Piriformis muscle syndrome: A cross-sectional imaging study in 116 patients and evaluation of therapeutic outcome.

OBJECTIVES: To increase the clinical awareness of piriformis muscle syndrome (PMs) by reporting cross-sectional imaging findings, the clinical impact of imaging studies and treatment outcome. METHODS: Within a 10-year-period, 116 patients referred for radiological evaluation of clinically suspected PMs, with excluded lumbar pathology related to symptomatology, were prospectively studied with MRI and/or computed tomography (CT). Piriformis muscle (PM), sciatic nerve (SN), piriformis region and sacroiliac joints were evaluated. PMs was categorised into primary/secondary, according to a reported classification system. Treatment decisions were recorded. Outcome was categorised using a 3-point-scale. RESULTS: Seventy-four patients (63.8%) exhibited pathologies related to PMs. Primary causes were detected in 12 and secondary in 62 patients. PM enlargement was found in 45.9% of patients, abnormal PM signal intensity/density in 40.5% and sciatic neuritis in 25.7%. Space-occupying lesions represented the most common related pathology. Treatment proved effective in 5/8 patients with primary and 34/51 patients with secondary PMs. In 34 patients, imaging revealed an unknown underlying medical condition and altered treatment planning. CONCLUSIONS: Secondary PMs aetiologies appear to prevail. In suspected PMs, PM enlargement represented the most common imaging finding and space-occupying lesions the leading cause. Imaging had the potential to alter treatment decisions. KEY POINTS: • In clinically suspected PMs cross-sectional imaging may reveal variable pathology. • Secondary PMs aetiologies appeared to be more common than primary. • PM enlargement represented the most common imaging finding in clinically suspected PMs. • Space-occupying lesions in the piriformis region represented the leading cause of PMs. • In clinically suspected PMs cross-sectional imaging may alter treatment planning.

Impaired clearance of apoptotic cells leads to HMGB1 release in the bone marrow of patients with myelodysplastic syndromes and induces TLR4-mediated cytokine production.

Excessive pro-inflammatory cytokine production in the bone marrow has been associated with the pathogenesis of myelodysplastic syndromes. We herein investigated the involvement of toll-like receptors and their endogenous ligands in the induction/maintenance of the inflammatory process in the marrow of patients with myelodysplastic syndromes. We evaluated the expression of toll-like receptors in marrow monocytes of patients (n=27) and healthy controls (n=25) by flow-cytometry and also assessed the activation of the respective signaling using a real-time polymerase chain reaction-based array. We measured the high mobility group box-1 protein, a toll-like receptor-4 ligand, in marrow plasma and long-term bone marrow culture supernatants by an enzyme-linked immunosorbent assay and we performed cross-over experiments using marrow plasma from patients and controls in the presence/absence of a toll-like receptor-4 inhibitor to evaluate the pro-inflammatory cytokine production by chemiluminescence. We assessed the apoptotic cell clearance capacity of patients' macrophages using a fluorescence microscopy-based assay. We found over-expression of toll-like receptor-4 in patients' marrow monocytes compared to that in controls; this over-expression was associated with up-modulation of 53 genes related to the respective signaling. Incubation of patients' monocytes with autologous, but not with normal, marrow plasma resulted in over-production of pro-inflammatory cytokines, an effect that was abrogated by the toll-like receptor-4 inhibitor suggesting that the pro-inflammatory cytokine production in myelodysplastic syndromes is largely mediated through toll-like receptor-4. The levels of high mobility group box-1 protein were increased in patients' marrow plasma and culture supernatants compared to the levels in controls. Patients' macrophages displayed an impaired capacity to engulf apoptotic cells and this defect was associated with excessive release of high mobility group box-1 protein by dying cells. A primary apoptotic cell clearance defect of marrow macrophages in myelodysplastic syndromes may contribute to the induction/maintenance of the inflammatory process through aberrant release of molecules inducing toll-like receptor-4 such as high mobility group box-1 protein.

Safety and effectiveness of retrorectal presacral approach for lumbosacral axial instrumentation. A clinical study.

