Spinal osteosarcoma.

Although osteosarcoma represents the second most common primary bone tumor, spinal involvement is rare, accounting for 3%-5% of all osteosarcomas. The most frequent symptom of osteosarcoma is pain, which appears in almost all patients, whereas more than 70% exhibit neurologic deficit. At a molecular level, it is a tumor of great genetic complexity and several genetic disorders have been associated with its appearance. Early diagnosis and careful surgical staging are the most important factors in accomplishing sufficient management. Even though overall prognosis remains poor, en-block tumor removal combined with adjuvant radiotherapy and chemotherapy is currently the treatment of choice. This paper outlines histopathological classification, epidemiology, diagnostic procedures, and current concepts of management of spinal osteosarcoma.

Dual lag screw cephalomedullary nail versus the classic sliding hip screw for the stabilization of intertrochanteric fractures. A prospective randomized study.

This study is a randomized prospective study comparing two fracture fixation implants, the extramedullary sliding hip screw (SHS) and the dual lag screw cephalomedullary nail, in the treatment of intertrochanteric femoral fractures in the elderly. One hundred and sixty-five patients with low-energy intertrochanteric fractures, classified as AO/OTA 31A, were prospectively included during a 2-year period (2005-2006). Patients were randomized into two groups: group A included 79 hip fractures managed with sliding hip screws and group B included 86 fractures treated with cephalomedullary nails. Delay to surgery, duration of surgery, time of fluoroscopy, total hospital stay, implant-related complications, transfusion requirements, re-operation details, functional recovery, and mortality were recorded. The mean follow-up was 36 months (24-56 months). The mean surgical time was statistically significantly shorter and fluoroscopy time longer for the group B. No intraoperative femoral shaft fractures occurred. There was no statistically significant difference in the functional recovery score, reoperation, and mortality rates between the 2 groups. A new type of complication, the so-called Z-effect phenomenon, was noticed in the cephalomedullary nail group. There are no statistically significant differences between the two techniques in terms of type and rate of complications, functional outcome, reoperation and mortality rates when comparing the SHS and the cephalomedullary nail for low-energy AO/OTA 31A intertrochanteric fractures. Our data do not support recommendations for the use of one implant over the other.

Effect of two sitting postures on lumbar sagittal alignment and intervertebral discs in runners.

PURPOSE: We evaluated in vivo changes in lumbar lordosis and intervertebral discs in runners and assessed the relationship between these changes and degenerative disc disease in runners with and without a history of low back pain. MATERIALS AND METHODS: Using open upright magnetic resonance (MR) imaging, we prospectively studied changes in lumbar lordosis and intervertebral discs of 25 elite long-distance runners in two sitting postures (neutral and extended) before and after 1 h of running and compared the results with disc height and dehydration/degeneration. Seventeen of the 25 runners had a history of low back pain. RESULTS: After 1 h of running, mean lordosis in neutral posture reduced by 4°; reduction was significant in runners with a history of low back pain. A significant reduction in mean lordosis in extension was not observed. Mean disc height significantly reduced in both postures, without, however, any statistical significance between runners with and without a history low back pain in any posture. Variable degrees of disc dehydration/degeneration were observed in 23 runners (57 discs), more commonly at L5-S1. A significant difference of disc dehydration/degeneration between runners with and without a history of low back pain was not observed. CONCLUSIONS: Intervertebral discs undergo significant strain after 1 h of running that in the long term may lead to low back pain and degenerative disc disease. Runners, especially those with low back pain and degenerative disc disease, should be evaluated after training to preserve the normal lumbar lordosis.

Herpes virus infection can cause intervertebral disc degeneration: a causal relationship?

