The IMpact of Vertical HIV infection on child and Adolescent SKeletal development in Harare, Zimbabwe (IMVASK Study): a protocol for a prospective cohort study.

INTRODUCTION: The scale-up of antiretroviral therapy (ART) across sub-Saharan Africa (SSA) has reduced mortality so that increasing numbers of children with HIV (CWH) are surviving to adolescence. However, they experience a range of morbidities due to chronic HIV infection and its treatment. Impaired linear growth (stunting) is a common manifestation, affecting up to 50% of children. However, the effect of HIV on bone and muscle development during adolescent growth is not well characterised. Given the close link between pubertal timing and musculoskeletal development, any impairments in adolescence are likely to impact on future adult musculoskeletal health. We hypothesise that bone and muscle mass accrual in CWH is reduced, putting them at risk of reduced bone mineral density (BMD) and muscle function and increasing fracture risk. This study aims to determine the impact of HIV on BMD and muscle function in peripubertal children on ART in Zimbabwe. METHODS AND ANALYSIS: Children with (n=300) and without HIV (n=300), aged 8-16 years, established on ART, will be recruited into a frequency-matched prospective cohort study and compared. Musculoskeletal assessments including dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, grip strength and standing long jump will be conducted at baseline and after 1 year. Linear regression will be used to estimate mean size-adjusted bone density and Z-scores by HIV status (ie, total-body less-head bone mineral content for lean mass adjusted for height and lumbar spine bone mineral apparent density. The prevalence of low size-adjusted BMD (ie, Z-scores <-2) will also be determined. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Medical Research Council of Zimbabwe and the London School of Hygiene and Tropical Medicine Ethics Committee. Baseline and longitudinal analyses will be published in peer-reviewed journals and disseminated to research communities.

Muscle quality characteristics of muscles in the thigh, upper arm and lower back in elderly men and women.

PURPOSE: The ratio of fat within skeletal muscle is an important parameter that is indicative of muscle quality, and can be assessed using ultrasonography to measure echo intensity (EI). Muscle EI indicates muscle strength and risk of physical dysfunction; however, this observation was determined following examinations of only selected muscle. The purpose of this study was to investigate the EI characteristics of muscles in several regions in elderly men and women, using physical function tests and serum cholesterol levels. METHODS: Twenty-two men and women (age 78 ± 8 years) participated in this study. The EIs were calculated from rectus femoris (RF), biceps femoris (BF) triceps brachii (TB) and multifidus (MF) using B-mode transverse ultrasound images. Seven functional tests (isometric knee-extension peak torque, functional reach, sit-to-stand, 5-m normal/maximal speed walking, handgrip strength and timed up-and-go) and blood lipid components including adipocytokines were measured in all participants. RESULTS: A statistically significant correlation between EI of the RF, TB and BF was observed (r = 0.46-0.50, P < 0.05), but not between EI of the MF and that of other muscles. EI of muscles of the limbs, which was averaged EI for RF, TB and BF, was negatively correlated with leptin levels (adjusted R2 = 0.27, P < 0.01), and EI of the MF was correlated with muscle mass and performance in the timed up-and-go test (adjusted R2 = 0.61, P < 0.01). CONCLUSION: These results suggest that EI might be influenced by specific parameters depending on the location of the muscle.

Age- and Level-Dependence of Fatty Infiltration in Lumbar Paravertebral Muscles of Healthy Volunteers.