This prospective study aimed to quantify the risks and complications associated with AxiaLIF in a series of 29 patients. AxiaLIF is a fusion technique using a percutaneous retrorectal, presacral corridor approach to access the L5-S1 and L4-L5 intervertebral spaces transaxially, through the body of S1 and L5 vertebrae. The fusion rate in the present series was 92% and the reported results ranged from 68% to 100%. The only serious complication in the authors' series was one presacral haematoma (1/29, or 35%). Symptomatic subsidence occurred in the stand alone group, resulting in foraminal stenosis and radiculopathy in two patients (7%) and back pain in one (3.5%). Painful radiolucent halo around the rod was noted in a spondylolytic case (1/29, or 3.5%); it resolved after transpedicular instrumentation. AxiaLIF is a novel truly minimally invasive technique not requiring blood transfusion and can be safely performed as a day surgery. Retroperitoneal haematoma, ureteral and vascular injuries can be avoided by respecting the regional anatomical landmarks as guided by accurate fluoroscopy. Only expanding haematomas may have to be drained. Bowel perforation can be prevented by gently sweeping away the rectum from the sacrum before inserting the guide probe.

Role of receptor for hyaluronic acid-mediated motility (RHAMM) in low molecular weight hyaluronan (LMWHA)-mediated fibrosarcoma cell adhesion.

Hyaluronan (HA) modulates key cancer cell functions through interaction with its CD44 and receptor for hyaluronic acid-mediated motility (RHAMM) receptors. HA was recently found to regulate the migration of fibrosarcoma cells in a manner specifically dependent on its size. Here, we investigated the effect of HA/RHAMM signaling on the ability of HT1080 fibrosarcoma cells to adhere onto fibronectin. Low molecular weight HA (LMWHA) significantly increased (p ≤ 0.01) the adhesion capacity of HT1080 cells, which high molecular weight HA inhibited. The ability of HT1080 RHAMM-deficient cells, but not of CD44-deficient ones, to adhere was significantly decreased (p ≤ 0.001) as compared with control cells. Importantly, the effect of LMWHA on HT1080 cell adhesion was completely attenuated in RHAMM-deficient cells. In contrast, adhesion of RHAMM-deficient cells was not sensitive to high molecular weight HA treatment, which identifies RHAMM as a specific conduit of the LMWHA effect. Western blot and real time-PCR analyses indicated that LMWHA significantly increased RHAMM transcript (p ≤ 0.05) and protein isoform levels (53%, 95 kDa; 37%, 73 kDa) in fibrosarcoma cells. Moreover, Western blot analyses showed that LMWHA in a RHAMM-dependent manner enhanced basal and adhesion-dependent ERK1/2 and focal adhesion kinase (FAK) phosphorylation in HT1080 cells. Utilization of a specific ERK1/2 inhibitor completely inhibited (p ≤ 0.001) LMWHA-dependent adhesion, suggesting that ERK1/2 is a downstream effector of LMWHA/RHAMM signaling. Likewise, the utilization of the specific ERK1 inhibitor resulted in a strong down-regulation of FAK activation in HT1080 cells, which identifies ERK1/2 as a FAK upstream activator. In conclusion, our results suggest that RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways.

Knee joint anterior malalignment and patellofemoral osteoarthritis: an MRI study.

OBJECTIVES: To evaluate patellofemoral congruency measurements on MRI and correlate the findings with severity of ipsilateral osteoarthritis. METHODS: We retrospectively reviewed 650 consecutive knee MRI examinations from 622 patients divided into two age groups: ≤50 and >50 year-old. The femoral sulcus angle (SA) and depth (SD), lateral patellar displacement (LPD), lateral patellofemoral angle (LPFA), tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index as well as the grade of focal cartilage defects (ranging from I to IV) in the patellofemoral region were assessed in each subject on axial and sagittal fat-saturated intermediate-w MR images. RESULTS: A significant difference exists between normal and knees with patellofemoral joint osteoarthritis regarding SA (p = 0.0002 and <0.0001), SD (p = 0.0004 and <0.0001), LPD (p = 0.0014 and 0.0009) and LPFA (p = 0.0002 and 0.0003) in both age groups (≤50 and >50 respectively). Significant correlation was found between grading of cartilage defects and SA (rho = 0.21, p = 0.0001 and 0.443, <0.0001), SD (rho = -0.198, p = 0.0003 and -0.418, <0.0001), LPD (rho = 0.176, p = 0.0013 and 0.251, 0.0002) and LPFA (rho = -0.204, p = 0.0002 and -0.239, 0.0005) in both age groups. CONCLUSIONS: Knee joint anterior malalignment is multivariably associated with patellofemoral osteoarthritis. KEY POINTS: • MRI is an excellent method to evaluate knee alignment and articular cartilage damage. • Significant associations exist between alignment parameters and osteoarthritis of the patellofemoral joint. • The "sulcus angle" and "sulcus depth" were the most valuable osteoarthritic markers.

