How the lumbrical muscle contributes to placing the fingertip in space: a three dimensional cadaveric study to assess fingertip trajectory and metacarpophalangeal joint balancing.

Three-dimensional fingertip trajectory was examined under different force levels of the lumbrical muscle to clarify the function of the lumbrical muscle in free index finger motion. The metacarpophalangeal joint balancing effect of the lumbrical muscle in the thumb-up position was also examined. The motions of the finger bones were recorded during simulated contraction of flexor digitorum profundus when different forces (0.000-1.960 N) were applied to the lumbrical muscle in cadaveric specimens. The greater the force with which the lumbrical muscle was pulled, the larger the arc formed by the fingertip, and the greater the rebalancing influence on the metacarpophalangeal joint. This result indicates that the lumbrical muscle functions simultaneously to enlarge the fingertip trajectory and to balance the metacarpophalangeal joint against gravity in the axial plane. A 0.980 N force was ideal for maximal finger movement. The lumbrical muscle rebalanced the metacarpophalangeal joint against gravity in the thumb-up position with a force ⩾0.980 N.

Effect of volar angulation of extra-articular distal radius fractures on distal radioulnar joint stability: a biomechanical study.

The relationship between increased volar tilt of the distal radius and distal radioulnar joint stability was examined. Distal radioulnar joint stiffness was recorded at 10° intervals from 10° dorsal angulation to 20° of volar angulation from the anatomical position of the radius. Tests were performed with the intact radioulnar ligament and repeated after partial and then complete sectioning of the radioulnar ligament at the ulnar fovea. With the intact radioulnar ligament, distal radioulnar joint stiffness increased significantly at 10° and 20° of volar angulation. Partial sectioning of the radioulnar ligament resulted in an approximate 10% decrease of distal radioulnar joint stiffness compared with the intact state, but distal radioulnar joint stiffness still increased significantly with greater volar tilt. Complete sectioning of the radioulnar ligament significantly decreased distal radioulnar joint stiffness, and increasing the volar tilt did not result in increased distal radioulnar joint stiffness. These results suggest that volar angulation deformities of the distal radius should be corrected to 10° of volar tilt when the triangular fibrocartilage complex is intact. Level of evidence: N/A.

Arthroscopy of the distal radioulnar joint.

Wrist arthroscopy is now widely indicated for diagnosis and treatment of acute or chronic wrist pain, especially for triangular fibrocartilage complex (TFCC) lesions, as a gold standard. In most cases radiocarpal and midcarpal arthroscopy was performed, while DRUJ arthroscopy has been rarely performed because of its difficulties. Recent anatomic and biomechanical studies demonstrated that the radioulnar ligament (RUL), which is the proximal component of the TFCC facing to the DRUJ, is the primary stabilizer of the distal radioulnar joint (DRUJ). Rupture of the radioulnar ligament (RUL) at the fovea area, where it is the main attaching portion to the ulna and is the isometric point during forearm rotation as the rotation axis passes, is responsible for DRUJ instability. Although physical examination and imaging diagnosis may indicate a foveal detachment of the TFCC, DRUJ arthroscopy is potential for visualizing the RUL at the fovea. Role of DRUJ arthroscopy should be more important not only for diagnosis of rupture of the RUL but also for decision making of treatment option for RUL tear. DRUJ arthroscopy also demonstrates the joint surface of both the sigmoid notch and ulnar head, and the proximal surface of the TFCC.

Pediatric myxopapillary ependymoma treated with subtotal resection and radiation therapy: a case report and review of the literature.

STUDY DESIGN: Case report and review of the literature. OBJECTIVES: Myxopapillary ependymoma (MPE) is a relatively rare glioma that develops from the spinal part of the filum terminale, usually in adulthood. While it is generally benign, MPE can disseminate intraspinally, and this malignant behavior requires a multidisciplinary response with surgery and radiotherapy. We report here a case of MPE occurring in the lumbosacral spine area of an 8-year-old boy. SETTING: Japan, Tokyo. METHODS: We report here a case of MPE, treated with subtotal surgical resection followed by craniospinal irradiation (CSI), in an 8-year-old boy. The patient was referred to our hospital with a 6-month history of severe pain in the lower back and legs, paralysis of the legs and dysuria. Magnetic resonance imaging images showed a large tumor that filled the entire spinal canal below L1. After subtotal resection of the tumor, the pathological findings established a diagnosis of MPE. Since the tumor had perforated its capsule, increasing the risk of intraspinal dissemination, the patient underwent radiotherapy and CSI after surgery. RESULTS: Magnetic resonance images obtained 3 years after the surgery did not show any recurrence of MPE. CONCLUSION: Although tumor resection followed by CSI can be considered an effective strategy for treating a child with MPE, long-term follow-up is necessary to ensure early detection of any local recurrence or dissemination of the tumor, or of post-radiotherapy scoliosis.

TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state.

Chronic inflammation is frequently associated with tumorigenesis in elderly people. By contrast, young people without chronic inflammation often develop tumors considered independent of chronic inflammation but driven instead by mutations. Thus, whether inflammation has a significant role in tumor progression in tumors driven by mutations remains largely unknown. Here we show that TNFα is required for the tumorigenesis of osteosarcoma, the most common tumor in children and adolescents. We show that transplantation of AX osteosarcoma cells, which harbor mutations driving c-Myc overexpression and Ink4a-deficiency, in wild-type mice promotes lethal tumorigenesis accompanied by ectopic bone formation and multiple metastases, phenotypes seen in osteosarcoma patients. Such tumorigenesis was completely abrogated in TNFα-deficient mice. AX cells have the capacity to undergo osteoblastic differentiation; however, that activity was significantly inhibited by TNFα treatment, suggesting that TNFα maintains AX cells in an undifferentiated state. TNFα inhibition of AX cell osteoblastic differentiation occurred through ERK activation, and a pharmacological TNFα inhibitor effectively inhibited both AX cell tumorigenesis and increased osteoblastic gene expression and increased survival of tumor-bearing mice. Lethal tumorigenesis of AX cells was also abrogated in IL-1α/IL-1ß doubly deficient mice. We found that both TNFα and IL-1 maintained AX cells in an undifferentiated state via ERK activation. Thus, inflammatory cytokines are required to promote tumorigenesis even in mutation-induced tumors, and TNFα/IL-1 and ERK may represent therapeutic targets for osteosarcoma.

Is greater than 145{degrees} of deep knee flexion under weight-bearing conditions safe after total knee arthroplasty?: a fluoroscopic analysis of Japanese-style deep knee flexion.

We investigated the characteristics of patients who achieved Japanese-style deep flexion (seiza-sitting) after total knee replacement (TKR) and measured three-dimensional positioning and the contact positions of the femoral and tibial components. Seiza-sitting was achieved after surgery by 23 patients (29 knees) of a series of 463 TKRs in 341 patients. Pre-operatively most of these patients were capable of seiza-sitting, had a lower body mass index and a favourable attitude towards the Japanese lifestyle (27 of 29 knees). According to two-/three-dimensional image registration analysis in the seiza-sitting position, flexion, varus and internal rotation angles of the tibial component relative to the femoral component had means of 148° (SD 8.0), 1.9° (SD 3.2) and 13.4° (SD 5.9), respectively. Femoral surface contact positions tended to be close to the posterior edge of the tibial polyethylene insert, particularly in the lateral compartment, but only 8.3% (two of 24) of knees showed femoral subluxation over the posterior edge. The mean contact positions of the femoral cam on the tibial post were located 7.8 mm (sd 1.5) proximal to the lowest point of the polyethylene surface and 5.5 mm (SD 0.9) medial to the centre of the post, indicating that the post-cam contact position translated medially during seiza-sitting, but not proximally. Collectively, the seiza-sitting position seems safe against component dislocation, but the risks of posterior edge loading and breakage of the tibial polyethylene post remain.

The effects of dorsally angulated distal radius fractures on distal radioulnar joint stability: a biomechanical study.

Relationship between dorsal tilt of the distal radius and distal radioulnar joint stability was examined. Stiffness in dorsopalmar displacement of the radius (distal radioulnar joint stiffness) was recorded at 10° intervals until 30° of dorsal angulation from 10° of palmar tilt. Tests were repeated after partial sectioning of the radioulnar ligament, then after complete sectioning of the radioulnar ligament. All data were compared with control (intact triangular fibrocartilage complex, 10° of palmar tilt). The distal radioulnar joint stiffness in dorsal translation decreased significantly with dorsal tilt 10° and 20° in pronation. Partial sectioning of the radioulnar ligament indicated a decrease of the distal radioulnar joint stiffness in the dorsal translation at neutral tilt to 20° of dorsal tilt in the neutral position and in pronation. Distal radioulnar joint stiffness decreased significantly in both dorsal and palmar translations in all forearm positions at 10° and 20° of dorsal tilt. From these findings, the dorsal angulation of the radius should be corrected to less than 10° of dorsal tilt.

Modic changes in the cervical spine: prospective 10-year follow-up study in asymptomatic subjects.

