Extraforaminal ligament attachments of the thoracic spinal nerves in humans.

An anatomical study of the extraforaminal attachments of the thoracic spinal nerves was performed using human spinal columns. The objectives of the study are to identify and describe the existence of ligamentous structures at each thoracic level that attach spinal nerves to structures at the extraforaminal region. During the last 120 years, several mechanisms have been described to protect the spinal nerve against traction. All the described structures were located inside the spinal canal proximal to the intervertebral foramen. Ligaments with a comparable function just outside the intervertebral foramen are mentioned ephemerally. No studies are available about ligamentous attachments of thoracic spinal nerves to the spine. Five embalmed human thoracic spines (Th2-Th11) were dissected. Bilaterally, the extraforaminal region was dissected to describe and measure anatomical structures and their relationships with the thoracic spinal nerves. Histology was done at the sites of attachment of the ligaments to the nerves and along the ligaments. The thoracic spinal nerves are attached to the transverse process of the vertebrae cranial and caudal to the intervertebral foramen. The ligaments consist mainly of collagenous fibers. In conclusion, at the thoracic level, direct ligamentous connections exist between extraforaminal thoracic spinal nerves and nearby structures. They may serve as a protective mechanism against traction and compression of the nerves by positioning the nerve in the intervertebral foramen.

The polymine spermine regulates osteogenic differentiation in adipose stem cells.

For bone tissue engineering, it is important that mesenchymal stem cells (MSCs) differentiate into osteoblasts. To develop a method for differentiation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) along the osteogenic lineage, we studied the effect of polyamines, which are organic cations implicated in bone growth and development, on differentiation of AT-MSCs. Treatment of goat-derived AT-MSCs with 1,25-dihydroxyvitamin-D3 (1,25(OH)(2)D(3)), which stimulates osteogenic differentiation, for 7 days induced gene expression of the polyamine-modulated transcription factor-1 (PMF-1) and spermidine/spermine N (1)-acetyltransferase (SSAT), which are both involved in polyamine metabolism, suggesting that polyamines are involved in osteogenic differentiation of AT-MSCs. Furthermore, treatment of AT-MSCs with the polyamine spermine-regulated gene expression of runx-2, a transcription factor involved in early stages of osteogenic differentiation, and that of osteopontin, a bone matrix protein expressed in later stages of osteogenic differentiation. Runx-2 gene expression was increased 4 and 14 days after a short 30 min. treatment with spermine, while osteopontin gene expression was only increased 4 days after spermine treatment. Finally, alkaline phosphatase activity, which is intimately involved in the formation of extracellular matrix of bone, was increased 4 weeks after the 30 min.-spermine treatment of AT-MSCs. In conclusion, this study shows for the first time that the polyamine spermine regulates differentiation of AT-MSCs along the osteogenic lineage, which can be used as a new method for differentiation of AT-MSCs along the osteogenic lineage. Therefore, polyamines may constitute a promising tool for bone tissue engineering approaches using AT-MSCs, such as a one-step surgical procedure for spinal interbody fusion.

[Diagnostic image (350). A woman with a swollen knee. Clear cell sarcoma]. / Diagnose in beeld (350). Een vrouw met een gezwollen knie. Heldercellig sarcoom.

A 31-year-old woman presented with a slowly growing mass anterior from the right patella, due to a clear cell sarcoma.

Prostaglandins differentially affect osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells.

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are currently used for bone tissue engineering. AT-MSCs undergoing osteogenic differentiation respond to mechanical loading with increased cyclooxygenase-2 gene expression, a key enzyme in prostaglandin (PG) synthesis. PGs are potent multifunctional regulators in bone, exhibiting stimulatory and inhibitory effects on bone formation and resorption. PGE(2), but not PGI(2) or PGF(2), recruits osteoprogenitors from the bone marrow space and influences their differentiation. We hypothesize that PGE(2), PGI(2), and PGF(2) may differentially regulate osteogenic differentiation of human AT-MSCs. PGE(2), PGI(2), and PGF(2) (0.01-10 microM) affected osteogenic differentiation, but not proliferation of AT-MSCs after 4-14 days. Only PGF(2) (0.01-10 microM) increased alkaline phosphatase (ALP) activity at day 4. PGE(2) (10 microM), PGI(2) (0.01-10 microM), and PGF(2) (10 microM) decreased ALP activity, whereas PGF(2) (0.1 microM) increased ALP activity at day 14. PGF(2) (0.01-0.1 microM) and PGI(2) (0.01 microM) upregulated osteopontin gene expression, and PGF(2) (0.01 microM) upregulated alpha1(I)procollagen gene expression at day 4. PGE(2) and PGF(2) (10 microM) at day 4 and PGF(2) (1 microM) at day 14 downregulated runt-related transcription factor-2 gene expression. We conclude that PGE(2), PGI(2), and PGF(2) differentially affect osteogenic differentiation of AT-MSCs, with PGF(2) being the most potent. Thus, locally produced PGF(2) might be most beneficial in promoting osteogenic differentiation of AT-MSCs, resulting in enhanced bone formation for bone tissue engineering.

