Search PubMedSearch

Biomedical subjects

S P Hughes

Publications and source records attributed to S P Hughes.

At least 19 recordsLinked to original sources

Instantaneous center of rotation and instability of the cervical spine. A clinical study.

STUDY DESIGN: This study was designed to investigate flexion and extension of the cervical spine in patients with "instability" of the cervical spine. OBJECTIVES: To establish a new method of calculating the instantaneous center of rotation (ICR) of the skull relative to the thorax and to compare the differences in the ICR between normal volunteers and patients. SUMMARY OF BACKGROUND DATA: "Instability" of the cervical spine commonly is investigated using functional radiographs, which is an unreliable method. Although the ICR was suggested as an objective parameter in measuring spinal "instability," the ICR of the skull relative to the thorax has not been studied before. METHOD: Three groups of subjects (27 normal volunteers, 28 patients with chronic cervical spondylosis, and 17 patients undergoing fusion for cervical disc degeneration) were measured with a CA-6000 system (OSI, CA). The ICR then were calculated and compared at various angles of flexion and extension. RESULTS: The horizontal component of the ICR in the preoperative group was found to have shifted anteriorly from 5 degrees to 25 degrees of flexion (P < 0.05) and at 5 degrees of extension (P < 0.05), compared with that of the healthy subjects. There also was a significant difference in the vertical component of the ICR at 15 degrees of flexion (P < 0.05). However, there were no significant differences in the horizontal and the vertical components of the ICR between the normal and nonoperative groups. CONCLUSION: The ICR in patients with "instability" of the cervical spine was found to have shifted anteriorly; the method described in this study might be useful for identifying patients who suffer from this condition.

Aged

Quantitative assessment of the motion of the lumbar spine in the low back pain population and the effect of different spinal pathologies of this motion.

There are few objective means by which disability caused by low back pain (LBP) can be quantified. The purpose of this study was to investigate the usefulness of motion measurements in the assessment of LBP. The motion characteristics of 138 LBP subjects were investigated, and the data compared with a previously published database of normal subjects. Values of range of motion and angular velocity were obtained for all subjects in each plane of motion. Analysis of these motion characteristics demonstrated significant differences (P < 0.0001) between the two populations; however both populations demonstrated considerable intersubject variation. Multiple regression analysis revealed that some of the variance in the LBP population was attributable to the underlying diagnosis. Patients with a spondylolisthesis tended to be hypermobile whilst those with spinal stenosis, disc prolapse or degenerative disc disease tended to be hypomobile. All diagnostic groups showed impairments in their velocity characteristics.

Adult

Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease.

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects. We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease.

Adolescent

Aseptic loosening of total hip replacement. Macrophage expression of inducible nitric oxide synthase and cyclo-oxygenase-2, together with peroxynitrite formation, as a possible mechanism for early prosthesis failure.

Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E2 (PGE2), as an indicator of COX-2 activity, was measured using an enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68+ macrophages. The presence of calcium-independent iNOS activity and PGE2 production was confirmed in the homogenised interface membrane. Immunocytochemistry showed that periprosthetic CD68+ wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68+ macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68+ macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and PGE2 have been implicated in the induction and maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening.

Adolescent

[Morphologic effect of adrenaline and insulin on bone capillaries after receptor blockade. Functional transmission electron microscopy analysis].

In three groups of six mice each, the alpha- and beta-receptors were blocked by phentolamine and propranolol. The mice in the three groups then received an intravenous bolus injection of saline solution, epinephrine, and insulin, respectively. Cortical bone capillaries from the tibia diaphysis were submitted to transmission electron microscopy (TEM). The lumen and endothelium were measured and the results compared. Significant changes were only noted in the endothelium after the administration of insulin. These findings suggest that there are also insulin receptors in bone. Furthermore, they support previous findings in similar studies with epinephrine.

Adrenergic alpha-Antagonists

Motion characteristics of the lumbar spine in the normal population.

STUDY DESIGN: The present study investigated the dynamic motion characteristics of the lumbar spine in the normal population using a potentiometric analysis system. OBJECTIVES: To assess the ability of a triaxial potentiometric analysis system to measure dynamic motion in the lumbar spine, and to use this system to form a database of dynamic motion characteristics from which normal parameters of motion and the factors affecting this motion could be defined. SUMMARY OF BACKGROUND DATA: Spinal motion has been studied using a variety of different methods, the majority of which have been limited either in terms of reliability, accuracy, or invasiveness and many have been only of a static nature. There has been no previous study into the normal dynamic motion characteristics of the lumbar spine. METHODS: The accuracy of the system was determined by a series of tests against a calibrated engineering mill, and the reliability of the system was assessed on 10 subjects with repeated measurements over a 3-day period. Values of range of motion and angular velocity were obtained from 203 normal subjects during flexion and extension, lateral flexion, and rotation. RESULTS: The results of the calibration testing revealed excellent accuracy, and it was shown that the system was repeatable. Initial analysis of the results indicated that sex differences did exist with men having 58.4 degrees of flexion and women having 53.4 degrees. Age appeared to have an influence on motion, and a gradual reduction was seen with each decade (P < 0.001), with the 20-29-year age range having 59.5 degrees mean flexion, the 30-39-year group having 58.1 degrees, the 40-49-year group having 53.7 degrees, the 50-60-year group having 57.5 degrees, and the 60-70-year group having 45.9 degrees. Multiple regression techniques revealed that only a few factors are important with respect to motion and that these varied according to the characteristic being defined. CONCLUSIONS: Range of motion tended to be affected by age and sex, whereas velocity was only affected by distance moved, with occupation and body mass index having little or no influence on the motion. The factors identified could only account for a small proportion of the variation seen, suggesting that it is difficult to predict the motion characteristics with any degree of sensitivity.