We conducted a prospective follow-up MRI study of originally asymptomatic healthy subjects to clarify the development of Modic changes in the cervical spine over a ten-year period and to identify related factors. Previously, 497 asymptomatic healthy volunteers with no history of cervical trauma or surgery underwent MRI. Of these, 223 underwent a second MRI at a mean follow-up of 11.6 years (10 to 12.7). These 223 subjects comprised 133 men and 100 women with a mean age at second MRI of 50.5 years (23 to 83). Modic changes were classified as not present and types 1 to 3. Changes in Modic types over time and relationships between Modic changes and progression of degeneration of the disc or clinical symptoms were evaluated. A total of 31 subjects (13.9%) showed Modic changes at follow-up: type 1 in nine, type 2 in 18, type 3 in two, and types 1 and 2 in two. Modic changes at follow-up were significantly associated with numbness or pain in the arm, but not with neck pain or shoulder stiffness. Age (≥ 40 years), gender (male), and pre-existing disc degeneration were significantly associated with newly developed Modic changes. In the cervical spine over a ten-year period, type 2 Modic changes developed most frequently. Newly developed Modic changes were significantly associated with age, gender, and pre-existing disc degeneration.

Primary primitive neuroectodermal tumor of the conus medullaris in an elderly patient: a case report and review of the literature.

Primary spinal primitive neuroectodermal tumors (PNETs) are very rare conditions. Most of these tumors occur in children and young adults. A 63-year-old man with a primary spinal PNET in the conus medullaris from the L1 to L2 level is presented in this report. The optimal treatment of primary spinal PNETs is yet unknown. Surgical resection, radiation therapy, and chemotherapy have been advocated for the treatment of spinal PNET based on PNETs at other sites. However, the outcome is very poor. There are a few reports of cases with long-term survival and no recurrence. In these patients, en bloc resections were performed.

Avulsion of flexor digitorum profundus secondary to recurrent enchondroma.

We report a case of avulsion of the flexor digitorum profundus secondary to recurrent enchondroma. The tumor was curetted with bone grafting of cancellous bone from the distal radius, and the fragment avulsed by the flexor digitorum profundus tendon was fixed to its original site using a pullout suture through the distal phalanx to the nail. The lesion healed and function recovered 6 years after surgery.

Localisation of RA175 (Cadm1), a cell adhesion molecule of the immunoglobulin superfamily, in the mouse testis, and analysis of male infertility in the RA175-deficient mouse.

RA175, a member of the immunoglobulin superfamily, plays an important role in cell adhesion, and RA175 gene-deficient mice (RA175(-/-) ) show oligoastheno-teratozoospermia. To understand the function of RA175, location in the testis and the morphological features of its spermatogenic cells in RA175(-/-) mice were investigated. Immunohistochemical studies revealed that RA175 immunoreactivity was observed on the cell surface of the spermatogenic cells at specific stages. A strong reaction was detected from type A spermatogonia to pachytene spermatocytes at stage IV and from step 6 to step 16 spermatids during spermatogenesis. From pachytene spermatocytes at stage VI to step 4 spermatids, the reaction was not detected by the enzyme-labelled antibody method and was faintly detected by the indirect immunofluorescence method. Abnormal vacuoles in the seminiferous epithelium, showing exfoliation of germ cells, and ultrastructural abnormality of the elongate spermatids were revealed in the RA175(-/-) testes. Other members of the immunoglobulin superfamily such as basigin, nectin-2 and nectin-3, which have an important role in spermatogenesis, were immunohistochemically detected in the RA175(-/-) testis. These observations indicate a unique expression pattern of RA175 in the testis and provide clues regarding the mechanism of male infertility in the testis.

Interstitial lung disease induced by gefitinib and toll-like receptor ligands is mediated by Fra-1.

The role of the AP-1 transcription factor Fra-1 (encoded by Fosl1) in inflammatory responses associated with lung disease is largely unknown. Here, we show that Fra-1 overexpression in mice reduced proinflammatory cytokine production in response to injection of lipopolysaccharide (LPS), a Toll-like receptor (TLR)-ligand. Unexpectedly, Fra-1 transgenic mice died rapidly following LPS treatment, showing severe interstitial lung disease and displaying massive accumulation of macrophages and overproduction of several chemokines, including macrophage chemoattractant protein-1 (MCP-1, encoded by Ccl2). To assess the clinical relevance of Fra-1 in lung pathology, mice were treated with the anticancer drug gefitinib (Iressa), which can lead to interstitial lung disease in patients. Gefitinib-treated mice showed increased Fosl1 and Ccl2 expression and developed interstitial lung disease in response to LPS, endogenous TLR ligands and chemotherapy. Moreover, deletion of Fra-1 or blocking MCP-1 receptor signaling in mice attenuated gefitinib-enhanced lethality in response to LPS. Importantly, human alveolar macrophages showed enhanced LPS-induced FOSL1 and CCL2 expression after gefitinib treatment. These results indicate that Fra-1 is an important mediator of interstitial lung disease following gefitinib treatment.

