Rib-vertebral angle asymmetry in idiopathic, neuromuscular and experimentally induced scoliosis.

The concave and convex rib-vertebral angle (RVA) at levels T2-T12 was measured on AP radiographs of 19 patients with right convex idiopathic thoracic scoliosis and 10 patients with major thoracic right convex neuromuscular scoliosis. The difference between the angles on the concave and the convex sides, the RVAD, was calculated. The RVAs were also measured on radiographs from three animal groups in which spinal curves had been induced experimentally in a variety of ways. Group 1 comprised 16 rabbits that had been subjected to selective electrostimulation of the latissimus dorsi, the erector spinae and the intercostal muscles. Group 2 comprised four dead rabbits whose spines had been subjected to manual bending. Group 3 comprised eight rabbits that had undergone mechanical elongation of one rib. In both the idiopathic and the neuromuscular group, the convex RVA was smaller than the concave RVA between levels T2 and T8, with a maximal difference between T4 to T5. From T9 to T12 the concave RVA was smaller than the convex. The RVA in relation to the scoliotic segment, i.e. the apex level of the curve and the two neighbouring vertebrae above and below this level, showed similar results. With increasing Cobb angle the RVADs increased linearly with the greatest difference at the second vertebra above the apex. In the three experimental groups the pattern of the RVADs between T6 to T12 was basically similar to the findings of the clinical study. From the results of these clinical and experimental studies, it is concluded that the typical pattern of the RVAs on the concave and convex sides seems to be independent of the underlying cause of the spinal curvature. It is likely that the RVADs result from a passive mechanical adaptation of the ribs to the lateral curvature of the spine.

The position of the aorta in relation to the vertebra in patients with idiopathic thoracic scoliosis.

One CT-scan at the central part of the vertebral body of the apical vertebra of 32 patients with right convex thoracic idiopathic scoliosis and one CT-scan of either T8 or T9 of 22 normal subjects are included in this study. The position of the aorta in relation to the apical vertebra of the scoliotic patients and the corresponding vertebra of the normal subjects was determined at the horizontal plane. The mean lateral translation of the aorta in relation to the mid axis of the vertebral body increased from 19.7 +/- 4.3 mm in the normal group to 26.4 +/- 4.1 mm in the scoliotic group (p = 0.0001). In the normal group the aorta was located 41.7 +/- 8.6 mm in front of a perpendicular line to the mid axis of the vertebral body and in the scoliotic group this distance was reduced to 30.0 +/- 9.0 mm making the position of the aorta more posterior in the scoliotic group (p = 0.0001). This was in accordance with a decreased mean kyphosis-lordosis index from 0.53 +/- 0.06 in the normal group to 0.46 +/- 0.07 in the scoliotic group (p = 0.01). The position of the aorta, also expressed as the angle formed between the aorta and the vertebral body, the "aorto-vertebral angle", was increased from 24.4 degrees +/- 6.9 degrees in the normal group to 41.4 degrees +/- 8.4 degrees the scoliotic patients, (p = 0.0001). The aorto-vertebral angle did not change significantly with increasing Cobb angle (p = 0.26) but was positively correlated to the vertebral rotation (p = 0.0001). An estimation of the length of the intercostal arteries revealed a significantly greater R (right)/L (left) index in the scoliotic patients 1.18 +/- 0.11 than in the normal subjects 1.08 +/- 0.06 (p = 0.0003). It is concluded that the rotation and the anterior displacement of the vertebral body in scoliosis result in a deviation of the aorta along the left (concave) side of the vertebral body to a more posterior position relative to the vertebral body with a possible increased length of the intercostal artery on the right (convex) side.

Electrical muscle stimulation on the spine. Three-dimensional effects in rabbits.

We investigated the 3-dimensional effect of electrostimulation of the latissimus dorsi, the erector spinae and the intercostal muscles on spinal configuration in 16 New Zealand white rabbits. Electrostimulation on the right side of the spine resulted in a left convex, hypokyphotic curve and vertebral body rotation towards the convexity of the curve in all rabbits. The Cobb angle in the coronal plane increased with stimulation of each of the muscles examined. The kyphosis decreased with stimulation of the latissimus dorsi and the erector spinae. The vertebral rotation increased with stimulation of all muscles. Stimulation of the tested muscles resulted in the simultaneous occurrence of a 3-dimensional spinal deformity with the characteristics of idiopathic scoliosis.

In vitro opto-electronic analysis of 3-D segmental vertebral movements during gradual rib lengthening in the pig.