Adult

Relations between upper limb soft tissue disorders and repetitive movements at work.

To make a preliminary assessment of whether upper limb soft tissue disorders might be associated with activities at work, we have conducted a case-control study of subjects attending orthopedic clinics in three cities. All subjects between the ages of 16 and 65 years, in whom defined soft tissue conditions of the upper limb were diagnosed by the participating orthopedic surgeons, were invited to take part. Controls were subjects attending the same clinics within the same age range whose clinical diagnosis did not include disease of the upper limb, cervical or thoracic spine. Information concerning repetitive movements of the upper limbs at work was elicited by questionnaire. Five hundred eighty cases and 996 controls were studied, representing 96% and 93%, respectively, of those invited to participate. The diagnoses of the cases included soft tissue conditions affecting the shoulder, elbow, forearm, wrist, thumb, hand, and fingers. The diagnoses of the controls included traumatic, degenerative, and inflammatory conditions, mostly of the legs and lower back. Women predominated among the cases (70%) and men among the controls (56%). Of 221 female cases with injury to the wrist and forearm, 32 were cleaner/domestics (14.5%) compared to 35 to 439 controls (8%), a difference statistically significant at the 2 1/2% level. Other jobs significantly overrepresented (5% level) among female cases with injuries at various anatomical sites included hairdressers, secretary/temps, assembly line workers, and machine operators (type unspecified). Among male cases, electricians were significantly overrepresented (5% level). Jobs for which there was a suggestion (p < 0.1) of overrepresentation among cases included butchers and teacher/lecturers (both males only) and the combined job groups (chosen a priori for analysis) of keyboard operators, machine operators, and music teachers (all three jobs, females only).

Adolescent

[Reactivity of cortical bone capillaries. Functional TEM analysis with adrenaline, ATP and insulin].

In order to study any morphological effects that vasoactive drugs might exert on cortical bone capillaries, Swiss mice received one intravenous bolus injection each of epinephrine, ATP and insulin. In one control group saline solution was injected and another was not treated. All animals were handled in the same way. A piece of the tibia diaphysis was resected and prepared for transmission electron microscopy (TEM). The lumina and the endothelia of capillaries were submitted to computerized morphometry. Some significant changes were noted: epinephrine increases both the width of the lumen and the endothelium. ATP decreases the endothelium. Insulin (hypoglycaemia?) thickens the endothelium. These finding suggest some physiological hypotheses: the epinephrine-induced widening of the lumen and the thickening of the endothelium might reflect a decreased extravasal space and oedema of cortical bone that might cause the diffusion of minerals to take longer. Intracortical perfusion pressure would then decrease and the bone perfusion rate increase. ATP might reduce the transcapillary diffusion time and increase the extravasal space in cortical bone. Apparently there are specific insulin receptors in cortical bone capillaries.

Adenosine Triphosphate

The design and performance of an experimental external fixation device with load transducers.

It is becoming increasingly common that fracture healing is modelled in the laboratory with an osteotomy in the diaphysis of the ovine tibia. External fixation is often used to hold the bones in these models, presenting the problem that the loads on such devices are poorly understood. To help investigate this, a unilateral device has been developed which is capable of measuring the two components of load considered to be the most important, that of axial compression and bending in the plane of the fixator. The device was found to be a rigid system and easy to apply, with the in-vivo measurements being straightforward. The estimated limits of error of the compression transducer are +37.9 N and -21.4 N and those of the bending transducer are +3.6 Nm and -4.2 Nm. Preliminary measurements showed the maximum load during normal walking to 345 N compression and 28 Nm in-plane bending.

Animals

Measurement of serum angiogenic factor in devascularized experimental tibial fractures.

Early recovery of the vasculature is of profound importance in healing fractures, but the exact role of the regenerating endothelium remains controversial. Serum activity of endothelial cell-stimulating angiogenesis factor (ESAF) was measured after tibial osteotomy in two groups of sheep over a period of 42 days. Each osteotomy was held in an instrumented external fixator, and in one group the musculoperiosteal vasculature was excluded from the osteotomy site. In the well-vascularized group (n = 4), ESAF activity was significantly higher 2-5 days after osteotomy, with a peak at 4 days (21.1 +/- 5.4, p < 0.05), and displayed a biphasic pattern of secretion with a second peak at 7 days (24.3 +/- 5.5). In the devascularized group (n = 4) overall activity was lower, with only a single peak occurring at 9 days (17.5 +/- 3.2). These findings were correlated with significant differences in structural properties and on histological examination. The early detection of such regional vascular responses may prove to be of significant clinical value in high-energy trauma, enabling prediction of those fractures at risk of delayed or nonunion.