BACKGROUND AND PURPOSE: Normative age-related decline in paravertebral muscle quality is important for reference to disease and risk identification in patients. We aimed to establish age- and vertebral level-dependence of paravertebral (multifidus and erector spinae) muscle volume and fat content in healthy adult volunteers. MATERIALS AND METHODS: In this prospective study multifidus and erector spinae fat signal fraction and volume at lumbar levels L1-L5 were measured in 80 healthy volunteers (10 women and men per decade, 20-62 years of age) by 2-point Dixon 3T MR imaging. ANOVA with post hoc Bonferroni correction compared fat signal fraction and volume among subgroups. Pearson and Spearman analysis were used for correlations (P < .05). RESULTS: Fat signal fraction was higher in women (17.8% ± 10.7%) than men (14.7% ± 7.8%; P < .001) and increased with age. Multifidus and erector spinae volume was lower in women (565.4 ± 83.8 cm(3)) than in men (811.6 ± 98.9 cm(3); P < .001) and was age-independent. No differences in fat signal fraction were shown between the right and left paravertebral muscles or among the L1, L2, and L3 lumbar levels. The fat signal fraction was highest at L5 (women, 31.9% ± 9.3%; men, 25.7% ± 8.0%; P < .001). The fat signal fraction at L4 correlated best with total lumbar fat signal fraction (women, r = 0.95; men, r = 0.92, P < .001). Total fat signal fraction was higher in the multifidus compared with erector spinae muscles at L1-L4 for both sexes (P < .001). CONCLUSIONS: Lumbar paravertebral muscle fat content increases with aging, independent of volume, in healthy volunteers 20-62 years of age. Women, low lumbar levels, and the multifidus muscle are most affected. Further study examining younger and older subjects and the functional impact of fatty infiltrated paravertebral muscles are warranted.

Skeletal morphology and morphometry of the lumbosacral junction in German shepherd dogs and an evaluation of the possible genetic basis for radiographic findings.

The aim of this study was to identify skeletal variations in the lumbosacral junction (LSJ) of the German shepherd dog (GSD) compared with other large breeds. The radiographic traits of the LSJ were investigated in a group of 733 GSDs and a control group of 334 dogs of other breeds that were matched in terms of size. Nine morphological and 17 morphometric traits were recorded and analysed. Furthermore, the possibility of a genetic basis for these radiographic features was evaluated by calculation of genetic variance components. Five of the morphological and 14 of the morphometric traits varied significantly between the GSD group and the control group (P<0.05). Osteochondrosis of the sacral endplate (SOC) had a higher prevalence in the GSDs (10.1%) compared with controls (5.7%). The majority of LSJ degenerative changes recorded from the radiographs occurred in the GSDs. The extent and relative proportion of lumbosacral step formations were greater in the GSD group compared with controls (P<0.001). The lumbosacral vertebral canal height was reduced in the GSD compared with the control dogs (P<0.001) suggesting a primary stenosis. This was accentuated by an abrupt tapering of the vertebral canal at the level of the LSJ indicated by a lumbosacral ratio of 1.51 in the GSD. The skeletal morphology and morphometry of the LSJ in the GSD seem to be different from that found in other large dogs. For multiple traits frequently observed in GSD such as SOC, step formations, and LSJ stenosis, moderate to high non-zero heritabilities were noted. As these features are also assumed to promote lumbosacral disease, selection against these traits is suggested.

An anatomic study of the interspinous space of the lumbosacral spine.

PURPOSE: The purpose of this study is to quantify the interspinous anatomy at the L4/5 and L5/S1 levels. METHODS: One hundred reconstructed computer tomography scans of the lumbosacral spine were reviewed by two separate surgeons. Data were collected from the midline sagittal reconstructed image at the L4-5 and L5-S1 levels. Measurements obtained included the disc angle, anterior and posterior disc height, and maximum interspinous space in both the anterior-posterior and cephalad-caudal directions. The disc height and disc angle were correlated with the interspinous height. RESULTS: The mean age of the patients reviewed was 47 years (range: 16-91; standard deviation: 20). According to our data population, the average length of the interspinous space was larger at the L4-5 level (13 mm) than the L5-S1 level (9 mm). The interspinous height was similar between the two levels. A poor correlation existed between the disc height or disc angle and the interspinous height. There was no correlation between measurements and age. CONCLUSIONS: The interspinous space available, as defined by computer tomography, at the L5/S1 level, is less able to accommodate current interspinous devices compared to the adjacent L4/5 level. The limiting factor is the length of the sacral part of the L5-S1 interspinous space.