It has been proposed that intervertebral disc degeneration might be caused by low-grade infection. The purpose of the present study was to assess the incidence of herpes viruses in intervertebral disc specimens from patients with lumbar disc herniation. A polymerase chain reaction based assay was applied to screen for the DNA of eight different herpes viruses in 16 patients and two controls. DNA of at least one herpes virus was detected in 13 specimens (81.25%). Herpes Simplex Virus type-1 (HSV-1) was the most frequently detected virus (56.25%), followed by Cytomegalovirus (CMV) (37.5%). In two patients, co-infection by both HSV-1 and CMV was detected. All samples, including the control specimens, were negative for Herpes Simplex Virus type-2, Varicella Zoster Virus, Epstein Barr Virus, Human Herpes Viruses 6, 7 and 8. The absence of an acute infection was confirmed both at the serological and mRNA level. To our knowledge this is the first unequivocal evidence of the presence of herpes virus DNA in intervertebral disc specimens of patients with lumbar disc herniation suggesting the potential role of herpes viruses as a contributing factor to the pathogenesis of degenerative disc disease.

Intervertebral disc changes after 1 h of running: a study on athletes.

The lumbar spines of 25 long-distance runners were examined using an upright magnetic resonance imaging scanner. All volunteer runners were scanned before and after running for 1 h. Scanning was performed with the runners seated upright (neutral), leaning forwards (flexion) and leaning backwards (extension). All measured discs showed a reduction in disc height after 1 h of running. A significant reduction in disc height was observed in all three body positions (neutral, flexion and extension) after 1 h of running. The results showed that, in flexion, extension and neutral positions, intervertebral discs undergo significant strain after 1 h of running. The lowest disc-height reduction was found at the L5 - S1 space in the neutral position; the same space had the highest percentage of disc degeneration.

Pre-operative versus post-operative gait variability in patients with acute anterior cruciate ligament deficiency.

Change in gait variability at least 6 months after surgical reconstruction of the anterior cruciate ligament (ACL) was assessed in 20 male patients with acute ACL deficiency and compared with pre-operative data and that from 20 healthy male controls. Gait was measured using a triaxial accelerometer and data were analysed by the Gait Evaluation Differential Entropy Method (GEDEM) to determine gait variability. Pain was assessed with a visual analogue scale and functional ability with the Oswestry Disability Index and the International Knee Documentation Committee score. Mean gait variability was significantly lower after than before surgery, with values for the anterior-posterior axis being in the normal range of controls after 6 months, whereas in the mediolateral axis mean gait variability remained significantly higher, indicating that some rotational instability remained in the time-frame of the study. Pain and functional ability scores improved after surgery compared with before surgery. The combination of accelerometry and GEDEM may be a useful orthopaedic tool for the post-operative evaluation of patients who have undergone ACL reconstruction.

The impact of bone mineral density on the degree of curvature of the lumbar spine.

OBJECTIVE: The prevailing perception is that one of the causes of postural deformities is osteoporosis. Nonetheless, studies of the correlation between bone mineral density (BMD) and spinal curvatures have produced contradictory results. This study was undertaken in order to determine whether (BMD) is associated with the curvature of the lumbar spine. METHODS: 105 postmenopausal women, aged 45-76 years (average= 57.3 years), were examined. All the participants underwent DXA scanning and spinal radiography using the same equipment and techniques. Lumbar curvatures were measured using the Cobb method. Subjects were divided according to their T-score into osteoporosis patients (n=54) and controls (n=51). Statistical analysis was performed using one way ANOVA, Mann-Whitney as well as Pearson and Spearman rank correlations. RESULTS: There were no statistically significant correlations between BMD and lumbar curvature angles either in the total sample or in either group individually. Furthermore, these angles were not significantly different between patients with osteoporosis and controls. CONCLUSIONS: The reduction in BMD and the alteration of the lumbar curvature that are observed in elderly individuals are concurrent but not related phenomena. The findings of this study contradict the claim that reduced bone mineral density is the cause of postural deformities.

Pregnancy-related low back pain.