Surgical treatment of spontaneous posterior interosseous nerve palsy: a retrospective study of 50 cases.

We have reviewed 38 surgically treated cases of spontaneous posterior interosseous nerve palsy in 38 patients with a mean age of 43 years (13 to 68) in order to identify clinical factors associated with its prognosis. Interfascicular neurolysis was performed at a mean of 13 months (1 to 187) after the onset of symptoms. The mean follow-up was 21 months (5.5 to 221). Medical Research Council muscle power of more than grade 4 was considered to be a good result. A further 12 cases in ten patients were treated conservatively and assessed similarly. Of the 30 cases treated surgically with available outcome data, the result of interfascicular neurolysis was significantly better in patients < 50 years old (younger group (18 nerves); good: 13 nerves (72%), poor: five nerves (28%)) than in cases > 50 years old (older group (12 nerves); good: one nerve (8%), poor: 11 nerves (92%)) (p < 0.001). A pre-operative period of less than seven months was also associated with a good result in the younger group (p = 0.01). The older group had a poor result regardless of the pre-operative delay. Our recommended therapeutic approach therefore is to perform interfascicular neurolysis if the patient is < 50 years of age, and the pre-operative delay is < seven months. If the patient is > 50 years of age with no sign of recovery for seven months, or in the younger group with a pre-operative delay of more than a year, we advise interfascicular neurolysis together with tendon transfer as the primary surgical procedure.

Costo-osteochondral graft for post-traumatic osteonecrosis of the radial head in an adolescent boy.

We present a case of post-traumatic osteonecrosis of the radial head in a 13-year-old boy which was treated with costo-osteochondral grafts. A satisfactory outcome was seen at a follow-up of two years and ten months. Although costo-osteochondral grafting has been used in the treatment of defects in articular cartilage, especially in the hand and the elbow, the extension of the technique to manage post-traumatic osteonecrosis of the radial head in a child has not previously been reported in the English language literature. Complete relief of pain was obtained and an improvement in the range of movement was observed. The long-term results remain uncertain.

c-MYC overexpression with loss of Ink4a/Arf transforms bone marrow stromal cells into osteosarcoma accompanied by loss of adipogenesis.

The development of cancer is due to the growth and proliferation of transformed normal cells. Recent evidence suggests that the nature of oncogenic stress and the state of the cell of origin critically affect both tumorigenic activity and tumor histological type. However, this mechanistic relationship in mesenchymal tumors is currently largely unexplored. To clarify these issues, we established a mouse osteosarcoma (OS) model through overexpression of c-MYC in bone marrow stromal cells (BMSCs) derived from Ink4a/Arf (-/-) mice. Single-cell cloning revealed that c-MYC-expressing BMSCs are composed of two distinctly different clones: highly tumorigenic cells, similar to bipotent-committed osteochondral progenitor cells, and low-tumorigenic tripotent cells, similar to mesenchymal stem cells (MSCs). It is noteworthy that both bipotent and tripotent cells were capable of generating histologically similar, lethal OS, suggesting that both committed progenitor cells and MSCs can become OS cells of origin. Shifting mesenchymal differentiation by depleting PPARγ in tripotent MSC-like cells and overexpressing PPARγ in bipotent cells affected cell proliferation and tumorigenic activity. Our findings indicate that differentiation potential has a key role in OS tumorigenic activity, and that the suppression of adipogenic ability is a critical factor for the development of OS.

Microendoscopic resection of lumbar discal cysts.

INTRODUCTION: A lumbar discal cyst is a relatively rare cystic lesion that communicates with lumbar intervertebral discs. Surgical resection of the cyst is the reported treatment of choice. In this study, the authors report the minimally invasive surgical resection of lumbar discal cysts using a microendoscopy. PATIENTS AND METHODS: Seven male patients with lumbar discal cysts underwent microendoscopic resections (mean age: 25.1+/-3.2 years and the mean follow-up period: 27.9 months). During the surgeries, the cysts were subtotally resected in a piecemeal fashion, and the fistulas forming the communications between the cysts and the corresponding intervertebral discs were coagulated using a bipolar coagulator. RESULTS: All the patients obtained relief from their pain after surgery, and no recurrences occurred during a mean follow-up period of 28 months. The mean operation time was 72.6+/-20.2 min, and the mean blood loss was 44.4+/-13.7 grams. No intra- or peri-operative complications were noted in any of the patients. CONCLUSIONS: Microendoscopic resection appears to be a minimally invasive and feasible surgical option for the treatment of lumbar discal cysts.

