histologically and cultured for bacteria at intervals after injection. None of the controls showed any evidence of discitis but all sheep injected with bacteria had typical radiological and histopathological changes by six weeks, though cultures were almost all negative. However, at one and two weeks after injection, but usually not after three weeks, bacteria could be isolated. We suggest that all cases of discitis after discography are initiated by infection, and that a very strict aseptic technique should be used for all injections into intervertebral discs.

Adolescent↗

Molecular mobility in the gap regions of type I collagen fibrils.

Recent studies of the structure of Type I collagen fibrils (Piez and Trus, Biosci. Rep. 1:801-810, 1981; Fraser, MacRae, Miller and Suzuki, J. Mol. Biol. 167:497-521, 1983) suggest that the segments of the collagen molecule which comprise the gap region are more mobile than those which comprise the overlap region. We have analyzed the distribution of amino acid residues and triplet types between the two regions, and find significantly non-uniform distributions for Ala, Gln, His, Hyp, Leu, Phe, and Tyr, and for triplets containing two imino acid residues. Taken together with the lower packing density in the gap region these observations provide a basis for understanding the greater mobility of the molecular segments in the gap region. In addition, we have examined the linear distribution of residue types in the two regions and also the hydropathy profile (Kyte and Doolittle, J. Mol. Biol. 157: 105-113, 1982). These reveal a segment of the gap region comprising helical residues 165-173, 399-407, 633-641 and 867-975 which has the highest hydropathy index, is devoid of charged residues, and contains very high proportions of Ala, Hyp and Phe.

Amino Acid Sequence↗

Intermediate filaments in alpha-keratins.

Previous x-ray diffraction studies on the alpha-keratins of hair and wool have revealed that the intermediate filaments (IF) have a helical structure rendered imperfect by a precisely defined dislocation. It has also been possible to deduce a surface lattice for the IF and to determine the number of IF molecules associated with each lattice point. In this work this information is combined with data on the ionic interactions between the coiled-coil rope segments of the IF molecules to provide a plausible model for the pattern of interactions that stabilize the framework of the IF in the "hard" alpha-keratins. Similar interaction studies of the proteins from the IF in the so-called "soft" alpha-keratin from the stratum corneum layer of the skin suggest that they are likely to have an essentially similar pattern.

Animals↗

Discitis following chemonucleolysis. An experimental study.

Although infection following intradiscal injections has been recognized as a distinct entity, discitis following chemonucleolysis has been often attributed to a chemical reaction from chymopapain. In the first part of this study the effect of chymopapain and Conray 280 on a wide range of bacteria was measured in vitro. Chymopapain was found to have a bactericidal effect on all bacteria tested, which was more pronounced with gram positive organisms, whereas Conray 280 showed very little if any antibacterial effect after 48 hours. The aim of the second part of the study was to test the hypothesis that discitis following intradiscal chymopapain injection is due to infection and not to a chemical reaction. Multiple level lumbar intradiscal injections were carried out in eight mature sheep. Sixteen discs in four sheep were injected with a mixture of reconstituted chymopapain and a Staphylococcus epidermidis suspension. Sixteen discs in another four sheep were injected with reconstituted chymopapain only. All sheep were sacrificed at 6 weeks and the discs and end-plates were examined radiologically, and by histopathology and nuclear material was cultured for bacteria. None of the controls showed any evidence of discitis, whereas all sheep injected with bacteria had typical radiologic and histopathologic changes of discitis. However, in most cases in which end-plate lesions were well established there was no evidence of bacteria at sacrifice. These findings support the opinion that discitis following intradiscal injection is always due to infection introduced by the needle tip.

Animals↗

The structure of collagen.

A knowledge of the structure of collagen fibrils is important for any rational discussion of the occurrence and treatment of fibrosis. The different genetic types of collagen, and the structure of the triple-helical molecule as refined from X-ray fibre diffraction data, are described. The problem of determining molecular arrangement in native tissues is discussed. The various models proposed for the molecular arrangement of type I collagen are compared and an account is given of the quasi-hexagonal model. A detailed analysis of the X-ray diffraction patterns from native type I collagen fibres is used to provide a quantitative description of the quasi-hexagonal model. Parameters such as molecular positions, azimuthal orientation and axial shift can be estimated from the diffraction patterns. These parameters refer to the helix main-chain. Side-chain conformations can then be built in by molecular graphics and the predicted X-ray pattern for the complete model compared with the observed pattern.

Animals↗

Intermediate filament structure.

In a previous communication (Biosci. Rep. 3, 517-525, 1983) we described quantitative X-ray diffraction studies of alpha-keratin which were shown to be consistent with the presence of finite arrays of repeating units, successive arrays being set down at axial intervals of 470 A. In addition the axial interval between repeating units in an array was shown to be 197.9 A. It was suggested that this could most readily be explained by supposing that a surface lattice was present which contained a dislocation along a helical path with unit height h = 470 A and unit twist magnitude of t = 49.1 degrees. The number of repeating units was shown to be in the range 7-9. With 7 repeats the mismatch of the lattice along the dislocation is small and this choice was used to develop a detailed model for the filament. Subsequent studies of molecular interactions have shown however that the coiled-coil rope segments in the rod domain of the molecule are most probably oriented parallel to the dislocation, and so minimization of lattice mismatch may be less important than originally supposed. In the present communication it is shown that the choice of 8, rather than 7, for the number of repeating units yields a model which is more compatible with estimates of the linear density and also provides the basis for a general model for polymorphism in intermediate filament lattices.