Pregnancy related low back pain is a common complaint among pregnant women. It can potentially have a negative impact on their quality of life. The aim of this article is to present a current review of the literature concerning this issue.By using PubMed database and low back pain, pelvic girdle pain, pregnancy as keywords, abstracts and original articles in English investigating the diagnosis treatment of back pain during pregnancy were searched and analyzedLow back pain could present as either a pelvic girdle pain between the posterior iliac crest and the gluteal fold or as a lumbar pain over and around the lumbar spine. The source of the pain should be diagnosed and differentiated early.The appropriate treatment aims to reduce the discomfort and the impact on the pregnant womans quality of life. This article reveals the most common risk factors, as well as treatment methods, which may help to alleviate the pain. Some suggestions for additional research are also discussed.

Influence of acute anterior cruciate ligament deficiency in gait variability.

The objective of this study was to compare the gait variability of patients with isolated anterior cruciate ligament (ACL) deficiency (experimental group) with that of healthy individuals (control group). The hypothesis was that the gait variability of the experimental group would be higher than the control group. The experimental group consisted of 20 men with an ACL tear and the control group consisted of 20 healthy men without any neurological and/or musculoskeletal pathology or injury. The gait acceleration signal was analysed using the Gait Evaluation Differential Entropy Method (GEDEM). The GEDEM index of the experimental group in the medio-lateral axis was significantly higher than that of the control subjects. A receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of the method and to determine a cut-off entropy value. The GEDEM cut-off value had a 95.6% probability of separating isolated ACL patients from healthy subjects.

Heparin regulates colon cancer cell growth through p38 mitogen-activated protein kinase signalling.

OBJECTIVES: Heparin acts as an extracellular stimulus capable of activating major cell signalling pathways. Thus, we examined the putative mechanisms utilized by heparin to stimulate HT29, SW1116 and HCT116 colon cancer cell growth. MATERIALS AND METHODS: Possible participation of the mitogen-activated protein kinase (MAPK) cascade on heparin-induced HT29, SW1116 and HCT116 colon cancer cell growth was evaluated using specific MAPK cascade inhibitors, Western blot analysis, real-time quantitative PCR and FACS apoptosis analysis. RESULTS: Treatment with a highly specific p38 kinase inhibitor, SB203580, significantly (50-70%) inhibited heparin-induced colon cancer cell growth, demonstrating that p38 MAPK signalling is involved in their heparin-induced proliferative response. This was shown to be correlated with increased (up to 3-fold) phosphorylation of 181/182 threonine/tyrosine residues on p38 MAP kinase. Furthermore, heparin inhibited cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and p53 tumour suppressor gene and protein expression up to 2-fold or 1.8-fold, respectively, and stimulated cyclin D1 expression up to 1.8-fold, in these cell lines through a p38-mediated mechanism. On the other hand, treatment with heparin did not appear to affect HT29, SW1116 and HCT116 cell levels of apoptosis. CONCLUSIONS: This study demonstrates that an extracellular glycosaminoglycan, heparin, finely modulates expression of genes crucial to cell cycle regulation through specific activation of p38 MAP kinase to stimulate colon cancer cell growth.

Gait variability measurements in lumbar spinal stenosis patients: part A. Comparison with healthy subjects.

The objective of this study is to compare the gait variability of patients with lumbar spinal stenosis (experimental group) with healthy individuals (control group). The hypothesis is that the preoperative gait variability of the experimental group is higher than the control group. The experimental group consisted of 35 adults (18 males, 17 females). The subjects of the experimental group suffered exclusively from spinal stenosis. The patients were determined by MRI scans. A tri-axial accelerometer sensor was used for the gait measurement, and differential entropy algorithm was used to quantify the gait acceleration signal. The Oswestry Low Back Pain Questionnaire was used to determine the condition on the day of the measurement. Receiver operating characteristic (ROC) was utilized to assess the diagnostic value of the method and determine a cut-off value. There is a statistically significant difference between gait variability in the control group and the experimental group. ROC analysis determines a cut-off differential entropy value. The cut-off value has a 97.6% probability of separating patients with spinal stenosis from healthy subjects. The Oswestry Low Back Questionnaire is well correlated with the spectral differential entropy values.

Gait variability measurements in lumbar spinal stenosis patients: part B. Preoperative versus postoperative gait variability.