Spinal cord ischemia after endovascular embolization of a type II endoleak following endovascular aneurysm repair.

BACKGROUND: We report a rare case of severe spinal cord ischemia with neurological consequences in a patient who presented after endovascular treatment of a type II endoleak following endovascular aneurysm repair. METHODS AND RESULTS: An enlarging abdominal aortic aneurysm post-endovascular aneurysm repair was detected owing to a persistent type II endoleak caused by a communication between the iliolumbar and L4 lumbar artery for which the patient underwent supraselective embolization with particles and coils. Immediately after the procedure, the patient experienced an acute onset of neurological symptoms in the right lower limb while limb arterial perfusion remained unaffected. Magnetic resonance imaging-magnetic resonance angiography revealed an acute ischemic process at the L2-L4 level. Further follow-up revealed persistence of the endoleak, and the patient was referred to our institution for open surgical treatment. CONCLUSIONS: To the best of our knowledge, this is the first report of severe spinal cord ischemia after transcatheter embolization of the feeding iliolumbar branches of a type II endoleak. Care must be taken during embolization of the feeding artery of type II endoleaks, which may also supply the spinal cord, to minimize the risk of possible spinal cord ischemia.

Respiratory effects, hemodynamic changes and cement leakage during multilevel cement balloon kyphoplasty.

PURPOSE: The purpose of this study is to evaluate the effects of multilevel balloon kyphoplasty (BK) on blood pressure, blood gases and cement leakage. METHODS: This is a prospective study of 63 patients: 31 were treated for osteoporotic vertebral compressive fractures (OVCF) and 32 for osteolytic tumors (OT). Twenty-six patients were treated at 1 level, 15 at 2, 2 at 3, 6 at 4, 3 at 5, 4 at 6, 5 at 7 and 2 at 8. PPMA was used in 43 patients and calcium phosphate in 20. All patients were treated under general anesthesia with continuous invasive monitoring of hemodynamic changes, arterial blood gases and peripheral and regional cerebral oxygen saturation. RESULTS: Two patients had a transient drop in blood pressure between 21 and 42 % during simultaneous inflation of all four balloons at two levels and three more patients during cement injection (two PMMA, one calcium phosphate). Five patients had a cement leak (7.9 %), which was unrelated to the cement type or number of levels. Blood pressure, end-tidal carbon dioxide partial pressure and arterial oxygen partial pressure decreased statistically, but without any clinical significance after cement insertion. Peripheral and regional cerebral oxygen saturation remained unchanged. One-way ANOVA revealed no difference between these changes when clustered by the groups single level, two levels and three or more levels. CONCLUSION: BK performed under general anesthesia appears to be safe when applied in multiple levels in the same seating provided the balloons are inflated sequentially and not simultaneously and the cement is inserted slowly in a very doughy state. Close monitoring of cardiorespiratory factors is valuable. Its rare circulatory effects are unrelated to the number of levels or the cement type.

Sliding screw implants for extracapsular hip fractures.