Lumbar sagittal shape variation vis-à-vis sex during growth: a 3-year follow-up magnetic resonance imaging study in children from the general population.

STUDY DESIGN: A longitudinal descriptive magnetic resonance imaging study on the changes of the supine lumbar lordosis (SLL), supine sacral slope (SSS), and sagittal wedging of the vertebral body (VB) and intervertebral discs (IVD) in children from the general population. OBJECTIVE: To compare the shape variation during growth of the SLL, SSS, and sagittal wedging of the VB and IVD in boys and girls. SUMMARY OF BACKGROUND DATA: The normal shape variation of the VB, IVD, SLL, and SSS during growth vis-à-vis sex in children from the general population is poorly clarified in the literature as it is usually reported in relation to pathological conditions. METHODS: The SLL, SSS, and sagittal wedging of all lumbar (L1-S1) VBs and IVDs were measured twice from T2-weighted magnetic resonance images of 100 healthy children (51 boys and 49 girls), at mean age 12 to 13 years (t0) and after approximately 3 years (t1) using the iQ-VIEW system (IMAGE Information Systems Ltd., Plauen, Germany). Data for body compositions and pubertal status were collected, and their correlations were analyzed. RESULTS: At baseline (t0), most lumbar VBs were significantly more lordotic in boys (17.1º) than in girls (22.2º); however, girls manifested greater SLL and SSS (45.2º and 33.6º, respectively) than boys (40.7º and 31.4º, respectively), and all IVDs were lordotic, with only the L5-S1 IVD differing between sexes, being more lordotic in girls than in boys (mean difference = 2.8º). At follow-up (t1), SSS became greater in boys (35.7º) than in girls (32.5º), yet all other parameters became independent of sex including all IVDs (except L5-S1) becoming significantly more lordotic, and more so in boys than in girls (total lumbar mean differences being 9.0º and 3.8º, respectively). Increase in boys' heights was correlated with the increase in the L2-L4 lordotic IVD wedging (r = 0.45). Positive correlations were indicated between puberty Tanner stage and individual's height and weight (0.41 < r < 0.45). CONCLUSION: Lumbar VBs decreased their lordotic wedging process during growth, whereas the opposite was observed with the IVDs and SLL, which increased in boys and decreased in girls, becoming independent of sex. The SSS, however, manifested the same process of shape variation, becoming greater in boys than in girls.

Morphometric analysis of lumbosacral canal in human foetuses / Análisis morfométrico del canal lumbosacro en fetos humanos

Lumbosacral part of the spinal canal requires special attention because this is the site commonly involved in spina bifida, tethered cord syndrome and some other pathologies like fatty tumours in the spine, cysts and syrinxes. The diagnosis as well as the treatment of neural tube defects mandates an accurate knowledge of morphometry of lumbosacral vertebral canal. There are various reports on radiological morphometric measurements in human foetuses by various authors but these possess inherent variability due to imaging techniques, patient positioning, observer's measuring techniques and normal and pathological variations. To overcome all these limitations, direct measurements by vernier calliper were preferred. 30 Formalin preserved human foetuses, of all age groups and both sexes, free of congenital craniovertebral anomalies, were obtained from the museum of Dept. of Anatomy, J. N. Medical College AMU Aligarh for the present study. Foetuses were divided into five groups (I-V) based on their gestational ages. Group I foetuses were of less than 17 weeks, II of 17-20 weeks, III of 21-25 weeks, IV of 26-30 weeks and V of more than 30 weeks. Each group contained 6 foetuses having both male and female, 3 each. Morphometric parameters taken into account were length of lumbar canal, maximum transverse diameters of lumbar vertebral canal at different vertebral levels, heights of the posterior surfaces of bodies of all lumbar vertebrae and length of sacral canal. Readings of adjacent groups were compared and results were analyzed by using Student's 't' test. Lumbar canal starts growing in length significantly in group III foetuses onward. There was consistency in the growth of lumbar canal diameters with gestational age at all levels. Heights of vertebral bodies of Ist two lumbar vertebrae showed variability in some adjacent groups. The same in the next three grew constantly with the growth of foetuses. Sacral canal showed variable growth in lengths in different grou...