The objective of this study was to assess the gait variability of lumbar spinal stenosis (LSS) patients and to evaluate its postoperative progression. The hypothesis was that LSS patients' preoperative gait variability in the frequency domain was higher than the corresponding postoperative. A tri-axial accelerometer sensor was used for the gait measurement and a spectral differential entropy algorithm was used to measure the gait variability. Twelve subjects with LSS were measured before and after surgery. Preoperative measurements were performed 2 days before surgery. Postoperative measurements were performed 6 and 12 months after surgery. Preoperative gait variability was higher than the corresponding postoperative. Also, in most cases, gait variability appeared to decrease throughout the year.

Accelerometry for evaluation of gait pattern in healthy soccer athletes.

An accelerometer system was used to measure the characteristics of the motion of 133 healthy male soccer athletes in a 30-s walking test and the data obtained were analysed using the gait evaluation differential entropy method (GEDEM). GEDEM processes gait acceleration data and calculates an index that provides a quantitative evaluation of a subject's gait, at low cost and with negligible effect on the subject. The GEDEM index was not significantly correlated with age, body weight, body mass index, or the number of years of active training. The GEDEM value for the anterior-posterior axis showed a small negative statistically significant correlation with height and the vertical axis was moderately and statistically significantly positively correlated with the time spent training per week. The triaxial accelerometry system described here is easy for subjects and testers to use, and enables measurements to be made on the sports field to evaluate an athlete's musculoskeletal condition with respect to gait stability.

Mechanoreceptors of the posterior cruciate ligament.

The mechanical role of the anterior and posterior cruciate ligaments in the passive and functional stability of the knee joint has been well documented. Both these knee joint ligaments contain Ruffini, Pacinian, Golgi and free nerve endings with different capabilities of providing the central nervous system with information regarding movement and position as well as chemical events. The posterior cruciate ligament provides 95% of the restraining force to a posterior tibial displacement, is significantly stronger than the other knee ligaments, and sensory nerve endings are located in the tibia and femoral bone insertions. This report aims to review the anatomy and physiology of the various mechanoreceptors of the posterior cruciate ligament, placing special emphasis on their role in knee joint stability. It concludes that the posterior crude ligament may not only serve as a 'mechanical stabilizer' of the knee joint, but also probably has an important 'sensory function' that should be taken into account when dealing with injuries to it.

Chondroitin sulfate and heparan sulfate-containing proteoglycans are both partners and targets of basic fibroblast growth factor-mediated proliferation in human metastatic melanoma cell lines.

Basic fibroblast growth factor (FGF-2) and its respective tyrosine kinase receptors, form an autocrine loop that affects human melanoma growth and metastasis. The aim of the present study was to examine the possible participation of various glycosaminoglycans, i.e. chondroitin sulfate, dermatan sulfate and heparin on basal and FGF-2-induced growth of WM9 and M5 human metastatic melanoma cells. Exogenous glycosaminoglycans mildly inhibited WM9 cell's proliferation, which was abolished by FGF-2. Treatment with the specific inhibitor of the glycosaminoglycan sulfation, sodium chlorate, demonstrated that endogenous glycosaminoglycan/proteoglycan production is required for both basal and stimulated by FGF-2 proliferation of these cells. Heparin capably restored their growth, and unexpectedly exogenous chondroitin sulfate to WM9 and both chondroitin sulfate and dermatan sulfate to M5 cells allowed FGF-2 mitogenic stimulation. Furthermore, in WM9 cells the degradation of membrane-bound chondroitin/dermatan sulfate stimulates basal growth and even enhances FGF-2 stimulation. The specific tyrosine kinase inhibitor, genistein completely blocked the effects of FGF-2 and glycosaminoglycans on melanoma proliferation whereas the use of the neutralizing antibody for FGF-2 showed that the mitogenic effect of chondroitin sulfate involves the interaction of FGF-2 with its receptors. Both the amounts of chondroitin/dermatan/heparan sulfate and their sulfation levels differed between the cell lines and were distinctly modulated by FGF-2. In this study, we show that chondroitin/dermatan sulfate-containing proteoglycans, likely in cooperation with heparan sulfate, participate in metastatic melanoma cell FGF-2-induced mitogenic response, which represents a novel finding and establishes the central role of sulfated glycosaminoglycans on melanoma growth.