Hip fractures are associated with significant mortality and morbidity for the patients, more dependent residual status, and increased socio-economic cost. Many hip-fracture patients experience severe functional impairment, and most never recover their pre-fracture level of function. Current research has sought to identify the most effective treatments to reduce the incidence of hip fractures, improve survival and quality of life, and minimize complications and disability. The treatment of these fractures in the elderly aims to return these people to their pre-fracture mobility and functional level. This article reviews the surgical treatment options for extracapsular hip fractures and discusses their associated advantages, disadvantages, and complications. Two types of implants are currently available: the dynamic hip screw (DHS), and the intramedullary hip nail with one or two sliding screws. In this review, no clear advantage of one implant over another for the treatment of extracapsular hip fractures was evident. Both the DHS and hip nails can be used successfully for the treatment of stable hip fractures; for unstable fractures and low subtrochanteric fractures, hip nails are preferred. Although hip nails are associated with limited exposure, lower blood loss and transfusion requirements, and shorter operative time, complications are more common with hip nails. Long-term survival and function are similar in the two approaches. Hip nails with two sliding screws do not seem to make the difference in clinical practice that is reported in biomechanical studies.

Non-operative treatment of peroneal split syndrome: a case report.

Peroneal split syndrome refers to longitudinal tearing of the peroneus brevis tendon at the level of the retrofibular groove. It is an increasingly recognized, albeit frequently overlooked, cause of lateral ankle pain. Several surgical options have been documented for managing this entity, however there are no reports emphasizing the role of conservative treatment. A 48-year-old male patient presented to our department with persistent lateral ankle and hindfoot pain over the past 9 months, following an inversion injury to his right ankle. Magnetic Resonance Imaging demonstrated a longitudinal split of the peroneus brevis tendon. Following peroneus brevis targeted physical therapy, the patient remains symptom free 34 months after his injury. Diagnostic diligence is required in order to direct treatment to the diseased peroneus brevis tendon, thus avoiding prolonged morbidity. A trial of conservative treatment in lower-demand middle aged patients should be considered.

Heparin plays a key regulatory role via a p53/FAK-dependent signaling in melanoma cell adhesion and migration.

Heparin and its various derivatives affect cancer progression in humans. In this study, we show that heparin uptaken intracellularly by melanoma cells activated a signaling cascade, which in turn inhibited melanoma cell adhesion and migration. The reduced ability of M5 cells to adhere onto the fibronectin (FN) substrate was directly correlated to a decrease in the expression of focal adhesion kinase (FAK), which is a key regulator of melanoma motility. Cell treatment with heparin caused a marked downregulation in FAK expression (P ≤ 0.01). This is followed by an analogous inhibition of both constitutive and FN-induced FAK Y397-phosphorylation (P ≤ 0.01). Moreover, heparin stimulated the p53 expression (P ≤ 0.001) of M5 cells and its increased accumulation in the nucleus. This favors a decrease in FAK promoter activation and explains the reduced FAK transcript and protein levels. In conclusion, the results of this study clearly demonstrate that the action of heparin in the regulation of melanoma cell adhesion and migration involves a p53/FAK/signaling pathway, which may be of importance in molecular targeted therapy of the disease.

Quantitative ultrasound measurements in premature infants at 1 year of age: the effects of antenatal administered corticosteroids.

The aim of this study was to evaluate the effects of antenatally administered glucocorticoids on bone status of preterm infants at 1 year corrected age. The study population consisted of 32 preterm infants with a gestational age of 24-34 weeks. The infants were divided into two groups according to antenatal exposure to corticosteroids. Quantitative ultrasound (QUS) assessment of bone was performed in the study infants at the corrected age of 1 year. Blood levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP) were measured at birth and at 1 year corrected age. Levels of PICP and ICTP were significantly lower at birth in corticosteroid-exposed neonates (P < 0.05). At corrected age of 12 months ICTP levels remained significantly lower in corticosteroid-exposed infants, but we found no significant difference in levels of the bone-formation marker PICP between corticosteroid-exposed and nonexposed infants. In the majority of participant preterm infants bone speed of sound (SOS) was within age-adjusted normal values of full-term infants. There was no significant difference in bone SOS between exposed and nonexposed infants at corrected age of 12 months. There was no correlation between SOS and levels of bone markers. The results of our study indicate that, despite the suppression of fetal bone turnover at birth in corticosteroid-exposed infants, antenatal glucocorticoid treatment seems to have no long-term impact on bone status of preterm infants assessed by QUS complementary to measurement of bone-turnover markers at 1 year corrected age.