The effects of gradual rib elongation on the 3-D position of neighboring vertebrae were studied in vitro in two pig specimens. The ends of one osteotomized rib were gradually distracted and the micromovements of the numerically corresponding vertebra with the osteotomized rib were studied in relation to the subjacent and suprajacent vertebrae with an opto-electronic motion analysis device. The study showed that gradual lengthening of the rib resulted in micromovements of the central vertebra in relation to the neighboring vertebrae registered as a) lateral translation in the coronal plane, b) rotation in the horizontal plane (both a and b were movements towards the opposite side of the lengthened rib), c) ventral translation in the sagittal plane and d) tilt in the coronal and sagittal planes. All movements were registered simultaneously. There was a significant linear correlation with the degree of rib elongation. From the results of this study it is concluded that gradual elongation of one rib affects the position of the numerically corresponding vertebra in relation to the suprajacent and subjacent vertebrae in the three cardinal planes in the same way as the apex vertebra is affected in idiopathic scoliosis. Moreover, the registered tilt, i.e., the rotational movement of the central vertebra in the coronal plane, could explain the wedging of the disc space, and the ventral translation in combination with the tilt in the sagittal plane could account for the lordotic tendency of the scoliotic segment.

Structural vertebral changes in the horizontal plane in idiopathic scoliosis and the long-term corrective effect of spine instrumentation.

The rotation and structural changes of the apex vertebra in the horizontal plane as well as of the thoracic cage deformity were quantified by measurements on computed tomography (CT) scans from patients with right convex thoracic idiopathic scoliosis (IS). The CT scans were obtained from 12 patients with moderate scoliosis (mean Cobb angle 25.8 degrees, r 13 degrees-30 degrees) and from 33 with severe scoliosis (mean Cobb angle 46.2 degrees, r 35 degrees-71 degrees). In addition, CT scans of thoracic vertebrae from 15 patients without scoliosis were used as reference material. Ten of the scoliotic cases had had Cotrel-Dubousset instrumentation (CDI) and posterior fusion and had entered a longitudinal study on the effect of operative correction on the re-modelling of the apical vertebra. An increasingly asymmetrical vertebral body, transverse process angle, pedicle width and canal width were found in the groups with scoliosis as compared with the reference material. Vertebral rotation and rib hump index were significantly larger in patients with early and advanced scoliosis than in normal subjects. The modelling angle of the vertebral body, the transverse process angle index and the vertebral rotation in relation to the middle axis of the thoracic cage were significantly greater in patients with severe than with moderate scoliosis. The results of this longitudinal study suggest that the structural changes of the apical vertebra regress 2 years or more after CD instrumentation.

Horizontal plane morphometry of normal and scoliotic vertebrae. A methodological study.

Computed tomography (CT) scans are widely used for quantification of the morphology of the vertebral body and of the changes of the thoracic cage in the horizontal plane in scoliosis. So far, however, no method exists for precise quantification of the parameters of the posterior elements. We present a method for quantification on the basis of CT scans of different parameters of the morphology of both the vertebral body and posterior elements in the horizontal plane. The precision and accuracy of the method were estimated in a model study by CT scanning of a normal and a scoliotic vertebra in different, controlled, tilted positions. Moreover, in a clinical study CT scans of 19 thoracic vertebrae from non-scoliotic subjects and the apex vertebra from 40 scoliotic subjects were selected to test the applicability of the method to clinical studies. The intra- and interobserver variation of the measurements was analysed. The angle between the longitudinal axis of the vertebral body and that of the whole vertebra was used to evaluate the asymmetry of the vertebral body. The right to left pedicle width index, the right to left hemi-canal width index and the index of transverse process angles related to the axis of the vertebra were used to quantify the asymmetry of the posterior elements. The results indicate that, except for the pedicle width index, the variables under study were not significantly influenced by a 5 degrees or 10 degrees tilt ventrally, dorsally, or laterally of either the normal or the scoliotic vertebra. Hence, the method can be satisfactorily applied to longitudinal group comparisons.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertebral rotation and pedicle length asymmetry in the normal adult spine.

