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Biomedical subjects

S P Hughes

Publications and source records attributed to S P Hughes.

At least 19 recordsLinked to original sources

Global spinal motion in subjects with lumbar spondylolysis and spondylolisthesis: does the grade or type of slip affect global spinal motion?

STUDY DESIGN: This was a prospective pilot study to investigate the global motion characteristics of the spondylolysis and spondylolisthesis populations. OBJECTIVES: The aim of this study is to determine the influence of a spondylolisthesis or a spondylolysis on global spinal motion and to establish whether this is dependent on the cause of the slip or the degree/grade of the slip. SUMMARY OF BACKGROUND DATA: The condition of spondylolisthesis has been extensively discussed in the literature with respect to its etiology and management. However, the mechanics and movement of the spine in relation to pathology and the effect of this condition on function have received scant attention. METHODS: The motion of the lumbar spine was investigated in 31 patients (19 men, 12 women, mean age 47.7 +/- 17.8 years) who were diagnosed as having either a lumbar spondylolysis or a spondylolisthesis. These patients were compared with a preexisting database of 203 normal subjects (100 men, 103 women, mean age 39.8 +/- 13.4 years). Patients were graded according to the type of spondylolisthesis or spondylolysis they had, and the extent of slip was rated using Meyerding's classification (1932) and measured directly using methods of Boxall et al (1979) and Wiltse et al (1983). RESULTS: Direct measurements of the extent of slip using Boxall et al (1979) and Wiltse et al (1983) methods were found to have no significant correlation with the resultant range of motion (ROM) or the speed of movement. This study suggests that motion parameters are influenced by the grade of slip in patients with spondylolisthesis, and the type of spondylolisthesis i.e., whether isthmic or degenerative. In the A-P flexion-extension plane, the results indicate that subjects with a defect only, i.e., a spondylolysis, and thus no slip present with a spinal hypermobility (P < 0.01). Subjects with an isthmic slip tend to be either slightly hypermobile or within the anticipated range of motion, whereas those subjects with a degenerative slip tend to be hypomobile (P < 0.05). Movements into lateral flexion were restricted in both the isthmic and degenerative spondylolisthesis patients, whereas rotation was only influenced by the level at which the defect occurred. In terms of degree of displacement, in higher grades of displacement, there was a trend towards hypermobility. CONCLUSIONS: The findings of this study suggest that the grade and type of spondylolisthesis do influence global motion parameters. This information may be useful in the clinical assessment of this patient group.

Adult↗

Investigation of vertebral "end plate sclerosis".

OBJECTIVE: To evaluate the association between vertebral "end plate sclerosis" and neck pain. DESIGN: A retrospective study was carried out of lateral cervical spine radiographs with a Picture Archive and Communication System (PACS). PATIENTS: Two hundred patients' files were randomly assessed, comprising four equal groups, A to D. The mean ages of the patients were 62+/-7.4 years, 61+/-7.5 years, 40+/-5.6 years and 23+/-5.6 years respectively. In group A, all patients had symptoms of neck pain and a radiographic diagnosis of "end plate sclerosis" of the cervical spine. In groups B to D, asymptomatic patients were recruited and their age groups were 50-69, 30-49 and 10-29 years respectively. Using the PACS, the radiographic density and the sagittal diameter, thickness and area of the end plates at the C5 level were measured. RESULTS AND CONCLUSIONS: No significant differences were found in the radiographic density of the end plates either between the symptomatic and asymptomatic groups (groups A and B), or between different age groups (groups B, C and D). A significant increase in end plate area and thickness was found, however, in both group B (P<0.005) and group C (P<0.01) in comparison with group D. This indicates that the extent of end plate sclerosis increases with age. Our results suggest that the radiographic density of cervical vertebral end plates correlates neither with neck pain nor with increasing age. The radiological sign of "end plate sclerosis" may be over-reported, further limiting its value in the assessment of patients with cervical spondylosis.

Adolescent↗

The influence of initial resting posture on range of motion of the lumbar spine.

The aim of this study was to investigate the influence of initial resting posture on range of motion of the lumbar spine in 18 normal subjects. Subjects resting posture and active range of motion was measured using the CA-6000 Spinal Motion Analyser (OSI, USA) in five test positions, namely in flat standing and with a variety of heel raises. Analysis showed that there was no significant correlation between subject's normal resting posture and active range of motion. However, when subjects resting posture was artificially altered with heel raises, significant effects on the active range of motion were demonstrated. Increasing heel height significantly influenced resting posture in the sagittal plane only. As heel height increased, the lumbar lordosis decreased and a significant reduction in the range of lumbar spine flexion (P<0.001) was observed. Simulating pelvic asymmetry influenced resting posture in the frontal plane and significant effects on the range of lateral flexion (P<0.05) were observed. These results have important clinical implications in terms of using range of motion of the lumbar spine as an examination tool and suggest that studies using range of motion as an outcome measure should consider initial resting posture.