Transcript levels of major MMPs and ADAMTS-4 in relation to the clinicopathological profile of patients with lumbar disc herniation.

The involvement of matrix metalloproteinases (MMPs) in both the pathogenesis of intervertebral disc (ID) herniation and the spontaneous regression of herniated ID fragments remains only partially elucidated. The purpose of the present study was to simultaneously examine the transcript levels of a large number of MMPs (-1, -3, -8, -9, -13 and -14) and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs) and to investigate their correlation with the clinicopathologic profile of patients suffering from symptomatic lumbar ID herniation. mRNA expression levels were determined by means of the real-time polymerase chain reaction in 63 herniated and 10 control ID specimens. Our results showed multiple positive correlations among all MMPs and ADAMTS-4 mRNA in herniated samples, indicating their possible synergistic effect in ID herniation. MMP-9 and -13 mRNA levels were significantly elevated in patients with chronic pain, presumably as a consequence of neovascularization and chronic inflammation. Smoking habits were found to have a negative dose-dependent effect on the transcript levels of MMP-3 and MMP-13 and a positive correlation with pain intensity, suggesting an unfavorable role for smoking in the regression process of herniated disc fragments. Our findings provide evidence of the molecular portrait of MMPs and ADAMTS-4 in lumbar ID herniation, as well as of its association with the clinicopathological profile of the patients included in this study, reinforcing the hypothesis of MMPs involvement in the natural history of ID herniation. However, further studies are necessary to elucidate the exact role of MMPs in the resorption process of herniated lumbar discs.

Akt/PKB isoforms expression in the human lumbar herniated disc: correlation with clinical and MRI findings.

Intervertebral disc (IVD) degeneration suggests a complex process influenced by genetics, lifestyle and biomechanics, which accounts for the development of low back pain (LBP) and lumbar radiculopathy, a major cause of musculoskeletal disability in humans. The family of Akt/PKB kinases is a principal mediator in the signal transduction pathways, which contribute to transcriptional regulation, cell growth, proliferation, apoptosis, and survival ability. The purpose of this study was to evaluate the transcriptional profile of the AKT family genes in human herniated discs and the involvement of the PI3K-Akt signaling pathway in human IVD degeneration. Real-time PCR analysis was used to assess the mRNA expression pattern of the three Akt/PKB isoforms in 63 herniated and 10 control disc specimens. Our results showed a significant positive correlation between AKT1 and AKT3 mRNA in herniated discs suggesting a synergistic action between these isoforms in disc herniation. Interestingly, AKT2 mRNA was up-regulated in patients with acute pain during the first 12 months, indicating that AKT2 transcriptional activation may be associated with acute rather than chronic inflammation and phagocytosis. Finally, Akt1/PKB transcription presented a stepwise activation as disc herniation deteriorated. Our findings provide evidence on the transcriptional activation of the Akt/PKB pathway indicating that it is involved in lumbar disc degeneration. There is need for further studies to elucidate the exact role and down-stream signaling action of Akt/PKB isoforms in the pathogenesis of lumbar disc herniation.

Comparison of MR-arthrography and MDCT-arthrography for detection of labral and articular cartilage hip pathology.

OBJECTIVE: To compare the diagnostic ability of MR arthrography (MRa) and MDCT arthrography (CTa) in depicting surgically proven hip labral tears and articular cartilage degradation. MATERIALS AND METHODS: Labral pathology and articular cartilage were prospectively evaluated with MRa and CTa in 14 hips of 10 patients. The findings were evaluated by two independent observers (a musculoskeletal fellow and one senior musculoskeletal radiologist). Sensitivity, specificity, accuracy, and positive predictive value were determined using arthroscopic and open surgery findings as the standard of reference. Interobserver agreement was recorded. All images were assessed for the presence of a labral tear (according to Czerny classification) and for cartilage erosion using a 3 point scale for both methods: 1 = complete visualization-sharp edges, 2 = blurred edges fissuring-partial defects, 3 = exposed bone. The same classification was applied surgically. RESULTS: Disagreement between the senior observer and the fellow observer was recorded in three cases of labral tearing with MRa and six with CTa. Disagreement was also found in four cases of cartilage erosion with both MRa and CTa. The percent sensitivity, specificity, accuracy, and positive predictive value for correctly assessing the labral tear were as follows for MRa/CTa, respectively: 100/15, 50/13, 90/14, and 90/13 (P < 0.05). The same values for cartilage assessment were 63/66, 33/40, 50/57 and 55/66 (P > 0.05). CONCLUSION: Interobserver reproducibility with MRa is very good for labral tearing assessment. MRa is better for assessing labral tears. CTa shows better, but not statistically significant, demonstration of the articular cartilage.