La porción lumbosacra del canal espinal requiere una atención especial; es un sitio frecuentemente implicado en la espina bífida, el síndrome de médula anclada y algunas otras patologías como tumores de grasa en la columna vertebral, quistes y siringomelia. El diagnóstico y el tratamiento de los defectos del tubo neural requieren de un conocimiento preciso de la morfometría del canal vertebral lumbosacro. Existen diversos informes radiológicos sobre mediciones morfométricas en fetos humanos por parte de diversos investigadores, pero estos poseen una variabilidad inherente debido a las técnicas de imagen, posicionamiento del paciente, técnicas de medición del observador y, las variaciones normales y patológicas. Para superar todas estas limitaciones, para las mediciones directas se utilizó un caliper vernier. 30 fetos humanos conservados en formalina, de todas las edades y de ambos sexos, sin anomalías congénitas craneovertebrales, fueron obtenidos del museo del Departamento de Anatomía, J. N. Facultad de Medicina de la UMA, Aligarh. Los fetos fueron divididos en cinco grupos (I-V) sobre la base de su edad gestacional. El grupo I de fetos fueron los menores de 17 semanas, el II de 17-20 semanas, el III de 21-25 semanas, IV de 26 a 30 semanas, V de más de 30 semanas. Cada grupo contenía 6 fetos de ambos sexos (1:1/H:M)). Los parámetros morfométricos tomados en cuenta fueron la longitud del canal lumbar, el diámetro transversal máximo del canal vertebral lumbar en diferentes niveles, la altura de las superficies posteriores de los cuerpos de todas las vértebras lumbares y la longitud del canal sacro. Las mediciones de los grupos fueron comparadas y analizadas mediante el uso de la prueba de "t". El canal lumbar comenzó a aumentar en longitud significativamente desde el grupo de fetos III en adelante. No hubo consistencia en el crecimiento de los diámetros del canal lumbar con la edad gestacional en todos los niveles. Las alturas de los primeros dos cuerpos verte...

Formation of lamellar cross bridges in the annulus fibrosus of the intervertebral disc is a consequence of vascular regression.

Cross bridges are radial structures within the highly organized lamellar structure of the annulus fibrosus of the intervertebral disc that connect two or more non-consecutive lamellae. Their origin and function are unknown. During fetal development, blood vessels penetrate deep within the AF and recede during postnatal growth. We hypothesized that cross bridges are the pathways left by these receding blood vessels. Initially, the presence of cross bridges was confirmed in cadaveric human discs aged 25 and 53 years. Next, L1-L2 intervertebral discs (n=4) from sheep ranging in age from 75 days fetal gestation to adult were processed for paraffin histology. Mid-sagittal sections were immunostained for endothelial cell marker PECAM-1. The anterior and posterior AF were imaged using differential interference contrast microscopy, and the following parameters were quantified: total number of distinct lamellae, total number of cross bridges, percentage of cross bridges staining positive for PECAM-1, cross bridge penetration depth (% total lamellae), and PECAM-1 positive cross bridge penetration depth. Cross bridges were first observed at 100 days fetal gestation. The overall number peaked in neonates then remained relatively unchanged. The percentage of PECAM-1 positive cross bridges declined progressively from almost 100% at 100 days gestation to less than 10% in adults. Cross bridge penetration depth peaked in neonates then remained unchanged at subsequent ages. Depth of PECAM-1 positive cross bridges decreased progressively after birth. Findings were similar for both the anterior and posterior. The AF lamellar architecture is established early in development. It later becomes disrupted as a consequence of vascularization. Blood vessels then recede, perhaps due to increasing mechanical stresses in the surrounding matrix. In this study we present evidence that the pathways left by receding blood vessels remain as lamellar cross bridges. It is unclear whether the presence of cross bridges in the aging and degenerating intervertebral disc would be advantageous or detrimental, and this question should be addressed by future studies.