Adult↗

Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells.

Pluripotent embryonic stem (ES) cells have the potential to differentiate to all fetal and adult cell types and might represent a useful cell source for tissue engineering and repair. Here we show that differentiation of ES cells toward the osteoblast lineage can be enhanced by supplementing serum-containing media with ascorbic acid, beta-glycerophosphate, and/or dexamethasone/retinoic acid or by co-culture with fetal murine osteoblasts. ES cell differentiation into osteoblasts was characterized by the formation of discrete mineralized bone nodules that consisted of 50-100 cells within an extracellular matrix of collagen-1 and osteocalcin. Dexamethasone in combination with ascorbic acid and beta-glycerophosphate induced the greatest number of bone nodules and was dependent on time of stimulation with a sevenfold increase when added to ES cultures after, but not before, 14 days. Co-culture with fetal osteoblasts also provided a potent stimulus for osteogenic differentiation inducing a fivefold increase in nodule number relative to ES cells cultured alone. These data demonstrate the application of a quantitative assay for the derivation of osteoblast lineage progenitors from pluripotent ES cells. This could be applied to obtain purified osteoblasts to analyze mechanisms of osteogenesis and for use of ES cells in skeletal tissue repair.

Animals↗

Assessment of spinal kinematics using open interventional magnetic resonance imaging.

Assessment of spinal intersegmental motion has been a focus for research and has depended on radiographic techniques. Radiographic techniques are limited because of ionizing radiation exposure, magnification errors, and image quality. Interventional magnetic resonance scanners, however, allow dynamic imaging in the scanner in different positions. Twelve healthy subjects were scanned using a General Electric Signa SP10 open interventional magnetic resonance scanner. Subjects were scanned while they were in the supine position and during sitting in flexed and extended positions. Measurements of lumbar curvature and intersegmental motion were made from the sagittal images obtained. The results showed that it was possible to obtain repeatable measures of intersegmental rotation and translation from open magnetic resonance images of the spine in flexed and extended positions. These measures of motion are in agreement with previous data and suggest that the greatest motion occurs at the L4-L5 level. The use of interventional magnetic resonance imaging for assessing lumbar intersegmental mobility seems promising.

Adult↗

Geometrical dimensions of the lower lumbar vertebrae--analysis of data from digitised CT images.

The precise dimensions of the lumbar vertebrae and discs are critical for the production of appropriate spinal implants. Unfortunately, existing databases of vertebral and intervertebral dimensions are limited either in accuracy, study population or parameters recorded. The objective of this study is to provide a large and accurate database of lumbar spinal characteristics from 126 digitised computed tomographic (CT) images, reviewed using the Picture Archiving Communication System (PACS) coupled with its internal measuring instrumentation. These CT images were obtained from patients with low back pain attending the spinal clinic at the Hammersmith Hospitals NHS Trust. Measurements of various aspects of vertebral dimensions and geometry were recorded, including vertebral and intervertebral disc height. The results from this study indicated that the depth and width of the vertebral endplate increased from the third to the fifth lumbar vertebra. Anterior vertebral height remained the same from the third to the fifth vertebra, but the posterior vertebral height decreased. Mean disc height in the lower lumbar segments was 11.6 +/- 1.8 mm for the L3/4 disc, 11.3 +/- 2.1 mm for the L4/5, and 10.7 +/- 2.1 mm for the L5/S1 level. The average circumference of the lower endplate of the fourth lumbar vertebra was 141 mm and the average surface area was 1,492 mm2. An increasing pedicle width from a mean of 9.6 +/- 2.2 mm at L3 through to 16.2 +/- 2.8 mm at L5 was noted. A comprehensive database of vertebral and intervertebral dimensions was generated from 378 lumbar vertebrae from 126 patients measured with a precise digital technique. These results are invaluable in establishing an anthropometric model of the human lumbar spine, and provide useful data for anatomical research. In addition this is important information for the scientific planning of spinal surgery and for the design of spinal implants.

Adult↗

SPECT in the management of patients with back pain and spondylolysis.