[Three previously healthy persons with a stress fracture]. / Drie tevoren gezonde personen met een vermoeidheidsfractuur.

A 42-year-old man presented with a one-month history of pain in his left knee, due to a fracture of the left medial tibia plateau, following a footrace. A 24-year-old man, also a jogger, had had increasing pain in his right lower leg for 4 months, which turned out to be due to a fracture of the posteromedial border of the tibia at the insertion of the flexor digitorum longus muscle. A 35-year-old woman presented with pain in her left foot and ankle that was due to a march fracture of the second metatarsal bone after over 5 hours of intermittent use of the clutch in a traffic jam. In all 3 patients, temporary cessation of the causative activity was sufficient for complete recovery after 3 months. Stress fractures are easily missed on X-rays. Treatment is conservative and consists of the elimination of causative factors to allow adequate healing. In selected cases, a splint or brace may be indicated. Furthermore, certain high risk and displaced fractures should be considered for surgical fixation. Return to the causative activity should be gradual with attention being paid to other potential risk factors.

High rate of failure of impaction grafting in large acetabular defects.

We reviewed the results of 71 revisions of the acetabular component in total hip replacement, using impaction of bone allograft. The mean follow-up was 7.2 years (1.6 to 9.7). All patients were assessed according to the American Academy of Orthopedic Surgeons (AAOS) classification of bone loss, the amount of bone graft required, thickness of the graft layer, signs of graft incorporation and use of augmentation. A total of 20 acetabular components required re-revision for aseptic loosening, giving an overall survival of 72% (95% CI, 54.4 to 80.5). Of these failures, 14 (70%) had an AAOS type III or IV bone defect. In the failed group, poor radiological and histological graft incorporation was seen. These results suggest that impaction allografting in acetabular revision with severe bone defects may have poorer results than have previously been reported.

Evolving gene therapy approaches for osteosarcoma using viral vectors: review.

This review begins with an introduction to the malignant bone tumor, osteosarcoma [OS] and then moves to a discussion of the commonly used vectors for gene transfer. We first briefly highlight non-viral vectors including polymeric and liposomal delivery systems but concentrate predominantly on the 5 leading viral vectors used in cancer gene therapy, specifically retroviruses, adeno-associated viruses, herpes viruses and lentiviruses with the most detailed analysis reserved for adenoviruses. The 3 main strategies for gene therapy in osteosarcoma are next summarized. As part of this review, the several prodrug-converting enzymes utilized in OS suicide gene therapy are examined. The text then turns to a discussion of adenovirus-mediated gene transfer and the need for tumor targeting via transductional or transcriptional approaches. Because of practical problems with use of replication-incompetent viruses in achieving complete tumor kill in vivo, virotherapy utilizing replication competent viruses has come to the fore. This topic is, thus, next reviewed which allows for a natural transition to a discussion of armed therapeutic viruses many of which are conditionally replicating adenoviruses carrying transgenes with established anti-tumor efficacy. We recognize that several other issues have arisen which hamper progress in the field of cancer gene therapy. We, therefore, review viral-induced toxicity in the host and vector delivery issues which have been found to potentially influence safety. We end with a brief perspective including commenting on animal models used in examining delivery strategies for osteosarcoma gene therapy. The challenges remaining are touched upon most especially the need to deal with pulmonary metastatic disease from OS.

Application of polylactides in spinal cages: studies in a goat model.

Spinal cages are currently made of non-resorbable materials, but they only have a temporary function: after fusion, resorption is desirable both from a biological and mechanical point of view. We studied different polylactides in stand-alone condition in a goat model. Cages were made of 100% poly(L-lactic acid) (PLLA) or 70/30 poly(L/DL-Lactic acid) (PLDLLA); titanium served as control. After six months, all titanium cages showed non-unions comparable to that observed in a clinical retrieval, thus showing validity of the goat model. PLLA cages maintained their mechanical integrity for six months, enough to allow fusion. After that, the material resorbed within 48 months without adverse tissue reactions. Bone formation was faster in PLDLLA cages, but these already failed within three months, thus losing their stabilising function: 50% ended in pseudo-arthrosis. Additional internal fixation provided enough stability for fusion (83%). Biocompatibility of both PLLA and PLDLLA was excellent. The long-term results show that PLLA cages can be used for stand-alone interbody fusion, and that PLLA is an improvement over titanium in terms of fusion rate. PLDLLA showed enhanced bone formation, but also earlier failure of the implant. Chances for spinal fusion were better with additional internal fixation.