Rotation in the horizontal plane of vertebra T8, T9 or T10 was determined on CT scans of 25 male and 25 female patients with normal spines. The pedicle length was measured using a new method, and the right/left pedicle length index was calculated. In 38 (76%) of the patients there was vertebral rotation to the right with a mean Cobb angle of 3.0 degrees, and in 4 (8%) rotation to the left, mean Cobb angle 2.2 degrees (P < 0.01). In 8 (16%) there was no measurable rotation. The pedicle length index was greater than 1.05 in 9 subjects, between 0.95 and 1.05 in 16 and less than 0.95 in 25, indicating a predominance of longer pedicles on the left side. In 21 out of the 38 patients with vertebral rotation to the right, the left pedicle was longer than the right one (P < 0.01). The results indicate that the normal spine is afflicted with a vertebral rotation to the right in association with a longer pedicle on the left. The significance of these observations for the pathogenesis of idiopathic scoliosis remain uncertain.

Atherosclerosis and sterol 27-hydroxylase: evidence for a role of this enzyme in elimination of cholesterol from human macrophages.

27-Hydroxycholesterol was found in surprisingly high amounts in atherosclerotic human femoral arteries. When human macrophages were cultured in a medium containing serum, there was a significant transfer of 27-hydroxy-cholesterol and 3 beta-hydroxy-5-cholestenoic acid from the cells into the medium. Sterol 27-hydroxylase (EC 1.14.13.15) is likely to be responsible for formation of the two products as shown by use of immunoblotting, a specific inhibitor, and the 18O-labeling technique. Sterol 27-hydroxylase has the unusual ability to hydroxylate the same methyl group three times to give a carboxylic acid; thus, 3 beta-hydroxy-5-cholestenoic acid is likely to be a direct product of the enzyme. The production of these steroids increased after addition of cholesterol to the culture medium. By using deuterium-labeled cholesterol, it was ascertained that most of the oxidized products were formed from exogenous cholesterol taken up by the cells. 27-Hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid are present in the circulation and are efficiently converted into bile acids in human liver. It is suggested that conversion of cholesterol into 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid represents a general defence mechanism for macrophages and possibly also other peripheral cells exposed to cholesterol. Absence of this defence mechanism may contribute to the premature atherosclerosis known to occur in patients with sterol 27-hydroxylase deficiency (cerebrotendinous xanthomatosis).

Sagittal configuration of the spine and growth of the posterior elements in early scoliosis.

The early changes of the sagittal alignment of the spine and the asymmetry between the posterior and anterior elements were determined on the basis of 134 lateral and 167 anteroposterior radiographs obtained from a control group and from patients with early scoliosis. The radiographs were allocated into four groups according to the degree of the Cobb angle. In thoracic curves with a Cobb angle of more than 8 degrees, the kyphosis and the vertebral sagittal wedge angle decreased in comparison with the control group. The sagittal-wedge angle of the disc did not change significantly with increasing Cobb angle. The pedicle height in relation to the vertebral height, considered to represent the growth of the posterior element in relation to the growth of the anterior element, was not significantly different in the scoliotic groups as compared with the control group. The results indicate that changes of the sagittal configuration of the spine occur early in idiopathic scoliosis and that they are associated with disturbed growth of the vertebral body but not of the posterior elements. These findings seem to reflect a simultaneous deformation in the coronal and sagittal planes rather than a single growth disturbance in any specific plane.

Radiographic changes at the coronal plane in early scoliosis.

The development of structural skeletal changes was evaluated on 132 anteroposterior radiographs of spines from three scoliotic groups with a Cobb angle of up to 30 degrees and a reference control group. Significant wedging of the vertebral bodies and disks at the coronal plane was registered in-curves with a Cobb angle of 4 degrees or more. Asymmetry of the rib-vertebra angle was found in curves with a Cobb angle of 8 degrees or more and was most pronounced in the cranial part of the curves. The early simultaneous occurrence of vertebral and disk wedging suggests the involvement of an extraspinal factor rather than growth disturbance of the vertebral body or of the disk in the early pathomechanism of scoliosis.

Segmental vertebral rotation in early scoliosis.

In order to investigate the development of the vertebral axial rotation in patients with early scoliosis, the vertebral rotation angle (VRA) was quantified on the basis of 132 anteroposterior radiographs obtained from patients with diagnosed or suspected scoliosis. The rotation was measured in the apical vertebra and in the two suprajacent and two subjacent vertebrae. The radiographic material was divided into a control reference group and three scoliotic groups with varying Cobb angle from 4 degrees up to 30 degrees. In the reference group a slight vertebral rotation was significantly more often seen to the right. In the scoliotic groups, the rotation was most pronounced in the apical segments. The mean VRA toward the convex side was significantly increased in the vertebrae just suprajacent to the apex in curves with a Cobb angle of 8 degrees-15 degrees and in the cranial four vertebrae in curves with a Cobb angle of 16 degrees-30 degrees. Atypical vertebral rotation to the opposite side of the major curve was observed in 12.8% of the cases. There was a significant positive correlation between the VRA and the Cobb angle. These results show that a slight VRA to the right is a common feature in the normal spine, and that the VRA increases with progressive lateral deviation of the spine. It is concluded that the coronal plane deformity in early idiopathic scoliosis is accompanied and probably coupled to vertebral rotation in the horizontal plane.