Regulation of hyaluronan and versican deposition by growth factors in fibrosarcoma cell lines.

Versican, a large chondroitin sulphate proteoglycan and hyaluronan (HA), a non-sulphated glycosaminoglycan are major constituents of the pericellular matrix. In many neoplastic tissues, changes in the expression of versican and HA affect tumour progression. Here, we analyse the synthesis of versican and hyaluronan by fibrosarcoma cells, and document how the latter is affected by PDGF-BB, bFGF and TGFB2, growth factors endogenously produced by these cells. Fibrosarcoma cell lines B6FS and HT1080 were utilised and compared with normal lung fibroblasts (DLF). The major versican isoforms expressed by DLF and B6FS cells were V0 and V1. Treatment of B6FS cells with TGFB2 showed a significant increase of V0 and V1 mRNAs. Versican expression in HT1080 cells was not significantly affected by any of the growth factors. In addition, TGFB2 treatment increased versican protein in DLF cells. HA, showed approximately a 2-fold and a 9-fold higher production in DLF cells compared to B6FS and HT1080 cells, respectively. In HT1080 cells, HA biosynthesis was significantly increased by bFGF, whereas, in B6FS cells it was increased by TGFB2 and PDGF-BB. Furthermore, analysis of HA synthases (HAS) expression indicated that HT1080 expressed similar levels of all three HAS isoforms in the following order: HAS2> HAS3> HAS1. bFGF shifted that balance by increasing the abundance of HAS1. The major HAS isoform expressed by B6FS cells was HAS2. PDGF-BB and TGFB2 showed the most prominent effects by increasing both HAS2 and HAS1 isoforms. In conclusion, these growth factors modulated, through upregulation of specific HAS isoforms, HA synthesis, secretion and net deposition to the pericellular matrix.

Chondroitin sulfate prevents platelet derived growth factor-mediated phosphorylation of PDGF-Rbeta in normal human fibroblasts severely impairing mitogenic responses.

Platelet-derived growth factor (PDGF) is a major polypeptide mitogen for cells of mesenchymal origin such as fibroblasts. Chondroitin sulfate chains (CS), which are abundant in the extracellular matrix have been shown to physically interact with PDGF-BB modulating its biological function. The aim of the present study was to examine the involvement of CS on PDGF-BB induced proliferative responses and receptor activation in human lung fibroblasts. The addition of exogenous free CS chains caused a significant downregulation of the PDGF-BB mediated mitogenic and chemotactic responses. Similar results were obtained by the increase of endogenous CS biosynthesis after beta-D-xyloside treatment. Furthermore, removal of the membrane-bound CS chains by selective enzymatic treatment significantly increased the proliferative capacity of human fibroblasts. Analysis of PDGF-R phosphorylation in the presence of CS or beta-D-xyloside, revealed a reduction of PDGF-Rbeta phosphorylation in the tyrosine residue 1021. These results demonstrate, for the first time, that CS either soluble or surface bound downregulates the mitogenic responses of PDGF-BB in normal human lung fibroblasts through the reduction of PDGF-Rbeta phosphorylation.

Balloon kyphoplasty as a single or as an adjunct procedure for the management of symptomatic vertebral haemangiomas.