PURPOSE: Single photon emission computed tomography (SPECT) bone scans of the lumbar spine were evaluated in the management of patients with low back pain and suspected spondylolysis. MATERIALS AND METHODS: Thirty-three patients (mean age, 30 years) with high clinical suspicion of pars interarticularis defects were included in the study. The results of lumbar radiographs and SPECT bone scintigraphy were compared and the influence of these results on patient management was evaluated. RESULTS: Twenty-six of the 33 patients had abnormal results of lumbar radiographs. Of the 21 patients with radiographs indicating spondylolysis, six had abnormal uptake in the pars regions on bone scintigraphy. One patient with normal results of lumbar radiographs had a SPECT bone scan showing uptake in the region of the pars interarticularis. CONCLUSIONS: SPECT bone scanning of the lumbar spine has a role in the treatment of patients with symptomatic spondylolysis.

Adult↗

Nitric oxide mediated vasoreactivity during fracture repair.

An experimental model of fracture healing has been used to investigate whether nitric oxide mediated vascular reactivity, determined using laser Doppler flowmetry, is present in bone after a fracture. Times corresponding to Days 0, 1, 3, 7, 14, and 28 after fracture were used to study the injured and contralateral limbs in response to bolus intravenous administration of nitric oxide inhibitor, N-nitro-L-arginine methyl ester, and nitric oxide stimulator, acetylcholine. N-nitro-L-arginine methyl ester administration (1 mumol/kg, 10 mumol/kg, and 100 mumol/kg) caused a dose dependent increase in systemic blood pressure in each of the assessment groups; however, there was no statistical difference between the groups. Doppler flow readings at the fracture site showed measurable changes in local vascular reactivity after drug administration. At Day 1 after fracture, the magnitude of unit change in vascular reactivity in response to N-nitro-L-arginine methyl ester (1 mumol/kg, 10 mumol/kg, and 100 mumol/kg) was significantly higher in the fractured limb compared with the contralateral limb and also when compared with other points of assessment. These results show that nitric oxide mediated vasoreactivity is present about a fracture site and is maximal in the early healing phase, before returning to basal levels as healing progresses. This is compatible with an initial restoration of blood flow at a fracture site by nitric oxide dependent vasodilation of preexisting blood vessels, followed by ingrowth of less nitric oxide dependent angiogenic vessels during the later phase of repair.

Acetylcholine↗

Nitric oxide in fracture repair. Differential localisation, expression and activity of nitric oxide synthases.

Our aim was to investigate whether nitric oxide synthase (NOS) isoforms, responsible for the generation of NO, are expressed during the healing of fractures. To localise the sites of expression compared with those in normal bone we made standardised, stabilised, unilateral tibial fractures in male Wistar rats. Immunostaining was used to determine the precise tissue localisation of the different NOS isoforms. Western blotting was used to assess expression of NOS isoform protein and L-citrulline assays for studies on NOS activity. Control tissue was obtained from both the contralateral uninjured limb and limbs of normal rats. Immunohistochemistry showed increased expression of endothelial NOS (eNOS) to be strongest in the cortical blood vessels and in osteocytes in the early phase of fracture repair. Western blot and image analysis confirmed this initial increase. Significantly elevated calcium-dependent NOS activity was observed at day 1 after fracture. Inducible NOS (iNOS) was localised principally in endosteal osteoblasts and was also seen in chondroblasts especially in the second week of fracture healing. Western blotting showed a reduction in iNOS during the early healing period. Significantly reduced calcium-independent NOS activity was also seen. No neuronal NOS was seen in either fracture or normal tissue. Increased eNOS in bone blood vessels is likely to mediate the increased blood flow recognised during fracture healing. eNOS expression in osteocytes may occur in response to changes in either mechanical or local fluid shear stress. The finding that eNOS is increased and iNOS reduced in early healing of fractures may be important in their successful repair.

Animals↗

Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion and the acute-phase response in patients with bacterial and tuberculous osteomyelitis.

Osteomyelitis, or bone infection, is a major worldwide cause of morbidity. Treatment is frequently unsatisfactory, yet little is known about pathogenesis of infection. Plasma tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 concentrations were measured before and after lipopolysaccharide stimulation of whole blood from patients with bacterial and tuberculous osteomyelitis and from controls. Patients with bacterial and tuberculous osteomyelitis mounted an acute-phase response and were anemic and febrile. However, plasma IL-6 concentrations were significantly elevated in only tuberculous osteomyelitis patients (vs. controls, P < .05). IL-6 concentrations correlated with erythrocyte sedimentation rate, C-reactive protein level, and plasma albumin concentration, all acute-phase markers. There were no other correlations between cytokine concentrations and clinical data. Following ex vivo stimulation, TNF, IL-6, and IL-8 were secreted equally by patients and controls. In summary, tuberculous osteomyelitis is characterized by elevated systemic IL-6 concentrations associated with an acute-phase response. For further insight into immunopathology of osteomyelitis, studies on infected bone are required.