Different susceptibility of osteosarcoma cell lines and primary cells to treatment with oncolytic adenovirus and doxorubicin or cisplatin.

Despite improvements in treatment regimens for osteosarcoma (OS) patients, survival rate has not increased over the last two decades. New treatment modalities are therefore warranted. Preclinical results with conditionally replicative adenoviruses (CRAds) to treat OS are promising. One type of CRAd that was effective against OS cells is Ad5-Delta24RGD. In other types of cancer, CRAds have been shown to interact synergistically with chemotherapeutic agents. Chemotherapy for OS often includes doxorubicin and cisplatin. Therefore, we explored combination treatment of OS cell lines and primary OS cell cultures with Ad5-Delta24RGD and doxorubicin or cisplatin. On OS cell lines, combination treatment was additive to synergistic. Surprisingly, however, on seven of eight primary OS samples no such combination effects were observed. In contrast, in many cases chemotherapy even inhibited CRAd-mediated cell killing. The inhibitory effect of doxorubicin on Ad5-Delta24RGD in primary OS cells appeared to correlate with slow cell growth rate; reduced viral replication and absence of chemotherapy-induced G2 cell cycle arrest. Our results point to the possibility that, at least for OS, virotherapy and chemotherapy should best not be performed simultaneously. In general, our work underscores the importance of testing new genetic anticancer agents and treatment regimens on primary cancer specimens.

Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells.

Bone morphogenetic proteins (BMPs) initiate, promote, and maintain chondrogenesis and osteogenesis. We hypothesize that BMP-2 induces an osteogenic, and BMP-7 a chondrogenic phenotype in adipose tissue-derived mesenchymal stem cells (AT-MSCs). We compared the effects of a short 15min BMP-2 or BMP-7 (10ng/ml) treatment on osteogenic and chondrogenic differentiation of AT-MSCs. Gene expression was studied 4 and 14 days after BMP-treatment. At day 4 BMP-2, but not BMP-7, stimulated runx-2 and osteopontin gene expression, and at day 14 BMP-7 down-regulated expression of these genes. At day 4 BMP-2 and BMP-7 stimulated biglycan gene expression, which was down-regulated by BMP-7 at day 14. BMP-7 stimulated aggrecan gene expression at day 14. Our data indicate that BMP-2 treatment for 15min induces osteogenic differentiation, whereas BMP-7 stimulates a chondrogenic phenotype of AT-MSCs. Therefore, AT-MSCs triggered for only 15min with BMP-2 or BMP-7 provide a feasible tool for bone and cartilage tissue engineering.

A carbohydrate-rich beverage prior to surgery prevents surgery-induced immunodepression: a randomized, controlled, clinical trial.

BACKGROUND: Fasting before surgery is still common care in a lot of western hospitals. Overnight fasting can induce postoperative insulin resistance. Insulin resistance has been shown to be related to infectious morbidity. It was shown that postoperative insulin resistance can be attenuated by preoperative intake of a clear carbohydrate-rich beverage. The aim of this study was to investigate whether preoperative intake of carbohydrate-rich beverages could postoperatively influence the immune system. METHODS: In this randomized, controlled study, we investigated the effect of surgery on the postoperative immune response in 10 preoperatively fasted patients (control) and 2 groups of 10 patients receiving 2 different carbohydrate-rich beverages preoperatively, by measuring human leukocyte antigen (HLA)-DR expression on monocytes on the day before and on the day after surgery. Furthermore, we studied perioperative fluid homeostasis and preoperative well-being of the patients. RESULTS: HLA-DR expression decreased significantly after surgery in the control group. Patients receiving any of the 2 carbohydrate-rich beverages did not show this postoperative decrease. Fluid homeostasis was not affected in any of the groups, and well-being tended to be better in patients receiving carbohydrate-rich beverages compared with controls. CONCLUSION: This study suggests that preoperative intake of a carbohydrate-rich beverage can prevent surgery-induced immunodepression and thus might reduce the risk of infectious complications.

Bioresorbable polymers: heading for a new generation of spinal cages.