Angiogenesis Inducing Agents

A new in-vitro model to investigate antibiotic penetration of the intervertebral disc.

We have studied the ability of a range of antibiotics to penetrate intervertebral disc tissue in vitro, using a mouse disc model. Equilibrium concentrations of antibiotics incorporated into the entire disc were determined by bioassay using a microbial growth-inhibition method. Uptake was significantly higher with positively-charged aminoglycosides compared with negatively-charged penicillins and cephalosporins. Uncharged ciprofloxacin showed an intermediate degree of uptake. Our results support the hypothesis that electrostatic interaction between charged antibiotics and negatively-charged glycosaminoglycans in the disc is an important factor in antibiotic penetration, and may explain their differential uptake.

Animals

The acute vascular response to intramedullary reaming. Microsphere estimation of blood flow in the intact ovine tibia.

The tibial nutrient artery supplies 62% of cortical blood flow in the diaphysis and normal blood flow is centrifugal (Willans 1987). Intramedullary reaming destroys the nutrient artery and injures the endosteal surface of the cortex. Trueta (1974) suggested that the direction of blood flow can reverse from centrifugal to centripetal after loss of the endosteal supply. We examined this hypothesis by measuring cortical and periosteal blood flow after intramedullary reaming of the tibia in eight sheep, using 57Co radiolabelled microspheres. The unreamed contralateral tibiae served as a control group. Thirty minutes after reaming there was no significant change in cortical blood flow, but a sixfold increase in the periosteal flow. Our study confirms Trueta's hypothesis; after trauma or in other pathological states, flow can become centripetal.

Animals

Cervical spine fractures.

A classification of cervical spine injuries based upon Dunn's concept of stable and unstable fractures is presented. The role of conservative treatment using Halo-body fixation is outlined along with the various approaches to the cervical spine and their method of ensuring stability.

Cervical Vertebrae

Humoral regulation of blood flow in the vertebral endplate.

STUDY DESIGN: Blood flow in the sheep lumbar spine was measured. OBJECTIVES: The effect of vasoactive agents, noradrenaline and acetylcholine, on blood flow adjacent to the disc--bone interface was determined. SUMMARY OF BACKGROUND DATA: The main route for disc nutrition is through the vertebral endplate. Although the vascular anatomy in this region has been well described, its response to neurohumoral influences has not been quantified. METHODS: Blood flow in bone adjacent to the lumbar intervertebral discs was measured using the microsphere technique before and after infusions of noradrenaline and acetylcholine in two groups of five female sheep. Systemic arterial pressure was measured during each infusion. RESULTS: Vertebral bone blood flow was unchanged during noradrenaline infusion, but increased by 60% during acetylcholine infusion. This was associated with a significant decrease in systemic arterial pressure. CONCLUSIONS: These data are consistent with the existence of muscarinic receptors in vessels of the vertebral endplate, which suggests that the vasculature may influence disc nutrition.

Acetylcholine

The vascular response to fracture micromovement.

Micromovement has been shown to promote the healing of experimental fractures, but its role in the clinical management of fractures with soft-tissue injury is less certain. In a 2-mm transverse osteotomy of the ovine tibia held in an instrumented external fixator, axial interfragmentary displacement was quantified in vivo for six weeks after osteotomy. Group I (n = 11) had an axial fixation stiffness of 460 N/mm and Group II (n = 12) had a stiffness of 238 N/mm. With a 25% difference in micromovement, a fourfold change in corticomedullary blood flow was observed at two weeks after osteotomy (p < 0.01). Although by six weeks mechanical properties in torsion were similar, there were marked differences in the periosteal cross-sectional perimeter, area, and intracortical porosity that complemented the hemodynamic changes. The early vascular response is very sensitive to the initial mechanical environment, and appears to precede and determine the organization of osteogenesis. Further understanding of this relationship may prove to be of direct clinical relevance in the augmentation of healing of devascularized diaphyseal fractures.

Animals

Quantitative early phase scintigraphy in the prediction of healing of tibial fractures.

Imaging with technetium-99m methylene diphosphonate (99mTc-MDP) is established in the diagnosis of infection, neoplasia and ischaemic necrosis in orthopaedic practice, but its role in fracture healing is less well-defined. Previous studies have shown a relationship between fracture site activity (region A), activity in adjacent normal bone (region C) and time to union. The predictive value of the A/C ratio of the image obtained 300-800 s after injection was assessed in a prospective study of 50 patients with closed tibial fractures managed with plaster casts, external fixators and intramedullary nails. There were significant differences in absolute uptake and A/C ratio between the three groups (P less than 0.05), but this was not related to time to union. Reamed nailing alters the distribution of 99m-Tc-MDP uptake so as to reduce the A/C ratio (1.10 +/- 0.20), but there is a promising role for early phase bone scanning in non-operative (A/C = 1.40 +/- 0.21) or externally fixed (A/C = 1.26 +/- 0.22) fractures in conjunction with other non-invasive methods of monitoring the biomechanical environment.

Adolescent