Effects of rib elongation on the spine. I. Distortion of the vertebral alignment in the rabbit.

Elongation of one rib on the right side by 1 cm was achieved in two groups of adult rabbits of different age, by osteotomy and application of a metallic expander. The procedure resulted in immediate deviation of the spine in the frontal and sagittal planes, with moderate scoliosis, convex to the left, and a significant decrease in the normal cervicothoracic lordosis and thoracolumbar kyphosis. Moreover, computed tomography (CT) scanning demonstrated rotation of vertebra about the longitudinal axis relative to the anterior midline of the body, and deviation of the spinous process toward the convex, left side, of the scoliotic deformity. Rib hump developed on the right side--that of the elongated rib. These changes, which occurred simultaneously in the three planes, were less pronounced in the group of older animals. Two weeks after the operation, the distorted configuration of the spine remained unchanged. The observed changes in the alignment of the vertebrae--changes that, except for their direction on the horizontal plane, resembled those associated with idiopathic scoliosis in man--support the earlier proposed link between the early stage of development of this condition and asymmetry of rib growth.

Effects of rib elongation on the spine. II. Correction of scoliosis in the rabbit.

Three intercostal nerves on the right side of growing rabbits were resected partially. From 1 to 3 months later, moderate left-convex thoracic scoliosis with rotation of vertebrae had developed, and the sagittal curvatures of the spine had diminished. In one group of these animals, a mechanically produced increase of 1 cm in the length of one rib on the side of the convexity resulted in an immediate correction of the scoliotic deformity, an improvement that was still evident 3 weeks after the operation. In two other groups of rabbits, a further resection of three intercostal nerves, this time on the left convex side, 1 and 2 months after the first operation, resulted in regression of scoliosis or halted its progression. These results further support a new concept in which the precipitating factor in the development of scoliosis is ascribed to asymmetric longitudinal growth of the ribs. They also suggest that regulation of the rib length could be a promising approach to the effective correction of progressive scoliosis at an early stage in man.

Vascular changes in the chest wall after unilateral resection of the intercostal nerves in the growing rabbit.

In young, growing white New Zealand rabbits the third, fourth, and fifth intercostal nerves were resected anteriorly on the right side. Six months later the animals developed structural left convex scoliosis, with a Cobb angle ranging from 15 to 31 degrees. The vascular structure changes of the anterior chest wall were evaluated by measuring surface temperature and fluorescein intensity of the pectoral muscles, and the capillary density of the pectoral and intercostal muscle and periosteal parts of the ribs after angiography. In five normal control rabbits there was neither scoliotic deformity nor significant differences in the examined vascular variables between the right and left sides. In the animals undergoing resection, the temperature of the pectoral muscle on the side of the denervation--the right side--was significantly increased (p less than 0.05), but the difference was not correlated to the degree of scoliosis. The fluorescence index was significantly greater (p less than 0.05) on the right than on the left side, this difference being fairly strongly correlated to the degree of scoliosis. The capillary densities of the costal periosteum and the intercostal and the pectoral muscle were significantly greater (p less than 0.05) on the right than on the left side, and the difference was positively correlated to the degree of scoliosis. The volume density of the periosteum of the ribs was likewise significantly greater on the right. These results demonstrate that unilateral resection of the intercostal nerves significantly increases the vascularity of the structures on the denervated side of the thorax.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intercostal nerve resection on the longitudinal rib growth in the growing rabbit.

Two, three, or four intercostal nerves with their vasoconstrictive sympathetic fibers were resected on the right side of 15 growing rabbits. Animals submitted to sham operations and intact animals formed two control groups. A scintigraphic study with 99mTc-methylene diphosphonate, performed on the test group 2 months after the resection, showed a significantly greater uptake of the isotope on the right than on the left costochondral junctions (p less than 0.05). Three months later the difference was still larger. There was no such significant difference in the rabbits of the two reference groups. In the rabbits of both these groups, the right and left ribs of each pair were almost equal in length. Of the denervated ribs of the rabbits composing the test group, the right ribs increased in length to a greater extent than the corresponding left ribs. The difference was statistically significant (p less than 0.05). As a consequence of this left-right difference in length, mild thoracic scoliosis convex to the left developed 2 months after the resection. The total weight and volume of the denervated right ribs increased significantly more than those of the corresponding control left ribs (p less than 0.05), but their mineral content per unit of weight or volume showed no significant difference.