Acute-Phase Reaction↗

Spinal motion in lumbar degenerative disc disease.

We have measured the dynamic movement of the lumbar spine in 57 patients with degenerative lumbar disc disease. Each completed a questionnaire which recorded pain and subjective signs and symptoms. From plain lateral radiographs, the subjects were graded using the criteria of Kellgren and Lawrence and those of Lane et al, which are both based on the severity of degenerative changes. Measurements of the height of the disc space and the vertebral height were obtained and expressed as a ratio. We found no relationship between the characteristics of spinal movement and the overall grading of degenerative disc disease with either system. Both were influenced (p < 0.01) by age, walking distance, severity of symptoms, drug intake and frequency of pain. The present systems for grading degenerative disc disease from plain lateral radiographs have limited application.

Female↗

Are subjective clinical findings and objective clinical tests related to the motion characteristics of low back pain subjects?

Many authors have demonstrated that low back pain sufferers have impaired spinal motion. However, it is not known to what degree the patient's signs and symptoms influence this impairment in motion. The aim of this study was therefore to conduct an explorative study to investigate the relationship between low back pain patients' signs and presenting symptoms and objective measurements of motion. One hundred thirty-eight patients with low back pain completed a questionnaire detailing their signs and symptoms and underwent a full clinical examination. A potentiometric motion analysis system of known accuracy and repeatability was used to measure their spinal motion during a flexion-extension test. The effects of a variety of subjective and clinical findings on the motion characteristics were examined, which revealed that certain factors, such as diagnosis, pain characteristics, symptom severity, and level of disruption, were related to the resulting motion measurements. The strength of these relationships were not as strong as anticipated (accounting for 16-45% of the variability). This suggests that routine objective assessments cannot be used as a substitute for a thorough physical and subjective examination.

Activities of Daily Living↗

Nitric oxide in the local host reaction to total hip replacement.

Nitric oxide is emerging as one of the most studied molecules in many aspects of human physiology and pathophysiology. Because of the inflammatory nature of aseptic loosening of total hip replacement, it is likely that nitric oxide plays a major role in this condition as well. Nitric oxide is known to interact with cyclooxygenase enzymes that produce prostanoids. Nitric oxide can stimulate synthesis and activity of the inducible, proinflammatory isoform of the enzyme, namely, cyclooxygenase 2. Interactions between the cytokine inducible nitric oxide synthase and cyclooxygenase 2 pathways serve to regulate bone cell viability such that cyclooxygenase 2 activity can protect against nitric oxide mediated programmed cell death. In the pseudomembrane these two pathways are coactivated in CD68 positive macrophages, fibroblasts, lining cells, and in vascular smooth muscles. Particle generation from wear of the prosthesis has a significant role as an inducer of nitric oxide synthase and cyclooxygenase 2; macrophages laden with small size particles and positive for inducible nitric oxide synthase and cyclooxygenase 2 are a frequent finding. Nitric oxide readily reacts with superoxide to form peroxynitrite, which is a strong oxidant species. In pseudosynovial interface membrane, detection of nitrotyrosine provides evidence for the formation and activity of peroxynitrite. These findings show evidence that nitric oxide, superoxide, and peroxynitrite mediated cellular damage is part of the pathophysiology of aseptic loosening of joint implants. These new findings suggest that antiinflammatory compounds can be useful to treat early aseptic loosening of joint implants.

Animals↗

Initial assessment of back pain: an overview.

In any illness, the severity of symptoms and their effect on lifestyle are very important to the patient. Pain in the back may indicate simple backache which most people have at some time, a number of serious spinal diseases or low back disability. It is important to establish to which category a patient belongs, and this article will outline some of the methods by which this can be achieved.

Back Pain↗

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↗

The design and performance of an experimental external fixator with variable axial stiffness and a compressive force transducer.

A unilateral external fixator has been designed for controlled experiments into the effects of micromovement on fracture healing. The experimental model used is based on a diaphyseal osteotomy of the right tibia of the sheep. The main bar has linear bearings, which allows free axial movement. This is then controlled by a spring whose stiffness can be varied. The resulting axial micromovement can be calculated from the measured compressive force and the known axial stiffness of the fixator. The transducer has limits of error of +13.3 N and -44.5 N. Preliminary measurements showed maximum micromovement at the fracture site of 0.48 mm during slow walking.

Animals↗