Influence of age and sex on lumbar vertebral morphometry determined using sagittal magnetic resonance imaging.

We evaluated age-related changes in the morphometric features of lumbar vertebrae in both sexes using magnetic resonance imaging (MRI). Midsagittal MRI scans of 366 individuals (156 males, 210 females; 25-82 years old) were evaluated retrospectively. The anterior height (H(a)), central height (H(c)), posterior height (H(p)), and anteroposterior diameter (D) of the body of each lumbar vertebra were measured. These measurements were used to calculate three indices, namely, the anterior wedge index (H(a)/H(p)), the biconcavity index (H(c)/H(p)), and the compression index (H(p)/D). The values of each of the three indices for the upper lumbar vertebrae of females were higher than those of the same vertebrae in males. The values of the compression index for all lumbar vertebrae decreased with age in females, whereas in males the compression index of the L1-L4 vertebrae decreased with age. No significant changes were observed in the value of the anterior wedge index in either sex. The biconcavity indices of the L1 and L5 vertebrae decreased with age in males. These results may be useful for evaluating age-related morphological changes that occur in the lumbar vertebrae.

Juvenile xanthogranuloma presenting rapid progression after curettage: a case report with clinicopathological findings.

Juvenile xanthogranuloma is a relatively uncommon benign cutaneous fibrohistiocytic lesion that shows spontaneous regression. We report a case of juvenile xanthogranuloma, which formed a relatively large nodule and rapidly progressed after curettage. A 9-month-old girl had a mass in the skin over the lumbar region of her back that extended to the fascia. The lesion was histologically diagnosed as juvenile xanthogranuloma after total resection of the mass. Although preoperative diagnosis is quite difficult, plastic surgeons should be familiar with this entity. Juvenile xanthogranuloma should be considered in the differential diagnosis of benign tumours and tumour-like lesions in infants. The clinical presentation and histological findings are discussed.

X-irradiation of adult spinal cord increases its capacity to support neurite regeneration in vitro.

Previous in vitro studies have shown that X-irradiation during early postnatal life can change the environment of CNS tissue in later adult life such that it becomes more supportive of neurite regeneration from adult dorsal root ganglion (DRG) neurons than non-irradiated tissue. The question arises whether or not x-irradiation during adult life can alter the CNS environment such that it also becomes more supportive of neurite regeneration. This was investigated by exposing portions of the spinal cord of adult rats to 10, 20 or 40 Gray of X-irradiation and later using this tissue to prepare cryosections suitable for use as a substrate in a cryoculture assay. Fixed cryocultures were immunolabelled using anti-glial fibrillary acidic protein (GFAP) to visualise the tissue sections and anti-growth associated protein (GAP-43) to visualise the regenerating neurites. Tissue sections from sham-irradiated animals and from those irradiated with 10 Gray did not support the regeneration of neurites. However, sections of spinal cords from rats treated with either 20 or 40 Gray of X-irradiation 4 or 32 days prior to sampling were found to support a certain degree of neurite regeneration. It is concluded that X-irradiation of adult CNS tissue can alter its environment such that it becomes more supportive of neurite regeneration and it is speculated that this change may be the result of alterations in the glial cell populations in the post-irradiated tissues.

Breed specific osteological features of the canine lumbosacral junction.