The use of polymer-based bioresorbable materials is now expanding to the realm of spinal interbody fusion. Bioresorbable polymers have important advantages over metals, because they are temporary, much less stiff, and radiolucent. Most promising is a group of alpha-polyesters, in particular polylactide acids (PLAs). Their biocompatibility is excellent, and they have sufficient stiffness and strength to provide initial and intermediate-term stability required for bone healing. However, polylactides have characteristics that make them vulnerable to complications if not properly controlled. Degradation rate strongly depends on polymer type, impurities, manufacturing process, sterilization, device size, and the local environment. The fact that larger implants degrade faster is contra-intuitive, and should be considered in the design process. Also optimal surgical techniques, such as careful bone bed preparation, are required for a successful application of these materials. The purpose of this paper is to highlight the specific properties of these bioresorbable polymers and to discuss their potential and limitations. This is illustrated with early preclinical and clinical data.Bioresorbable cage technology is just emerging: their time-engineered degradation characteristics allow controlled dynamization in interbody applications, facilitating spinal fusion. Their radiolucency improves image assessment of fusion healing. Acceptance and use of bioresorbable implants may increase as further research and clinical studies report on their safety, efficacy, and proper usage.

The effect of the antimicrobial peptide, Dhvar-5, on gentamicin release from a polymethyl methacrylate bone cement.

The objective of this study was to investigate the release mechanism and kinetics of the antimicrobial peptide, Dhvar-5, both alone and in combination with gentamicin, from a standard commercial polymethyl methacrylate (PMMA) bone cement. Different amounts of Dhvar-5 were mixed with the bone cement powders of Osteopal and the gentamicin-containing Osteopal G bone cement and their release kinetics from the polymerized cement were investigated. Additionally, the internal structure of the bone cements were analysed by scanning electron microscopy (SEM) of the fracture surfaces. Secondly, porosity was investigated with the mercury intrusion method and related to the observed release profiles. In order to obtain an insight into the mechanical characteristics of the bone cement mixtures, the compressive strength of Osteopal and Osteopal G with Dhvar-5 was also investigated. The total Dhvar-5 release reached 96% in the 100 mg Dhvar-5/g Osteopal cement, whereas total gentamicin release from Osteopal G reached only 18%. Total gentamicin release increased significantly to 67% with the addition of 50mg Dhvar-5/g, but the Dhvar-5 release was not influenced. SEM showed an increase of dissolved gentamicin crystals with the addition of Dhvar-5. The mercury intrusion results suggested an increase of small pores (< 0.1 microm) with the addition of Dhvar-5. Compressive strength of Osteopal was reduced by the addition of Dhvar-5 and gentamicin, but still remained above the limit prescribed by the ISO standard for clinical bone cements. We therefore conclude that the antimicrobial peptide, Dhvar-5, was released in high amounts from PMMA bone cement. When used together with gentamicin sulphate, Dhvar-5 made the gentamicin crystals accessible for the release medium presumably through increased micro-porosity (< 0.1 microm) resulting in a fourfold increase of gentamicin release.

A bioresorbable molding mesh for impaction grafting revision hip surgery.

Impacted morselized allografts are used to treat bone loss in revision surgery. This technique depends on adequate mechanical support of the graft. Metal support devices function well, but there are disadvantages associated with the use of steel meshes. In this cadaveric, surgical simulation model we investigated the surgical and mechanical suitability of a bioresorbable molding mesh for use in impaction grafting revision surgery. Surgical feasibility was assessed, and mechanical deformation of the mesh during the surgical procedure and postoperative cyclic loading of the specimens were measured with strain gauges. All meshes were surgically usable. The exterior surface deformation of the meshes during the surgical procedure and postoperative mechanical loading did not exceed 4500 microm/m, although the meshes were not damaged in a four-point bending test in which deformations higher than 19,000 microm/m were reached. Therefore, results of this study suggest that this type of bioresorbable mesh seems to have sufficient initial mechanical properties to warrant additional preclinical in vivo study.

Tricalcium-phosphate and hydroxyapatite bone-graft extender for use in impaction grafting revision surgery. An in vitro study on human femora.

Impacted morsellised allografts have been used successfully to address the problem of poor bone stock in revision surgery. However, there are concerns about the transmission of pathogens, the high cost and the shortage of supply of donor bone. Bone-graft extenders, such as tricalcium phosphate (TCP) and hydroxyapatite (HA), have been developed to minimise the use of donor bone. In a human cadaver model we have evaluated the surgical and mechanical feasibility of a TCP/HA bone-graft extender during impaction grafting revision surgery. A TCP/HA allograft mix increased the risk of producing a fissure in the femur during the impaction procedure, but provided a higher initial mechanical stability when compared with bone graft alone. The implications of the use of this type of graft extender in impaction grafting revision surgery are discussed.