Lateral mass screw complications: analysis of 1662 screws.

STUDY DESIGN: Retrospective, consecutive patient series. OBJECTIVE: To quantify the risks and the complications associated with screw fixation devices of the cervical spine. SUMMARY OF BACKGROUND DATA: The usefulness of lateral mass internal fixation has been well documented in the clinical setting. However, there is a paucity of studies examining the complications associated with these devices in a degenerative clinical setting. METHODS: From 1999 to 2007, 225 consecutive patients underwent posterior cervical fixation using a screw-plate and polyaxial screw-rod implant systems. There were 105 women and 120 men (age range: 45 to 84 y; mean, 68 y). In all patients, the surgical indication was cervical spondylosis with myelopathy. Mean follow-up interval was 18 months (range: 12 to 72 mo). Screw position was evaluated by computed tomography scanning postoperatively in all patients. Clinical and radiographic outcome was assessed at each visit after surgery. RESULTS: Intraoperative complications include fracture of lateral mass in 27 screws placement and nerve irritation in 3 bicortical screws. Early complications include hematoma formation in 2 cases and C5 root palsy in 5 cases after spinal canal decompression. Late complications include pseudarthrosis in 6 cases and screw pull-out in 3 cases. There were no cases of spinal cord or vertebral artery injury, infections, deaths, or adjacent segment disease. All patients had radiographic union, and no patient developed mechanical implant failure requiring removal of instrumentation. Reoperation was required in 14 (6.2%) cases because of nerve injury, hematoma formation, pseudarthrosis, and screw pull-out. CONCLUSIONS: Our clinical findings indicate that lateral mass fixation can be used safely with minimal complications and low rate of morbidity for cervical myelopathy treatment.

Reversal of tetraplegia in a patient with haematogenous cervical epidural abscess.

Pyogenic haematogenous cervical epidural abscess complicated by tetraplegia is an uncommon entity, but its clinical importance overshadows its rarity. Predisposing risk factors for spinal epidural abscess include diabetes, intravenous drug abuse, liver disease, renal failure, malignancy, HIV, infection elsewhere, rheumatoid conditions, trauma and a number of spinal interventions. Lack of recovery and death are much more frequent when complete paralysis exists since more than 24 to 48 hours. Most authors combine decompressive laminectomy and antibiotics. Anterior decompression and needle aspiration are rarely used, the former more specifically in case of anterior abscess formation. A high index of suspicion along with reliance on gadolinium-enhanced MRI is essential to diagnose the pathology and institute appropriate treatment on an individual basis. The authors report on a diabetic male patient who developed a cervical epidural abscess with tetraplegia after dental extraction. He was treated within six hours by one stage anterior/posterior decompression and fusion, with complete recovery.

Spinal chondrosarcoma: a review.

Chondrosarcoma is the third most common primary malignant bone tumor. Yet the spine represents the primary location in only 2% to 12% of these tumors. Almost all patients present with pain and a palpable mass. About 50% of patients present with neurologic symptoms. Chemotherapy and radiotherapy are generally unsuccessful while surgical resection is the treatment of choice. Early diagnosis and careful surgical staging are important to achieve adequate management. This paper provides an overview of the histopathological classification, clinical presentation, and diagnostic procedures regarding spinal chondrosarcoma. We highlight specific treatment modalities and discuss which is truly the most suitable approach for these tumors. Abstracts and original articles in English investigating these tumors were searched and analyzed with the use of the PubMed and Scopus databases with "chondrosarcoma and spine" as keywords.

bFGF induces changes in hyaluronan synthase and hyaluronidase isoform expression and modulates the migration capacity of fibrosarcoma cells.