GRIP1 enhances estrogen receptor alpha-dependent extracellular matrix gene expression in chondrogenic cells.

OBJECTIVE: The role of postmenopause on the pathogenesis of cartilage degeneration has been an open question. We assessed cartilage degeneration in estrogen receptor (ER)alpha null mice and examined the role of glucocorticoid receptor-interacting protein 1 (GRIP1) in the ERalpha-dependent transcription of a type II collagen gene (col2a1) with special reference to a crosstalk with the transforming growth factor (TGF)-beta signaling pathway. METHODS: The vertebral cartilaginous endplate from female ERalpha null mice was subjected to histological analyses. Col2a1 expression of primary chondrocytes (PCs) obtained from ERalpha null mice after 17beta-estradiol (E(2)) and TGF-beta1 stimulation was examined by reverse transcription polymerase chain reaction (RT-PCR). Estrogen response element (ERE) or col2a1 promoter-enhancer luciferase reporter system was used to investigate the crosstalk among ERalpha, GRIP1, and MKK6. Col2a1 expression and glycosaminoglycan (GAG) content were measured in ATDC5 cells treated with GRIP1 small interfering RNA (siRNA). RESULTS: ERalpha deficiency clearly accelerated impairment of the vertebral cartilaginous endplate. E(2) and TGF-beta1 stimulation increased col2a1 expression in PC from wild-type mice, but not that from ERalpha null mice. The same stimulation increased the col2a1 promoter-enhancer reporter activity, and the elevated activity was decreased by dominant-negative ERalpha and p38 mitogen-activated protein kinase (MAPK) inhibitor. GRIP1 increased the E(2)-dependent ERE activation in the presence of ERalpha and constitutive-active MKK6. GRIP1 siRNA repressed col2a1 expression and GAG production in ATDC5 cells. CONCLUSIONS: Crosstalks between ERalpha/GRIP1 and TGF-beta/MKK6/p38 MAPK pathway have protective roles on cartilage metabolism via regulating the extracellular matrices expression. The finding may lead to the development of a novel therapeutic approach for cartilage degeneration.

Tendon entrapment in distal radius fractures.

We retrospectively defined the rate and clinical features of tendon entrapment in 693 consecutive patients with 701 distal radius fractures treated in a single hospital. Eight extensor tendons and one flexor tendon were entrapped. All fractures with extensor tendon entrapment were palmarly displaced (Smith type) or epiphyseal. Flexor tendon entrapment was seen in dorsally angulated (Colles type) epiphyseal fracture. The rate of tendon entrapment in acute distal radius fractures was 1.3%. Extensor tendon entrapment in palmarly displaced fractures is more common.

A role for the aryl hydrocarbon receptor and the dioxin TCDD in rheumatoid arthritis.

OBJECTIVE: Environmental factors are involved in RA pathogenesis and epidemiological studies have suggested that smoking is an environmental risk factor for RA. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the major toxic components in cigarettes. To clarify the biological effects of smoking in RA, we investigated the role of TCDD in RA pathogenesis. METHODS: Human synovial tissue was obtained from RA and OA patients and aryl hydrocarbon receptor (AhR) expression in these tissues was evaluated using immunohistochemistry and real-time PCR. Expression of various cytokines was measured by real-time PCR following stimulation of RA synoviocytes with different concentrations of TCDD. To study the role of AhR, we treated RA synoviocytes with alpha-naphthoflavone, a known AhR antagonist. To evaluate which signal transduction pathways were stimulated by the TCDD-AhR interaction, we used inhibitors of nuclear factor-kappaB (NF-kappaB) and extra-cellular stimulus-activated kinase (ERK). RESULTS: Higher AhR mRNA and protein levels were observed in RA synovial tissue than in OA tissue. TCDD up-regulated the expression of IL-1beta, IL-6 and IL-8 through binding to AhR, and this effect was transmitted via the NF-kappaB and ERK signalling cascades. AhR expression in synovial cells was up-regulated by TNF-alpha. CONCLUSION: TNF-alpha activates AhR expression in RA synovial tissue, and that cigarette smoking and exposure to TCDD enhances RA inflammatory processes. TCDD induces inflammatory cytokines via its association with AhR, resulting in stimulation of the NF-kappaB and ERK signalling cascades. Thus TCDD exposure, such as smoking exacerbates RA pathophysiology.