Vertebral haemangiomas are usually asymptomatic and discovered fortuitously during imaging. A small proportion may develop variable degrees of pain and neurological deficit. We prospectively studied six patients who underwent eight surgical procedures on 11 vertebral bodies. There were 11 balloon kyphoplasties, six lumbar and five thoracic. The mean follow-up was 22.3 months (12 to 36). The indications for operation were pain in four patients, severe back pain with Frankel grade C paraplegia from cord compression caused by soft-tissue extension from a thoracic vertebral haemangioma in one patient, and acute bleeding causing Frankel grade B paraplegia from an asymptomatic vascular haemangioma in one patient. In four patients the exhibited aggressive vascular features, and two showed lipomatous, non-aggressive, characteristics. One patient who underwent a unilateral balloon kyphoplasty developed a recurrence of symptoms from the non-treated side of the vertebral body which was managed by a further similar procedure. Balloon kyphoplasty was carried out successfully and safely in all patients; four became asymptomatic and two showed considerable improvement. Neurological recovery occurred in all cases but bleeding was greater than normal. To avoid recurrence, complete obliteration of the lesion with bone cement is indicated. For acute bleeding balloon kyphoplasty should be combined with emergency decompressive laminectomy. For intraspinal extension with serious neurological deficit, a combination of balloon kyphoplasty with intralesional alcohol injection is effective.

Expression and distribution of N-acetyl and N-glycolylneuraminic acids in secreted and cell-associated glycoconjugates by two human osteosarcoma cell lines.

N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the dominant sialic acids (Sia) in mammals usually found in the non-reducing terminal of oligosaccharide side chains in glycoproteins and glycolipids. Their expression and distribution pattern have been correlated both with the malignant phenotype and tumor grade of human cancers. The aim of the present study was to determine by reversed-phase HPLC method the amounts of Neu5Ac and Neu5Gc as well as their distribution among the culture media and cell surface of MG-63 and Saos-2 human osteosarcoma cell lines of high and low metastatic potential. It was determined that MG-63 cells produce up to 5-fold more total sialic acid as compared with the Saos 2 cells. Neu5Ac accounts for ca 60% of the total sialic acids secreted by MG-63 cells, whereas Neu5Gc is the predominant sialic acid present on the MG-63 cell membrane. Saos 2 cells secrete considerable amounts of Neu5Ac to culture media. The obtained data indicate that the human osteosarcoma cells express both forms of Sia-containing glycoconjugates; the differences in the amounts of each of the two major Sia types and their distribution may be related to their differences in morphology and/or metastatic potentials.

Transforming growth factor-beta as a key molecule triggering the expression of versican isoforms v0 and v1, hyaluronan synthase-2 and synthesis of hyaluronan in malignant osteosarcoma cells.

Versican, a large sized chondroitin-sulphate proteoglycan (PG), and its binding partner, hyaluronan (HA), are extracellular matrix (ECM) components that play an essential role in transformed cell behavior. Expression of certain versican isoforms has been implicated in cell migration and proliferation of cancer cells and, on the other hand, disruption of HA synthesis by inhibiting hyaluronan synthase-2 (HAS2) expression in osteosarcoma cells by suppressing cell proliferation, invasiveness and motility. Considering that growth factors, such as TGF-beta, bFGF and PDGF-BB, are important regulators for the expression of the ECM macromolecules, in this study we examined the effect of these growth factors on the expression of the various versican isoforms, HA synthases as well as HA synthesis by MG-63 osteosarcoma cells and normal human osteoblastic periodontal ligament cells (hPDL). Real-time PCR and metabolic labelling followed by fine HPLC analysis coupled to radiochemical detection were the methods utilized. It was found that, contrary to normal hPDL cells, osteosarcoma MG-63 cells do not constitutively express the versican isoforms V0 and V1. Exogenous addition of TGF-beta2 stimulated the versican transcript levels mainly by forcing osteosarcoma cells to express V1 and V0 isoforms. PDGF-BB and bFGF had only minor effects in these cells. In hPDL cells a strong stimulation of the V3 transcript by all growth factors was observed. TGF-beta2 was also the major stimulator of HAS2 isoform expression as well as hyaluronan synthesis in osteosarcoma cells, while PDGF-BB exerted dominant influence on HAS2 isoform expression and hyaluronan biosynthesis by osteoblasts. The obtained results show for the first time that TGF-beta2 triggers the malignant phenotype pattern of versican and hyaluronan expression in human osteosarcoma cells and indicate that this growth factor may account for the metastatic potential of these cells.