Inefficient facet geometry suggests the lumbosacral junction to be mechanically imperfect in a large number of dogs (especially German Shepherd Dogs) resulting in a significantly higher prevalence of osteophyte formation and increase in the longitudinal extension of the articular surface covering the caudal articular process of the seventh lumbar vertebra. Such osteological features give evidence for lumbosacral craniocaudal translation, were predominantly noticed in combination with axial rotation and are taken to be anatomic risk factors that can predispose to the development of lumbosacral stenosis. The statistically significant relationship between age and the magnitude of the caudal facet inclination angles of the seventh lumbar vertebra in juvenile specimens indicate an affection of the three-dimensional modeling of the immature caudal articular processes by formative stimuli such as body weight and locomotion. However, results additionally indicate an association between the magnitude of these inclination angles and vertebral body dimensions also suggesting a congenital influence on facet geometry.

Perthes' disease and posterior lumbosacral union.

Delayed bone development is common in Perthes' disease, and affected children are usually smaller than normal. Somatosensory evoked potentials (SEP) studied in 25 cases of Perthes' disease were normal. Fifty-four patients with active or healed Perthes' disease were examined. Every child aged less than 8 years showed failure of posterior lumbar and/or sacral fusion. With growth, fusion increased so that at age 14 years 50% had a normal fusion and 50% had spina bifida occulta. At age greater than 16 years, the incidence was similar to that in the general population. In Perthes' disease, growth in fusion of the lumbosacral elements is delayed.

Influence of the erect posture on the development of the lumbosacral region. A comparative study on the lumbosacral junction of the monkey, dog, rabbit and rat.

An animal study was carried out to gain better understanding on the effect of erect posture in the development of the lumbosacral junction. Rhesus monkeys which are able to sit in an upright position were compared with quadrupeds, including rats, rabbits and dogs, whose lumbosacral spines are normally more or less horizontal. The important finding was the presence of the iliolumbar ligament in the rhesus monkey which attached to the last, occasionally the second last, lumbar transverse process and the adjacent iliac wing. A similar ligament was absent in the quadrupeds. We postulate that the stresses created across the lumbosacral junction as a result of the erect posture in the rhesus monkey have played an important role in stimulating the formation of this ligament.

Sheldon's trunk index and the growth of the thoracic and lumbar trunk.

The trunk index (TI), a ratio of the area of the thoracic trunk to that of the lumbar trunk, is measured on a somatotype photograph marked according to defined criteria. Photographs of 82 boys from the Harpenden Growth Study were measured at ages 5 to 18 years, in an order that obscured which photographs were of the same boy at different ages. Remeasurement two months later of 12 boys at each of ages 5, 11, and 18 years showed retest correlations of 0.97 or higher for thoracic and lumbar areas separately and of about 0.95 for their ratio. When 57 boys aged 17 to 20 years were measured by another worker, their TI values correlated 0.90 with those used in this study. Inter-age correlations among the unedited TI values were approximately 0.9 between ages a year apart and declined as age differences increased. Correlations with values at age 18 increased from about 0.7 at age 5 to 0.9 by age 16. Editing was done by remeasuring all values that deviated by more than 0.05 TI units from a regression line based on each subject's total array of values. In the edited data, correlations with TI values at age 18 increased, ranging from 0.8 at age 5 to 0.95 by age 16. Mean TI was quite stable, ranging only between 1.45 and 1.51 for the whole age span, with the lowest values appearing from 11 to 14 years. In 43 of the 59 boys whose series allowed determination of peak height velocity (PHV), a 'TI dip' appeared: one to three TI values fell more than 0.05 TI units below the boy's overall regression line shortly before PHV. Distance and velocity curves are given for growth of the thoracic and lumbar trunk areas. Peak velocity of growth of the lumbar area occurred on average a little earlier than that for the thoracic area; the TI dip was in part a result of this. Alterations of fat distribution as seen by skinfolds probably also contributed. Judging by their individual regression lines, about 80% of the boys showed no more than chance variation from a horizontal slope, their TI neither increasing nor decreasing overall. An additional 10% appeared to show significant slopes only because their series started or ended too near their TI dips. The remaining 10% of boys appeared to show real changes in TI as they grew. Examples of the most extreme changes are shown.