Induction of scoliosis in the growing rabbit by unilateral rib-growth stimulation.

Growing rabbits were subjected to surgical resection of the intercostal nerves on the right side, posteriorly or anteriorly. Two other groups of animals were used as sham and as normal controls. Six months after the nerve resection, there was no electromyographic evidence of denervation of the involved muscles. Radiologic examinations revealed progressive development of a curve, convex to the left, in each animal of the two resection groups. Analysis of structural changes by computed tomography showed rotation of the apical vertebra about the longitudinal axis. Rib cage deformity was diagnosed in 82% of the rabbits. The experimental model developed for induction of scoliosis is simple. The surgical procedure involves just one selected and easily recognized anatomic structure, leaving the vertebral structures and their vicinity intact. Reliable analysis of the underlying mechanism of the developing scoliosis is thereby assured.

Excretion of thromboxane A2 and prostacyclin metabolites during treadmill exercise in patients with intermittent claudication.

Platelet activation, with subsequent formation of thromboxane A2 (TxA2), is thought to play a role in the development of arterial occlusion. In patients with severe atherosclerosis of the lower limbs, characterized by leg ulcers and rest pain, the basal formation of TxA2 and prostacyclin (PGI2) is increased. Corresponding data in patients with more moderate atherosclerosis of the lower limbs have not been reported. Since the capacity to physical exercise is not blunted in such patients proper evaluation of their TxA2-PGI2 synthesis should comprise not only assessment of the basal formation, but also TxA2/PGI2 biosynthesis during conditions of elevated cardiovascular activity. To address this, we analysed these eicosanoids in patients with a history of intermittent claudication. Urinary dinor-metabolites of TxB2 and PGI2 (Tx-M and PGI-M, respectively) were estimated by gas chromatography/negative ion-chemical ionization mass spectrometry in samples collected prior to, during and immediately after 20 min of severe treadmill exertion. The basal excretion of Tx-M was 105 +/- 26 pg/mg creatinine. It was not changed during exercise, but increased to 176 +/- 48 pg/mg creatinine (P less than 0.05) during the recovery. The basal excretion of PGI-M was 142 +/- 25 pg/mg creatinine. The PGI-M response to exercise varied from no change at all to a 30-fold increase, without any obvious correlation to experienced leg pain, walking distance or other recorded variables. During the recovery period the outflow of PGI-M was significantly higher than at rest (482 +/- 145 pg/mg creatinine; P less than 0.01). We conclude that in patients with intermittent claudication due to atherosclerosis (1) platelet activation does not occur during the course of the exercise, and (2) vascular prostacyclin formation can be dissociated from of TxA2 synthesis. The observed increase in PGI-M in some of the patients is suggested to reflect tissue ischaemia induced by the lack of adequate hyperaemia during exercise.

The transcapillary exchange of sodium fluorescein in ischaemic limbs measured by fluorescein flowmetry.

The transcapillary exchange of sodium fluorescein in the skin of 36 extremities (19 patients) with arterial occlusive disease was measured using two different ways of analysing the tissue fluorescence, fluorescein flowmetry (FF) and dynamic fluorescein angiography (FA). 7 mg sodium fluorescein/kg body weight was given intravenously. With FF, the transcapillary exchange of sodium fluorescein is expressed in arbitrary units as a fluorescence index. With FA, the time interval from the bolus injection to the first appearance of the fluorescence in the tissue is measured. There was an inverse correlation between pain and fluorescence index. All eight extremities with a fluorescence index of 0.001 density units/s or lower needed amputation, whereas all extremities with higher indices were viable. All extremities requiring amputation had an appearance time of 150 s or more, which contrasted with those remaining viable, having an appearance time of 120 s or less. The results indicate that FF as well as FA are appropriate methods to measure a 'nutritive' transport of solutes in the skin. Theoretically, however, if quantitative values for blood flow are required, we recommend FF, this method being more adequate, since it is influenced both by the fraction of cardiac output distributed to the tissue and by cardiac output itself. If, however, only a prognosis of a limb's viability is needed, FA is sufficient, being easier to perform, only requiring the measurement of the appearance time.