BACKGROUND: Hyaluronan (HA) a glycosaminoglycan, is capable of transmitting extracellular matrix derived signals to regulate cellular functions. In this study, we investigated whether the changes in HT1080 and B6FS fibrosarcoma cell lines HA metabolism induced by basic fibroblast growth factor (bFGF) are correlated to their migration. METHODS: Real-time PCR, in vitro wound healing assay, siRNA transfection, enzyme digestions, western blotting and immunofluorescence were utilized. RESULTS: bFGF inhibited the degradation of HA by decreasing hyaluronidase-2 expression in HT1080 cells (p=0.0028), increased HA-synthase-1 and -2 expression as we previously found and enhanced high molecular weight HA deposition in the pericellular matrix. Increased endogenous HA production (p=0.0022) and treatment with exogenous high molecular weight HA (p=0.0268) correlated with a significant decrease of HT1080 cell migration capacity. Transfection with siHAS2 and siHAS1 showed that mainly HAS1 synthesized high molecular weight HA regulates HT1080 cell motility. Induced degradation of the HA content by hyaluronidase treatment and addition of low molecular weight HA, resulted in a significant stimulation of HT1080 cells' motility (p<0.01). In contrast, no effects on B6FS fibrosarcoma cell motility were observed. CONCLUSIONS: bFGF regulates, in a cell-specific manner the migration capability of fibrosarcoma cells by modulating their HA metabolism. HA metabolism is suggested to be a potential therapeutic target in fibrosarcoma.

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration.

Parathyroid hormone (PTH) strongly stimulates hyaluronan (HA) synthesis and secretion of both normal and carcinogenic cells of the osteoblastic lineage and improves skeletal microarchitecture. HA, a glycosaminoglycan component of the extracellular matrix (ECM), is capable of transmitting ECM-derived signals to regulate cellular function. In this study, we investigated whether the changes of HA metabolism induced by PTH (1-34) and PTH (7-84) peptides in moderately MG-63 and well-differentiated Saos 2 osteosarcoma cell lines, are correlated to their migration capabilities. Our results demonstrate that intermittent PTH (1-34) treatment significantly (P < or = 0.01) supported the migration of MG-63 cells, increased their HA-synthase-2 (HAS2) expression (P < or = 0.001), and enhanced their high-molecular size HA deposition in the pericellular matrix. Both increased endogenous HA production (P < or = 0.01) and treatment with exogenous high-molecular weight HA (P < or = 0.05) correlated to a significant increase of MG-63 cell migration capacity. Transfection with siHAS2 showed that PTH (1-34), mainly through HAS2, enhanced HA and regulated MG-63 cell motility. Interestingly, continuous PTH (1-34) treatment stimulated both Saos 2 cell HAS2 (P < or = 0.001) and HAS1 (P < or = 0.001) isoform expression inhibited their HYAL2 expression (P < or = 0.001) and modestly (P < or = 0.05) enhanced their migration. Therefore, the PTH (1-34) administration mode appears to distinctly modulate the migratory responses of the MG-63 moderately and Saos 2 well-differentiated osteosarcoma cell lines. Conclusively, the obtained data suggest that there is a regulatory effect of PTH (1-34), in an administration mode-dependent manner, on HA metabolism that is essential for osteosarcoma cell migration.

Case report: subarachnoid anesthesia for kyphoplasty: is anesthesia adequate?

We performed a prospective pilot study of subarachnoid anesthesia for kyphoplasty in 11 nonrandomized patients. Subarachnoid anesthesia was administered at the level of the best palpable intervertebral space below L3. Patients received intrathecally either hyperbaric or plain bupivacaine with or without fentanyl. Five patients experienced pain during the surgical procedure and received supplemental IV analgesia. One patient felt pain from the pressure on the ribs while in the prone position. The remaining patients were comfortable. In no patient was respiratory compromise or deep sedation observed. We conclude that subarachnoid anesthesia may be an adequate technique for kyphoplasty.