Animals↗

Molecular conformation and packing in collagen fibrils.

New X-ray diffraction data have been collected from specimens of tendon collagen stained with phosphotungstic acid. Measurements of the positions of the Bragg reflections associated with the crystalline lattice provide, for the first time, a complete description of the unit cell. A strong band of intensity in the molecular transform associated with the pitch of the molecular helix can be identified and a detailed analysis of the intensities and positions of the Bragg reflections in this band has been carried out. The principal conclusions are that the portions of the collagen molecule that contribute to these reflections have a common direction; that they have a length very much less than that of a complete molecule; that the paths of the individual portions through the crystal are incompatible with a completely straight molecule, and that the molecule is therefore crimped. No evidence was obtained for a second series of Bragg reflections attributable to a second set of molecular portions linking the first set, and it is concluded that the linking set is more mobile and subject to positional variation from cell to cell. The most plausible explanation of our finding is that the first set corresponds to the portions of the molecules in the overlap zone and the second set to the portions in the gap zone. A detailed analysis of the Bragg reflections in the strong band of intensity associated with the pitch of the molecular helix has provided information about the relative azimuthal orientations and the lateral positions in the unit cell of the five molecular segments in the overlap zone. None of the existing models for fibril structure accounts satisfactorily for all the results obtained in the present studies and alternative models are developed and tested.

Animals↗

The structure of the alpha-keratin microfibril.

Quantitative measurements of the intensity of the meridional reflections in the X-ray-diffraction pattern of alpha-keratin are shown to be consistent with a microfibril structure in which a surface lattice with an axially projected period around 200 A is subject to a periodic interruption with an axially projected period of 470 A. Taken in conjunction with recent evidence on the chemical structure of alpha-keratin and other intermediate filaments this finding enables an elaboration to be made of a model proposed earlier by RDB Fraser, TP MacRae, & E Suzuki (J. Mol. Biol. 108, 435-452, 1976) for the alpha-helical framework of the microfibril. The disposition and connectivity of the helical segments suggested here provides a straightforward explanation of a number of recent physicochemical and electron-microscopical observations on intermediate filaments and provides a starting point for the development of models for the framework of other intermediate filaments.

Keratins↗

Molecular structure and mechanical properties of keratins.

Keratinized epidermal appendages have mechanical properties which are typical of those expected for composite materials with a filament-matrix texture. At 100% relative humidity the matrix is highly hydrated, mechanically weak and exhibits viscoelastic behaviour. As the water content is reduced the matrix becomes progressively stiffer until at 0% relative humidity its properties approach those of the filaments. In the normally encountered range of relative humidities the advantages of such a texture are that stress is evenly distributed over the filaments, which constitute the load-bearing elements, thus preventing the propagation of cracks from local imperfections. Based on studies of synthetic filament-matrix composites potentialities for the adaptation of the mechanical properties to specific functions are to be found in variation of the properties of the filaments and the matrix and also of the cross-linking. Since keratin is a filament-matrix composite at the molecular level the great diversity of molecular species presumably has its origin in such adaptation. Superimposed on filament and matrix composition and properties are the variables of filament orientation and proportion and there is abundant evidence that many of the subtler properties of keratinized appendages stem from variations in these factors.

Animals↗

Ipsilateral fracture of the femur and tibia.

The hospital records of 222 cases of ipsilateral fractures of the femur and tibia were reviewed, and patients were grouped according to the type of fracture and the method of treatment. Thirty-five per cent of patients required late operation for delayed union or non-union, osteomyelitis, refracture and malunion, regardless of the treatment group. A disturbing factor was the 30% incidence of osteomyelitis in patients treated by fixation of both fractures, almost three times the incidence when only one fracture was fixed. A 30% incidence of delayed union or non-union occurred in patients managed conservatively. Of sixty-three patients personally examined, the worst results found were those following conservative management of both fractures. More use of rigid external fixation and of cast bracing is recommended in the management of the fractured tibia, combined with internal fixation of the femoral fracture. Examination of the knee suggested that, with ipsilateral fractures, disruption of ligaments is a common occurrence and should always be suspected.

Adolescent↗

Orthopaedic aspects of spinal tumors in children.

A retrospective survey has been made of forty children with spinal tumours. Difficulties in establishing the correct diagnosis are mentioned and the value of radiological and cerebrospinal fluid investigations discussed. The major orthopaedic disabilities are spinal deformity or instability, and paraplegia. The main factor in the development of the former is the site of laminectomy: the higher the level the greater is the likelihood of deformity or instability developing. Measures to prevent this distressing complication are discussed. The role of the orthopaedic surgeon in the management of these children is emphasised.

Adolescent↗