Extraforaminal ligament attachments of human lumbar nerves.

STUDY DESIGN: An anatomic study of the extraforaminal attachments of the lumbar spinal nerves was performed using human lumbar spinal columns. OBJECTIVES: To identify and describe the existence of ligamentous structures at each lumbar level that attach lumbar spinal nerves to structures at the level of the extraforaminal region. SUMMARY OF BACKGROUND DATA: During the last 120 years, several mechanisms to protect the spinal nerve against traction have been described. All these structures involved are located in the spinal canal, proximal to the intervertebral foramen. METHODS: Five embalmed human lumbar spines (T12-S1) were used. Bilaterally, the extraforaminal region was dissected to describe and measure anatomic structures and their relationships. Histology was performed with staining on the sites of attachment and along the ligament. RESULTS: The levels T12-L2 show bilaterally 2 ligaments, a superior extraforaminal ligament and an inferior extraforaminal ligament. The superior extraforaminal ligament emerges from the joint capsule of the facet joints and inserts in both, the intervertebral disc and the ventral crista of the intervertebral foramen, passing the spinal nerve laterally. In one specimen on level L2-L3, the superior extraforaminal ligament is not attached to the spinal nerve. The inferior extraforaminal ligament emerges from the intervertebral disc, passing the nerve medially and attaching the spinal nerve. At the levels L2-L5, the inferior extraforaminal ligaments are only attached to the intervertebral disc, not to the joint capsule. Histologically, the ligaments consisted of mainly collagenous structures. CONCLUSION: Ligamentous connections exist between lumbar extraforaminal spinal nerves and nearby structures.

Pregnancy-related pelvic girdle pain (PPP), I: Terminology, clinical presentation, and prevalence.

Pregnancy-related lumbopelvic pain has puzzled medicine for a long time. The present systematic review focuses on terminology, clinical presentation, and prevalence. Numerous terms are used, as if they indicated one and the same entity. We propose "pregnancy-related pelvic girdle pain (PPP)", and "pregnancy-related low back pain (PLBP)", present evidence that the two add up to "lumbopelvic pain", and show that they are distinct entities (although underlying mechanisms may be similar). Average pain intensity during pregnancy is 50 mm on a visual analogue scale; postpartum, pain is less. During pregnancy, serious pain occurs in about 25%, and severe disability in about 8% of patients. After pregnancy, problems are serious in about 7%. The mechanisms behind disabilities remain unclear, and constitute an important research priority. Changes in muscle activity, unusual perceptions of the leg when moving it, and altered motor coordination were observed but remain poorly understood. Published prevalence for PPP and/or PLBP varies widely. Quantitative analysis was used to explain the differences. Overall, about 45% of all pregnant women and 25% of all women postpartum suffer from PPP and/or PLBP. These values decrease by about 20% if one excludes mild complaints. Strenuous work, previous low back pain, and previous PPP and/or PLBP are risk factors, and the inclusion/exclusion of high-risk subgroups influences prevalence. Of all patients, about one-half have PPP, one-third PLBP, and one-sixth both conditions combined. Overall, the literature reveals that PPP deserves serious attention from the clinical and research communities, at all times and in all countries.

Secondary deformities of the shoulder in infants with an obstetrical brachial plexus lesions considered for neurosurgical treatment.

OBJECT: The authors performed a prospective study in which magnetic resonance (MR) imaging was conducted in 26 consecutive infants (mean age 5.6 months, range 2.7-14.5 months) in whom recovery from an obstetric lesion of the brachial plexus had been inadequate in the first 3 months of life. The purpose was to identify early secondary deformations of the shoulder in obstetrical brachial plexus lesions (OBPLs). METHODS: Features of the shoulders were analyzed according to a standardized MR imaging protocol in patients with OBPLs. Measurements were made of the appearance of the glenoid, glenoid version, and the position of the humeral head. The appearance of the glenoid on the affected side was normal in only 11 shoulders. In the remainder it was convex in eight and biconcave in seven cases. The degree of humeral head subluxation was significantly greater (p = 0.001) in affected shoulders than in normal shoulders (152 and 170 degrees, respectively). The presence of abnormal glenoid retroversion and humeral head subluxation increased with age: there was a statistical difference (p = 0.001) between infants younger than 5 months of age and those who were older. CONCLUSIONS: Magnetic resonance imaging demonstrates shoulder-related anatomical and nerve root lesion, allowing evaluation of neural, osseous, and cartilaginous structures in younger children.