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.
IntroductionAccurate and comprehensive anthropometric data for the lumbar spine vertebrae, a frequent site for implantation surgery, are incomplete at present. Information on the precise dimensions of the lower lumbar vertebrae is, however, essential, for the rational design and development of spinal implants and instrumentation such as pedicle screws and, in particular, with the evolution towards robotic surgery. Previous studies have depended on direct measurements from plain X-ray films [9,12,13,23], or from computed tomographic (CT) scans [8,11,26,34,36]. A few reports have involved the analysis of cadaveric specimens [1,7,24,27,29]. The value of the data has depended on the number of samples and the accuracy of Abstract 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 1492 mm 2 . 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.
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.
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.
We examined the effect of periosteal devascularisation upon the early healing of osteotomies of sheep tibiae held in an instrumented external fixation system with an axial stiffness of 240 N/mm. At 14 days, cortical blood flow measured by the microsphere technique was 19.3 ml/min/100g in the well-vascularised osteotomies, but only 1.7 ml/min/100g in the devascularised osteotomies, despite an increase in medullary flow (p less than 0.0005). Delay in healing of the devascularised osteotomies was suggested by an in vivo monitoring system and confirmed by post-mortem mechanical testing. We suggest that the osteogenic stimulus of dynamic external fixation is dependent on the early restoration of cortical blood flow in devascularised fractures.
There has been a long-standing debate as to whether medullary or periosteal flow is the dominant vascular supply during the healing of diaphyseal fractures. We used radioactive microspheres to quantify blood flow to the canine tibia two weeks after an osteotomy. There was a significant contribution from the periosteum to the blood supply of healing cortical bone after nutrient artery ligation, with a reversal of flow from a centrifugal to a centripetal direction. Our study has confirmed the qualitative observations of Trueta (1974) regarding the significant recruitment of vessels from surrounding soft tissue during fracture healing. We have not studied the later stages of healing.
In order to evaluate the reliability of anthropometry in assessing protein stores we have compared, in 10 normal adults and 82 surgical patients with varying degrees of weight loss, measurements of weight/height, arm circumference, arm muscle circumference, and arm muscle area with direct measurements of body nitrogen using in vivo neutron activation analysis. Anthropometry is reliable for the assessment of protein nutrition in groups of patients (for 100 patients 95% confidence limits are +/- 30 g nitrogen) but the magnitude of variance shown makes it inappropriate for assessing the individual as a single measurement (95% confidence limits are +/- 300 g nitrogen). Repeat measurements were made after 2 weeks on 35 patients and there was no correlation between changes in body nitrogen and changes in the anthropometric measurements. Anthropometry is not reliable in following changes in body nitrogen in individual patients over short periods of time.
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